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SOP Title:- Preparation of Specifications , Standard Testing Procedures and General Testing Procedures

1.         Objective:

To lay down the procedure for Preparation of Specifications, Standard Testing Procedures, General Testing Procedures for Raw Materials, Packing Materials, Miscellaneous Material, Semi-Finished Products, Finished Products and Stability Products.   

 

2.                                 Scope:

This SOP is applicable for Preparation of Specifications, Standard Testing Procedures, General Testing Procedures for Raw Materials, Packing Materials, Miscellaneous Material, Semi-Finished Products, Finished Products and Stability Products in Quality Control Department .

3.                              Responsibility:

3.1        Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Preparation of Specification and Standard Testing Procedure for Raw Materials, Packing Materials and Finished Products in Quality Control Department as per this SOP.

3.2        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	Specifications are to be Prepared as per below Steps:
5.1.1	All Raw Materials, Packing Materials, Miscellaneous Material, Semi-Finished Products, Finished Products and Stability Products specifications are prepared as per IP, BP, USP and EP respective Pharmacopoeias or not referred by any Pharmacopoeial monograph then In-house specification to be prepared.
5.1.2	Additional parameters for Raw Materials like particle size, bulk or tapped density, sieve test etc. to be prepared after successful data generation from last three consecutive batches of respective received materials.
5.1.3	If Raw Material is not referred by any Pharmacopoeial monograph; In-House specification should be prepared.
5.1.4	Generate data based on last three consecutive batches of Raw Material as per manufacturer’s specification.
5.1.5	Additional physical parameters for Finished Products, like length, width, thickness, etc. to be prepared from last three consecutive product validation batches.
5.1.6	If Finished Product is not referred by any Pharmacopoeial monograph; specification should be prepared as per minimum requirement of Drugs & Cosmetic Act.
5.1.7	Generate data based on last three consecutive batches of Finished Products.
5.1.8	All Parameters are prepared based on domestic and export requirements.
5.1.9	For domestic market as per Indian Pharmacopoeia and for Export consignment as per respective export requirement.
5.1.10	All Specification shall be numbered as per respective codes mentioned below.
5.1.11	Raw Material Specification: RM/SPC/XX/NNN/RN             Where      RM:  Raw Material   SPC: Stands for specification                  XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                  NNN: Denotes the three digits serial number (001, 002, 003….)                 RN :   Represents two digit revision number (00,01,02,03….)
5.1.12	Packing Material Specification: PM/SPC/XX/NNN/RN             Where      PM:  Packing Material   SPC: Stands for specification                  XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                 NNN: Denotes the three digits serial number (001, 002, 003….)                 RN :   Represents two digit revision number (00,01,02,03….)
5.1.13	Semi-Finished Specification in case of granules/bulk, filled Capsule, Compressed/uncoated and coated tablets : SF/SPC/NNN/RN             Where      SF  :  Semi – Finished   SPC: Stands for specification                  NNN: Denotes the three digits serial number (001, 002, 003…)                  RN :  Represents two digit revision number (00,01,02,03….)
5.1.14	Finished Product Specification :FP/SPC/NNN/RN             Where      FP :  Finished Product   SPC: Stands for specification                  NNN: Denotes the three digits serial number (001, 002, 003…)                  RN :  Represents two digit revision number (00,01,02,03….)
5.1.15	Refer Annexure No. 04 for preparation of Finished Product Specifications.
5.1.16	Miscellaneous Material Specification :MM/SPC/NNN/RN             Where      MM :  Miscellaneous Material   SPC: Stands for specification                  NNN: Denotes the three digits serial number (001, 002, 003…)                  RN :  Represents two digit revision number (00,01,02,03….)
5.1.17	Stability Study Specification :SS/SPC/NNN/RN             Where      SS :  Stability Study   SPC: Stands for specification                  NNN: Denotes the three digits serial number (001, 002, 003…)                  RN :  Represents two digit revision number (00,01,02,03….)
5.2	Standard Testing Procedures should be prepared as per below steps:
5.2.1	1.       Standard Test Procedures are prepared for Raw Materials, Packing Materials, Semi-Finished Products and Finished Products as per Pharmacopeia requirement.
5.2.2	If the Raw Materials, Packing Material, Miscellaneous Material, Semi-Finished Product and Finished Products are not specified in any Pharmacopoeia then Standard Test Procedure is prepared as per in-House specifications.
5.2.3	Raw Material Standard testing Procedure : RM/STP/XX/NNN/RN Where      RM:  Raw Material   STP: Stands for Standard Testing Procedure                  XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                  NNN: Denotes the three digits serial number (001, 002, 003….)                  RN :   Represents two digit revision number (00,01,02,03….)
5.2.4	Packing Material Standard testing Procedure : PM/STP/XX/NNN/RN Where      PM:  Packing Material   STP: Stands for Standard Testing Procedure                  XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                  NNN: Denotes the three digits serial number (001, 002, 003….)                  RN :   Represents two digit revision number (00,01,02,03….)
5.2.5	Semi-Finished Standard testing Procedure in case of granules/bulk, filled Capsule, Compressed/uncoated and coated tablets :SF/STP/XX/NNN/RN Where      SF :  Semi-Finished Material   STP: Stands for Standard Testing Procedure                  XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                  NNN: Denotes the three digits serial number (001, 002, 003….)                  RN :   Represents two digit revision number (00,01,02,03….)
5.2.6	Finished Product Standard testing Procedure :FP/STP/XX/NNN/RN Where      FP :  Finished Product   STP: Stands for Standard Testing Procedure                  XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                  NNN: Denotes the three digits serial number (001, 002, 003….)                  RN :   Represents two digit revision number (00,01,02,03….)
5.2.7	Miscellaneous Product Standard testing Procedure :MM/STP/XX/NNN/RN Where      MM :  Miscellaneous   STP: Stands for Standard Testing Procedure                  XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                  NNN: Denotes the three digits serial number (001, 002, 003….)                  RN :   Represents two digit revision number (00,01,02,03….)
5.3	General Testing Procedures should be prepared as per below steps:
5.3.1	Numbering system for General Testing Procedures: GM/GTP/XX-YYY             Where     GM:  General Method  GTP: General Testing Procedure                 XX :  Denotes the Pharmacopoeia name (IP, BP, USP, EP,IHS)                                      whom Material complies                 YYY: Denotes the three digits serial number (001, 002, 003….)

  

  

 

6.      Definitions / Abbreviations:

 

 

6.1                   Abbreviations :

 

 

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

 

SOP Title: Analysis and Release of  Semi Finished and Finished Products

1. Objective:

To lay down the procedure for Analysis and Release of Semi Finished and Finished Products.

2. Scope:

This procedure is applicable for Analysis and Release of Semi Finished and Finished Products in

Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Analysis and Release of Semi Finished and Finished Products 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 Analysis and Release of Finished products:
5.1.1	Quality Assurance Personnel is responsible for sampling of finished products and Semi Finished products.
5.1.2	On receipt of the Finished product sample, Supervisor/QC Head shall make entry in the ‘Finished Product Inward Register’.
5.1.3	On receipt of the Semi Finished product sample, Supervisor/QC Head shall make entry in the ‘Semi Finished Product Inward Register’
5.1.4	Supervisor/QC Head shall allocate the Analytical reference Number (A. R. No.) for the samples received as follows:
5.1.5	Assign Analytical Reference Number for Finished Product as “FP/YY/NNN” Where, ‘FP’ stands for ‘Finished Product’. ‘YY’ stands for ‘Last two digits of the current year’. ‘NNN’ stands for ‘Serial number’ i.e. 001, 002 and so on.
5.1.6	Assign Analytical Reference Number for Semi Finished Product as “SF/YY/NNN”. Where, ‘SF’ stands for ‘Semi Finished’. ‘YY’ stands for ‘Last two digits of the current year’. ‘NNN’ stands for ‘Serial number’ i.e. 001, 002 and so on
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.

 

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 equipments 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 “Outside Laboratory Testing” with relevant necessary information.
5.1.12	If tests to be carried out as per IHS, copy of the protocol to be enclosed or scan copy to be mailed.
5.1.13	Analyst should fill in the necessary details on the Analytical work report according to ‘Finished Product Inward Register’ and ‘Semi Finished Product Inward Register’ and start the analysis as per standard testing procedure and specification.
5.1.14	Ensure that all the instruments are calibrated before use.
5.1.15	Analyst should refer to the SOP of instrument before operation and update the instrument operation logs immediately after use.
5.1.16	After the analysis, analyst should hand over the Analytical Work Report to Supervisor/Reviewer for data checking.
5.1.17	If Supervisor/Reviewer observed any discrepancy with analysis or analytical data, he / she should consult to Head of the Department for investigation.

 

5.1.18	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”.
5.1.19	Quality Control Head shall verify and approve the COA and release the Finished Product or Semi Finished Product (if required).
5.1.20	After approval of COA, Supervisor/QC Head shall intimate Quality Assurance Department and hand over the complete report with COA to Quality Assurance Department.
5.1.21	Leftover samples should be destroyed as per SOP “Destruction of Laboratory Waste”.
5.1.22	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.
5.1.23	Supervisor shall initiate investigation as per SOP “Out of Specification” by filling OOS form.
5.1.24	After completion of investigation, categorise the observation as analyst error, reagent error, instrument error or material defect.
5.1.25	Based on detailed investigation and type of error decision shall be taken for release or rejection of the product.
5.1.26	For non conformance of product refer SOP “Control of non-conforming products”.
5.1.27	Update the Finished Product Inward Register or Semi Finished Product Inward Register after release.

6. Definitions / Abbreviations:

• Definitions :
• Finished Product: A finished dosage form, for example a tablet, capsule or solution that contains an active pharmaceutical ingredient, generally but not necessarily, in association with inactive ingredients in a final marketed pack.
• Bulk or Semi-Finished Product: Any products that are obtained during the manufacturing process and that with further processing can become finished products.
• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
COA	Certificate Of Analysis
IHS	In-house Specification
OOS	Out Of Specification
i.e.	That is
A. R. No.	Analytical Reference Number
No.	Number

 

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

SOP Title: Retesting of Raw Materials and Packing Materials

1. Objective:

To lay down the procedure for Retesting of Raw Materials and Packing Materials in Quality Control Department.

2. Scope:

This procedure is applicable for Retesting of previously approved Raw Materials and Packing Materials on the due date of Retest in Quality Control Department .

 

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Retesting of Raw Materials and 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 Retest Raw Materials and Packing Materials.

 

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

 

5.1	Precautions:
5.1.1	Sampling analyst should wear safety nose mask, gloves at the time of sampling.
5.1.2	Do not enter the sampling room when UV light is “ON”.
5.1.3	Sample only one container at a time in a sampling booth.
5.1.4	Do not expose hygroscopic materials for longer time in air as it will absorb the moisture. Cover the samples with double polybag.
5.1.5	Do not expose light sensitive materials for longer time to light as it will degrade the sample. Cover the samples with black polybag.
5.2	Assigning of Retest Date for Raw Materials and Packing Materials:
5.2.1	On release of Raw Materials and Packing Materials enter the Retest Date on the approved labels  and on respective COA as follows:
5.2.2	For Active Raw Materials, Retest Date shall be one year from the date of release.
5.2.3	For Inactive Raw Materials, Retest Date shall be two years from the date of release.
5.2.4	For Packing Materials, Retest Date shall be two years from the date of release.
5.2.5	Example: If the PVC foil is released on 20/08/2022 then the Retest Date shall be 19/08/2024.
5.2.6	While assigning retest date, check that the expiry date of material is not less than the retest date.
5.2.7	If the expiry date of the material is less than the retest due date then the Retest Date shall be same as expiry date.
5.2.8	Example: If the material is released on 25/07/2022, expiry date is 04/2024 then the Retest Date shall be 30/04/2024.
5.2.9	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.
5.3	Sampling Procedure for Raw Materials due for Retest:
5.3.1	Warehouse Head should give “Retest Intimation Slip” as per SOP “Management of Warehouse” prior to 15 day of the Retest Date as per approved label or Raw Material Stock Register.
5.3.2	Warehouse Head should check available quantity of Raw Material in stock and expiry date before raising “Retest Intimation Slip”.
5.3.3	If the quantity is less than 5% of total quantity required for batch or if the material is nearing to expiry in such cases it is discarded raising a deviation note with prior authorisation from Quality Assurance Department.
5.3.4	For sampling containers, sampling devices and sampling procedure refer SOP “Sampling, Analysis and Release or Rejection of Raw Materials”.
5.3.5	On receipt of the test requisition from Warehouse, the sampling analyst or supervisor shall enter all details in “Raw Material Inward Register” and assign the Analytical Reference Number as per SOP “Sampling, Analysis and  Release or Rejection of Raw Materials” and plan for sampling.
5.3.6	Sampling analyst should draw the sample as per sampling plan for respective raw materials.
5.3.7	For Active Materials: 100% sampling should be done as per the specifications of the raw materials.
5.3.8	Inactive Materials: Up to 03 containers, bags or drums, 100% sampling should be done and for consignments with 04 to 100 or more containers/bags/drums, sampling should be done by √n+1 method where ‘n’ is the number of containers/bags/drums received.
5.3.9	For Retest Sample quantity refer the respective Raw Material Specifications. Mark the test on specification which has to be performed during retesting.
5.3.10	During the retesting of raw material only Critical tests shall be carried out which can affects the stability of the material. Refer below test list but not limited to: – A)    Description B)    Loss on drying / Water / Loss on Ignition C)    Assay D)    Related substances / Chromatographic purity E)     Microbiological limit test / Test for Microbiological contamination
	Note:  Above test are just examples. It can be change as per respective specification.
5.3.11	Put the container/bag/drum number on the sample polybag and deface the previously approved label on the container/bag/drum by making cross mark with black marker and affix “UNDER RETEST” (yellow colour) label as per Annexure 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 RETEST” label.
5.3.12	Move all the container/bag/drum of the consignment to the under test area. Affix the “UNDER RETEST” label on all the containers/bags/drums.
5.3.13	If Microbiology testing is required then divide the sample quantity in two polybags i.e. Microbiology sample and Chemical analysis sample as per respective Raw Material Specification.
5.3.14	Sampling analyst should visually take note of physical appearance of material while drawing the sample.
5.3.15	If any discrepancy observed in physical appearance i.e. foreign particles, lumps, colour variation etc. then immediately bring it to the notice of the supervisor.
5.3.16	Keep the analysis sample with “Raw Material Sample for Analysis’ label as per SOP “Sampling, Analysis and Release or Rejection of Raw Materials” in a designated place in Quality Control Laboratory.
5.3.17	Fill up the log entries and affix “To be cleaned” label on sampling accessories as well as on sampling booth.
5.3.18	For cleaning of sampling booth refer to the SOP “Cleaning and Operation of Sampling Booth”.
5.4	Sampling procedure for Packing Materials due for retest:
5.4.1	Warehouse head should give “Retest Intimation Slip” as per SOP “Management of Warehouse” prior to 15 days of the Retest Date as per approved label or Packing Material Stock Register.
5.4.2	On receipt of the “Retest Intimation Slip” from Warehouse, Quality Control Department makes plan for sampling.
5.4.3	For sampling procedure refer SOP “Sampling, Analysis and Release or Rejection of Packing Materials”.
5.4.4	The sampling analyst or Supervisor shall enter all details in “Packing Material Inward Register” and assign the analytical reference number as per “Sampling, Analysis and Release or Rejection of Packing Materials” and plan for sampling.
5.4.5	Sample quantity drawn should be sufficient for single analysis and as per respective Packing Material Specifications. Mark the test on specification which has to be performed during retesting.

 

	During the retesting of Packing material Critical tests shall be carried out which affects the quality of the Packing material. Refer below test list but not limited to: –   1-Description 2-Printed Text 3-VMCH coating 4-Pin hole Test 5-Colour scheme 6-Peel Test 7-Printing 8-Adhesive property 9- Sealing
	Note:  Above test are just examples. It can be change as per respective specification.
5.4.6	Check the consignment as per Retest note for Batch or Lot no, Quantity and any external damages.
5.4.7	Put the rolls/containers/boxes number on the sample polybag and deface the previously approved label on the rolls/containers/boxes by making cross mark with black marker and affix “UNDER RETEST” (yellow colour) label as per Annexure on the container with a stamp “SAMPLED” for those rolls/containers/boxes from which the sample is removed along with container number on each “UNDER RETEST” label.

 

5.4.8	Sampling analyst should visually take note of physical appearance of material while drawing the sample.
5.4.9	If any discrepancy observed in physical appearance then immediately bring it to the notice of the Supervisor.
5.4.10	Keep the analysis sample with “Packing Material Sample for Analysis” label as per SOP “Sampling, Analysis and Release or Rejection of Packing Materials” in a designated place in Quality Control Laboratory.
5.5	Analysis, Release or Rejection of Retest Raw Materials and Packing Materials:
5.5.1	Supervisor/QC Head shall allocate the testing samples to the analysts as per their job responsibility and specialisation.
5.5.2	Analyst should refer respective specification to check the test parameters for retest Raw Materials and Packing Materials and also refer Standard Testing Procedure before initiating the testing.
5.5.3	Carry out retesting for those tests which can demonstrate change in product quality by storing over a period or stability indicating tests which are capable to show material degradation.
5.5.4	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”.
5.5.5	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.
5.5.6	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, by filling “Requisition for Analysis” form as per SOP “Outside Laboratory Testing” with relevant necessary information.
5.5.7	If tests to be carried out as per IHS, copy of the protocol to be enclosed or scan copy to be mailed.
5.5.8	Analyst should fill in the necessary details on the Analytical Work Report according to ‘Raw Material Inward Register’ or ‘Packing Material Inward Register’ and start the analysis as per Standard Testing Procedure and Specification.
5.5.9	Ensure that all the Instruments are calibrated before use.
5.5.10	Analyst should refer to the SOP of Instrument before operation and update the Instrument operation logs immediately after use.
5.5.11	Analyst should refer to the SOP of Instrument before operation and update the Instrument operation logs immediately after use.
5.5.12	After the analysis, analyst should hand over the Analytical Work Report to Supervisor/Reviewer analyst for data checking.
5.5.13	If Supervisor/Reviewer observed any discrepancy with analysis or analytical data, he / she should consult to Head of the Department for investigation.
5.5.14	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”.
5.5.15	Quality Control Head shall verify and approve the COA and release the retest materials.
5.5.16	Incase of Raw Materials, after approval of COA, analyst should prepare “APPROVED” labels (green colour) as per SOP “Sampling, Analysis and Release or Rejection of Raw Materials” with approved by signature on it.
5.5.17	Incase of Packing Materials, after approval of COA, analyst should prepare “APPROVED” labels (green colour) as per SOP “Sampling, Analysis and Release or Rejection of Packing Materials” with approved by signature on it.
5.5.18	Affix “APPROVED” labels on top of the “UNDER RETEST” label on all containers in such a way that the “UNDER RETEST” word on the label should be covered but the details on the Under Retest label should be seen.

 

5.5.19	No need to mention potency/Assay and Water/LOD/LOI on approved label in case of Inactive Materials.
5.5.20	Photocopy of the approved COA shall be provided to the Warehouse Department if required.
5.5.21	Leftover samples should be destroyed as per SOP “Destruction of Laboratory Waste”.
5.5.22	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.
5.5.23	Supervisor shall initiate investigation as per SOP “Out of Specification” by filling OOS form.
5.5.24	After completion of investigation, categorise the observation as analyst error, reagent error, Instrument error or material defect.
5.5.25	If material has major defect that can affect product quality or out of respective Pharmacopoeial monograph or IHS then material should be rejected.
5.5.26	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 as per SOP .
5.5.27	Photocopy of Rejected COA shall be provided to Warehouse. Photocopy is not necessary if software (ERP) is used for material inventory or control.
5.5.28	Rejected Material shall be disposed as per SOP “Destruction of residues and line rejects”.

 

6. Definitions / Abbreviations:

• Definitions:
• Retest Period: Retest Period is the period of time during which the Raw Materials and Packing Materials can be considered to remain within specifications, and therefore acceptable for use in the manufacture of a given drug product, provided that it has been stored under defined conditions. After this period, these should be retested for compliance with the specifications before use.
• Expiry Date: The date at which a product is no longer potent or of therapeutic value, determined by The date for a drug estimated for its shelf life with proper storage in sealed containers away from harmful and variable factors like heat and humidity.

 

• Abbreviations:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
WH	Warehouse
UV	Ultra Violet
√n+1	Under route of n = numbers of containers, bags, drums
COA	Certificate of Analysis
%	Percentage
i.e.	That is
A. R. No	Analytical Reference Number
IHS	Inhouse Specification
OOS	Out Of Specification
ERP	Enterprise Resource Procedures
PVC	Poly Vinyl Chloride
PVDC	Poly Vinyl Dichloride

 

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

 

SOP Title: Allotment of Job Responsibilities in Quality Control Department

1. Objective:

To lay down the procedure for Allotment of Job Responsibilities in Quality Control Department.

2. Scope:

This procedure is applicable for Allotment of Job Responsibilities of Analyst, Executive, Supervisor, and Manager in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Allotment of Job Responsibilities 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	General Responsibilities:- All Quality Control Staff
5.1.1	Keep Laboratory neat and clean.
5.1.2	Careful usage of organisation resources without any wastage.
5.1.3	To identify hazards and safety issues in Laboratory and inform Head of the Department.
5.1.4	Keep good and healthy working culture in the Laboratory.
5.1.5	Keep all the documents/materials at respective places after use.
5.1.6	Switch off lights and instruments whenever not required.
5.1.7	Minimise wastage of papers.
5.1.8	Maintain Good Laboratory Practices in Laboratory.
5.1.9	Always think about environment hazards before generating waste.
5.1.10	Do not perform any job without proper training.
5.1.11	Read the Instrument/Equipment SOP’s and Standard Testing Procedures carefully before starting the analysis.
5.2	Responsibilities of Quality Control Head/ Quality Control Manager:
5.2.1	Quality Control Head/ Manager is responsible for the overall monitoring of the Department.
5.2.2	Maintaining Good Laboratory Practices.
5.2.3	Taking care of trouble shooting during day to day analysis.
5.2.4	Maintaining good rapport with all other Departments and outside parties.
5.2.5	Keeping control on new product analysis and development.
5.2.6	Discussion of quality problem, if any with higher managements.
5.2.7	Evaluation of stability data.
5.2.8	Monitoring and evaluation of validation samples and data.
5.2.9	Preparation and updating of SOP’s as per requirement and current guidelines.
5.2.10	Investigation of OOS/Incidents/Deviations.
5.2.11	Conducting trainings to quality control staff.
5.2.12	Impact evaluation of OOS/Incidents/Deviations.
5.2.13	Ensuring readiness  for non-regulatory, regulatory and internal audits all the time.
5.2.14	Release and Approval of Raw Material/Packing Material/Finished Product/In process Sample reports and COA on time.
5.2.15	Impact evaluation of change control.
5.2.16	To identify new manpower requirement.
5.2.17	To identify new Instrument/Equipment requirement.
5.2.18	To ensure safety of Quality Control staff in the Department.
5.2.19	To monitor and evaluate performance of Quality Control staff.
5.2.20	Any other responsibility assigned by the management as situation demand.
5.2.21	To maintain training records up to date.
5.3	Responsibilities of Supervisor/Group Leader/Executive/Assistant Manager:
5.3.1	Maintaining Good Laboratory Practices.
5.3.2	Taking care of trouble shooting during day to day analysis.
5.3.3	Discussion of quality problem, if any with higher managements.
5.3.4	Evaluation of stability data.
5.3.5	Monitoring and evaluation of validation samples and data.
5.3.6	Preparation and updating of SOP’s as per requirement and current guidelines.
5.3.7	Review of analytical reports of Raw Material/Packing Material/ In process Sample / Finished Product and Microbiology reports.
5.3.8	Review of Instrument/Equipment usage log books.
5.3.9	Daily work planning to the analysts.
5.3.10	Review of new documents like Standard Testing Procedures, Specifications, Protocols etc.
5.3.11	Checking of all GMP records in the Laboratory.
5.3.12	Initiation of change control.
5.3.13	Monitoring safety in Quality Control Department.
5.3.14	Checking calibration reports and preventive maintenance records.
5.3.15	Conducting trainings to Quality Control staff.
5.3.16	To verify training records of Quality Control staff.
5.3.17	To maintain training records up to date.
5.3.18	Updation of sample inward records for Raw Material/Packing Material/Finished Product/In process Sample/Stability samples.
5.3.19	Preparation and monitoring of Calibration/AMC schedule in Laboratory.
5.3.20	Investigation of OOS/Incidents/Deviations.
5.3.21	Maintaining all time readiness for non-regulatory, regulatory and internal audits.
5.3.22	To ensure safety of Quality Control staff in the Department.
5.3.23	Any other responsibility assigned by the management as situation demand.
5.3.24	To ensure proper storage and handling of Chemicals/Media/Solvents/ Poisonous chemicals/Reference standards/Working standards as per SOP.
5.4	Responsibilities of Analyst/Officer/Microbiologist:
5.4.1	To follow Good Laboratory Practices.
5.4.2	Sampling and analysis of Raw Materials/Packing Materials and maintaining records.
5.4.3	Analysis of In process Samples/Finished Products and maintaining records.
5.4.4	Preparation of Control Samples of Raw and Packing Materials.
5.4.5	Stability Study Analysis as per plan.
5.4.6	Sampling and analysis of water and water validation as per plan.
5.4.7	Maintaining records of Instrument/Equipment usage log.
5.4.8	Discussing any quality problems with Quality Control Head/Manager.
5.4.9	Cleaning, maintenance and calibration of laboratory Instruments/Equipments as per schedule.
5.4.10	Preparation of Reagents/Indicators/Volumetric Solutions and maintaining records.
5.4.11	Procurement, Storage and Handling of Media/Chemicals/Solvents for analysis and maintaining stock and consumption records.
5.4.12	To follow safety precautions during work.
5.4.13	To maintain training records up to date.
5.4.14	To maintain online documentation.
5.4.15	All time readiness for non-regulatory, regulatory and internal audits.
5.4.16	To complete analysis and reporting within stipulated time period.
5.4.17	To file OOS/Deviation/Incident.
5.4.18	To follow and work as per standard operating procedure.
5.4.19	Daily reporting to quality control head/supervisor.
5.4.20	Careful usage of organisation resources without any wastage.
5.4.21	Any other responsibility assigned by the management as situation demand.
5.4.22	Review of analytical reports.
5.4.23	Execute daily work planning as per Standard Testing Procedure, Specification, Pharmacopoeia etc.
5.4.24	Preparation of new documents like Standard Testing procedures, Specifications, Protocols etc.
5.4.25	Preparation, handling and storage of Reference standards/Working standards as per SOP.
5.4.26	Daily up keeping of laboratory.
5.4.27	Environmental monitoring and maintaining records.
5.4.28	Maintenance of cultures, preparation of subcultures, serial culture dilution, decontamination and maintaining records.
5.4.29	Minimum inhibitory concentration, validation of disinfectants used and maintaining records.
5.4.30	Growth promotion of media as per SOP and maintaining records.
5.4.31	After allotment of Job Responsibilities, update ‘Employee Job Responsibilities’ as per Annexure

 

6. Definitions / Abbreviations:

• Definitions:
• Abbreviations:

 

Abbreviation	Expansion
OOS	Out Of Specification
AMC	Annual Maintenance Call
GMP	Good Manufacturing Practices
Etc.	Excetra

 

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

 

Title: Calibration of Glassware’s

1. Objective:

To lay down the Procedure for Calibration of Volumetric Glassware. 

    

2. Scope:

This procedure is applicable for Verification or Calibration of Volumetric Glassware used in Quality Control Department.

 

3. Responsibility:
   • Quality Control Department: To prepare and review the SOP. To follow the Procedure for Verification or Calibration of Volumetric Glassware 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	Procedure for Verification or Calibration of Glassware :
5.1.1	On receipt of volumetric glassware it should be calibrated before use.
5.1.2	It is not safe to assume that the volume delivered by or contained in any volumetric apparatus is exactly the amount indicated by the calibration mark.
5.1.3	Recalibration is usually performed by weighing the amount of water delivered by or contained in the volumetric apparatus.
5.1.4	The mass is then converted to the desired volume using the tabulated density of Water : Volume = mass / density
5.1.5	The volume occupied by a given mass of liquid varies with temperature. The volume of the device that holds the liquid with 25 °C with temperature has been chosen as the normal temperature for calibration of many volumetric glassware.
5.1.6	1.       Glass is a fortunate choice for volumetric ware as it has a relatively small coefficient of thermal expansion; a glass vessel which holds 1.00000 L at 15°C, holds 1.00025 L at 25°C.
5.1.7	2.       A correction for this expansion must frequently be applied during calibration procedures.
5.1.8	3.       If the correction is small enough it may be ignored.
5.1.9	Temperature °C Density (g/ml) Temperature °C Density (g/ml) 20 0.99823 24 0.99733 21 0.99802 25 0.99707 22 0.99780 26 0.99681 23 0.99757 27 0.9965162 Thermal expansion chart
5.2	Cleaning of glassware before calibration:
5.2.1	Cleaning of volumetric glassware is necessary before calibration, to remove any contaminants for accurate calibration.
5.2.2	4.       Two or three rinsing with tap water, a moderate amount of agitation and two or three rinsing with distilled water are generally sufficient and drying at 60±5°c for one to two hours.
5.2.3	Remove the glassware from the drier and cool them at room temperature.
5.3	Calibration of Glassware’s:
	A.              Calibration or Verification of volumetric flasks:
5.3.1	The Volumetric Flask is used to prepare Standard Solutions or dilution.
5.3.2	Most of these flasks   are calibrated To-Contain (TC) a given volume of liquid.
5.3.3	Weigh and note the weight of previously dried and cooled empty volumetric flask at ≈ 25°C.
5.3.4	Fill the weighted volumetric flask up to mark with boiled and cooled purified water at ≈ 25°C and record the weight.
5.3.5	If any droplets of solvent adhere to the neck, use a piece of tissue to blot these out.
5.3.6	Calculate the weight of the water occupied by volumetric flask and divide with density of water or theoretical as 0.99707 g/ml at 25°C.
5.3.7	Record the data in Glassware Verification /Calibration record as per Annexure No. 01.
	B.              Calibration or Verification of graduated and volumetric pipettes:
5.3.8	Drainage rates from  the  pipette  must  be carefully controlled so as to leave a uniform and reproducible film along the inner glass surface.
5.3.9	To fill the pipette, insert it vertically in the liquid, with the tip near the bottom of the container.
5.3.10	Apply suction to draw the liquid above the mark.
5.3.11	Quickly place a fore finger over the end of the stem.
5.3.12	Withdraw the pipette from the liquid and use a dry paper to wipe off the stem.
5.3.13	Now place the tip of the pipette against the container from which the liquid has been withdrawn and drain the excess liquid such that the meniscus is at the graduation mark.
5.3.14	Record the weight of a cleaned and dried beaker at ≈ 25°C.
5.3.15	Allow the liquid to flow out of the pipette freely into the weighed beaker.
5.3.16	When most of the liquid has drained from the pipette, touch the tip to the wall of the container until the flow stops and for an additional count of 10.
5.3.17	Re -weigh the beaker.
5.3.18	Calculate the weight of the water occupied by pipette and divide with density of water or theoretical as 0.99707 g/ml at 25°C.
5.3.19	Record the data in Glassware Verification/Calibration record as per Annexure No. 01.
	C.              Calibration or Verification of Burettes:
5.3.20	Fill the burette to above the zero mark and open the stopcock to fill the tip.
5.3.21	Remove air bubbles of the tip by tapping the tip while solution is draining.
5.3.22	Burette calibration is to be calibrated for 20%, 60% and 100% of the claimed volume.
5.3.23	The initial burette reading is taken 15-30 second, after the drainage of liquid has ceased.
5.3.24	The meniscus can be highlighted by holding a white piece of paper with a heavy black mark on it behind the burette.
5.3.25	Record the weight of cleaned and dried beaker at ≈ 25°C.
5.3.26	Fill the burette up to mark with boiled and cooled purified water at ≈ 25°C.
5.3.27	If burette capacity is 100  ml,then transfer 20 ml of volume of water to beaker and record the weight.
5.3.28	Repeat the same procedure after transfering 60 ml and 100 ml of water.
5.3.29	Same procedure is followed for burette of 25 ml and for 50 ml capacity .
5.3.30	Calculate the weight of the water occupied by burette and divide with density of water or theoretical as 0.99707g/ml at 25°C.
5.3.31	Record the data in Glass ware Verification/Calibration record as per Annexure.
5.3.32	For Tolerance limits of volumetric glassware refer below Annexure.
5.3.33	After calibration or verification test of the volumetric glassware it can be use for analysis and data with party COA for A grade glassware should be recorded for reference.
5.3.34	If any glassware does not passes the test of calibration, then repeat the same and reject if results are does not comply with acceptable criteria.

 

6. Definitions / Abbreviations:

• Definitions:
• Abbreviations:

 

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
TC	To Contain
g	gram
L	Litre
%	percentage

 

Tolerance Limits of Volumetric Glassware

         

• Volumetric Flasks: IS 915:2012

 

Nominal Capacity in ml	5	10	25	50	100	250	500	1000
Tolerance ± ml for Class A AAAAAA	0.025	0.025	0.04	0.06	0.1	0.15	0.25	0.4
Tolerance ± ml for Class B	0.0504	0.05	0.08	0.12	0.2	0.3	0.5	0.80

 

2    Volumetric Pipettes: IS 1117:1975

 

Nominal Capacity in ml	1	2	5	10	20	25	50	1000
Tolerance ± ml for Class A	0.007	0.01	0.015	0.02	0.03	0.03	0.05	0.08
Tolerance ± ml for Class B	0.015	0.02	0.03	0.04	0.06	0.06	0.1	0.16

 

3    Graduated Pipettes: IS 4162:1985

Nominal Capacity in ml	1	2	5	10	25
Sub division ,ml	0.01	0.02	0.05	0.10	0.2
Tolerance ± ml for Class A	0.006	0.01	0.03	0.05	0.1
Tolerance ± ml for Class B	0.01	0.02	0.05	0.1	0.2

 

• Burettes: IS 1997:1967

Nominal Capacity in ml	10	25	50	100
Sub division ,ml	0.05	0.05	0.1	0.2
Tolerance ± ml for Class A	0.03	0.03	0.05	0.1
Tolerance ± ml for Class B	0.05	0.05	0.1	0.2

 

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

 

SOP Title: Rinse And Swab Sample Analysis

1. Objective:

To lay down the procedure for Rinse and swab Sample Collection of Equipments or Machines and   Analysis.

 

2. Scope:

This SOP is applicable for Rinse and Swab Sample Collection of Equipments or Machines and Analysis of previous product residue on Equipments or Machines used for manufacturing purpose.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Rinse and Swab Sample Collection of Equipments or Machines and 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:

5.1	Residual Sample Collection :
5.1.1	Quality Control chemist should prepare the necessary solvent and accessories for swab or rinse collection.
5.1.2	After receiving the intimation of swab or rinse sample analysis from concerned department, analyst/supervisor shall make entry in “Residual Sample Entry Register” as per Annexure.
5.1.3	Quality Assurance personnel shall go to the concerned Department for collection of sample.
5.1.4	If Quality Assurance personnel visually observed any visual residue or lack of cleaning during swab sampling or rinse water collection, he / she should not collect the sample up to satisfactory washing done as per SOP of washing for particular equipment or machine.
5.1.5	Purified water shall be used for washing and rinsing, if previously drug is water soluble and physical structure of Equipment/Machine is easily washable. After washing collect the rinse sample.
5.1.6	Take swab sample from difficult to clean area of Equipment/Machine and water insoluble drugs to check previous product residue after cleaning.
5.1.7	Use Ethanol as a solvent for water insoluble drug swab sample collection or any other solvent can be used as per STP.
5.1.8	Sampling Methods for Surface Residue 1.Rinsing 2.Direct Surface Sampling (Swab sampling)
5.2	Rinse Sampling:
5.2.1	An indirect sampling method is rinse sampling. A small sample of the solution collected from the last rinse cycle of the cleaning process is analysed for the compound of interest and the residual limit is back-calculated according to the volume of solution and the contact area. There are generally two assumptions inherent in this method. The first is that the target residue is efficiently extracted into the rinsing solution. The second is that all parts of the contaminated surfaces are cleaned equally. One fairly significant advantage is the ease of collecting a part of the final rinse solution drained from the equipment. Another is that it allows evaluation of residues from all parts of the surface irrespective of the difficulty of reaching them with a swab. This makes rinse sampling ideal for clean-in-place (CIP) systems sealed systems or large-scale equipment that is difficult to disassemble. During cleaning validation program, rinse sample can be directly analysed by above methods and there is no need to develop specific preparation for rinse sample. Depending upon the concentration and number of washing, final rinse sample can be analysed and based on results residue can be calculated.
5.2.2	Production person shall wash the instrument as per defined in respective SOP
5.2.3	After Receiving Rinse sample/ Swab sample, Assign Analytical Reference Number (A. R. No.) as “RS/YY/NNN” Where, ‘RS’ stands for ‘Residual Sample’ ‘YY’ stands for ‘Last two digits of the current year’. ‘NNN’ stands for ‘Serial number i.e. 001, 002 and so on’.
	Rinse Sample Analysis:
5.2.4	Proceed for analysis as per STP/GTP for Rinse/Swab analysis of respective drug.
5.2.5	Enter all the details in Residual Sample Data Sheet.
5.2.6	Test Preparation: – Take direct reading of rinse sample given from manufacturing for Analysis. If required dilute it with diluent.
5.2.7	Blank Preparation: – Use cleaning solvent / diluent as Blank solution. (Refer STP/GTP)
5.2.8	Standard Preparation (10ppm): – Prepare 10ppm concentration standard solution by weighing accurately and diluting with suitable diluent. (Refer STP/GTP)
5.3	Swab sampling:
5.3.1	Direct surface sampling can be carried out in a number of ways, but the most common and widely accepted is swabbing. This involves wiping a predetermined area of the equipment with a swab that has been moistened with a solvent determined by the contaminating compound. Usually the surface is wiped with one side of the swab using a certain number of strokes, then the swap is flipped and the surface is wiped at 90° to the first series of stokes as shown in the following figures in refer point no. 5.3.5. Swab technique The recommended strategy is to thoroughly wet the swab head in the solvent and then squeeze the excess solvent from the swab head using the side of the solvent container. It is important to ensure that both sides of the swab are squeezed out.
5.3.2	Amongst the advantages of the swabbing method is the fact that insoluble or slightly soluble residues on the surface are more readily removed by physical “rubbing” than is the case in (for example) rinsing. It also permits direct sampling from accessible, ·         Insoluble n dried residues may be removed by physical action ·         When accessible hardest to clean area can be sampled, indicating a likely maximum level of the residue Swab selection is important in swabbing method. Swab sampling is technique dependant
5.3.3	Mark a 2 x 2 inch or 5 x 5 cm area on critical surface of the Equipment or Machine for Swab Sample Collection.
5.3.4	Quality Assurance personnel should collect the swab with cotton bud  or swab stick previously moisten with suitable solvent as per below figure:
5.3.5	Swab Sampling: this is a method for sampling from the surface by a small stick having cotton wrapped on one or both end. Following steps shall be taken for swab sampling: 1.      Pick the swab and dampen it with diluents. 2.      Put the swab template on the specified surface of the equipment. 3.      Swabbing shall be done using about 10 strokes as shown in below diagram.             Sideways                Downward             Diagonal                 Diagonal Left to Right            Right to Left   Snap swab head at the notch along edge of swab stick and allow the swab head to fall into Test Tube/vial.
	Swab Sample Analysis:
5.3.6	Test Preparation: – Take 1 Swab (given from manufacturing for Analysis) in a test tube, add 10ml of diluent and sonicate for 5minutes.
5.3.7	Blank Preparation: – Take 1 Swab (intact/pure swab stick) in a test tube, add 10ml of diluent and sonicate for 5minutes.
5.3.8	Standard Preparation (10ppm): – Prepare 10ppm concentration standard solution by weighing accurately and diluting with suitable diluent. (Refer STP/GTP)
5.3.9	Proceed for analysis as per STP/GTP for Rinse/Swab analysis of respective drug.
5.3.10	Enter all the details in Swab Sample Data Sheet.
5.3.11	If result observed out of limit analyst should intimate to Quality Assurance Department for investigation or re-cleaning of the Equipment/Machine.
5.3.12	If result observed under limit analyst should prepare a release report of swab analysis or rinse analysis with remark and data should be filed in proper manner.
5.3.13	After the analysis, analyst should hand over the Rinse/Swab Sample Data Sheet to Supervisor/Reviewer analyst for data checking.
5.3.14	Quality Control Head shall verify and approve the Residual Sample Data Sheet.
5.3.15	Production or concerned Department can receive the photocopy of Residual Sample Data Sheet for their reference (If required).
5.3.16	Methods Used for Analysis of Rinse/Swab :- 1)      Specific Test Methods  2) Non-Specific Test Methods Refer below Table;
	Specific Test Methods Non-Specific Test Methods ·      UV/Visible Spectrophotometry ·      Near Infrared Spectrophotometry (NIR) ·      High Performance Liquid Chromatography (HPLC) ·     pH ·     Titration ·     Conductivity ·     Gravimetric
5.4	Acceptance criteria
5.4.1	a.       NMT 10 ppm of any product will appear in another/ next product. b.      NMT 0.1 % of the normal therapeutic dose of any product will appear in maximum daily dose of the sub sequent product. c.       For certain allergic ingredient, penicillin cephalosporin of steroid and cytotoxic, the limit should be below the limit of detection.
5.4.2	The limit for the microbiological bioburden criteria for product contact surface should NMT 100 cfu / swab.
5.5	Calculation
5.5.1	10-ppm criteria: Maximum 10 ppm level residual contamination of the previous active pharmaceutical ingredient in the product is widely accepted in the pharmaceutical industry. Hypothetical worst case product identification of Maximum Allowable Carryover (MAC/swab) as per 10-ppm criteria in Nestor Pharmaceuticals Limited is derived as per following formula:     MAC = = R  X S X U X F = ______mg/swab   T Where, R  : 10 mg active ingredient of product A in one kg of product B S : Smallest batch size (For e.g. 5.0 kg batch size is selected hypothetically for worst MAC calculation). T  : Total Surface area of equipment’s F  : Recovery factory (Recommended 0.75).                          U = Swab area i.e. 4X4 sq. inch For e.g. 10 X 5.0 X 4 X 4  X 0.75 53000 = 0.0113mg/swab =  0.0113 mg/swab X 1000 = 11.3 mcg/swab
	Calculation for MAC (maximum allowable carryover ):- Therapeutic dose based criteria:-
5.5.2	1/1000th of smallest recommended daily dose Criteria: Maximum Allowable Carryover (MAC) of previous product in the subsequent product is calculated as: MAC =  SRDD X SF X SBS X U X 1000 X 1000 X F = ____mg/swab   LRDD X TSAR             Where, SRDD = Smallest Recommended Daily Dose of product among the all products in mg. SBS    = Smallest Batch Size in kg. SF= 1/1000, safety factor U = Swab area i.e. 4X4 sq. inch LRDD = Largest Recommended Daily Dose of product among the all products in mg. TSAR = Total Surface area of equipment’s in sq. inch F: Recovery factory (Recommended 0.75).
5.5.3	Swab recovery test shall be a part of the method validation to estimate the recovery during swabbing.
5.5.4	The recovery shall be accounted for calculation of the cumulative retention of residue.
5.5.5	Safety Factor Term:- Options to apply safety factors uniformly within a plant –          For Topical product: 10 to 100* –          For Oral Dosage Product: 100 to 1000* –          For Parental/ Ophthalmic product: 1000 to 10000 –          For Research investigational product: 10000 to 100000 –          *Note Significant rationale must be given if safety factor is less than the industry-standard 1000
	Clean Hold Time (CHT) and Dirty Hold time (DHT):-
5.5.6	Clean hold Time: –          Following Cleaning, how long equipment remains ‘clean’ before reuse. –          Not concerned with the process residue: focus is on controlled storage( bioburden proliferation ) Dirty Hold time: –          How long ‘dirty’ equipment can remain dirty prior to cleaning. –          Generally, longer DHT → increasingly difficult to clean

 

6. Definitions / Abbreviations :

• Definitions :
• Cleaning: Removal of Residue and Contaminants to be a Controlled level. The residue and contaminates Can be by cross contamination from previously manufactured products equipment or from the procedure( detergent/sanitizers) or degradation product resulting   from the cleaning process itself, as well as microorganism*.
• Cleaning verification: A quality control process for determining the effectiveness of a cleaning process for a specific cleaning event or to release of equipment for use.
• Cleaning Validation: A methodology used to assure effectiveness and consistency of cleaning process to remove residue and contaminates.
• Type A Cleaning: It is dry cleaning process performed between the same type of products or   campaign batches generally called as batch to batch changeover. This type of cleaning   consists of removal of drug powders from the surface with the help of clean cloth or     scraper/scrubber.

 

• Type B Cleaning: It is wet cleaning process in which cleaning solution is used for cleaning. This is performed in following cases:
• MACO: Maximum allowable carryover is the upper limit of residue that can be allowed after cleaning process. Cleaning procedure should be efficient to remove the residue below the MACO value.
• Rinse Sampling: this is the method by which all the contact surface of the cleaned equipment is rinsed with specified amount of water then collecting certain volume of the rinse water into a vial.
• Cleaning Hold Time: Cleaning hold timeis considered to be the time between the completion of cleaning and the initiation of the subsequent manufacturing operation. Dirty hold time is the time between the end of manufacturing and the beginning of the cleaning process.
• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
STP	Standard Testing Procedure
GTP	General Testing Procedure
QA	Quality Assurance
UV	Ultra Violet
No.	Number
NMT	Not more than
cm	centimeter
ppm	parts per million

 

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

 

 

 

 

 

 

 

SOP Title: Preventive Maintenance of Instruments/Equipment’s

1. Objective:

To lay down the procedure for Preventive Maintenance of Instruments/Equipment’s.

2. Scope:

This SOP is applicable for Preventive Maintenance of Instruments/Equipments to prevent the failure of Instruments/Equipments before it actually occurs in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Preventive Maintenance of Instruments/Equipments in Quality Control Department as per this SOP.
• Engineering Department: To carry out preventive maintenance as per schedule and procedure defined.
• 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	Preventive Maintenance of Instruments/Equipment’s:
5.1.1	Preventive Maintenance is a schedule of planned maintenance actions aimed at the prevention of breakdowns and failures.
5.1.2	The ideal Preventive Maintenance programme would prevent all equipment failures before it occurs.
5.1.3	Long Term Benefits of Preventive Maintenance: 1. Improved Instrument Reliability 2. Decreased cost of replacement 3. Reduces Equipments/Instruments Downtime
5.1.4	Preventive Maintenance activities include Equipments/Instruments checks, partial or complete overall checks at specified interval/period, e.g. oil changes, lubrication of parts, cleaning of parts.
5.1.5	In addition to the above the analyst has to maintain the usage log book for all the major instruments.
5.1.6	On the basis of the usage record and observations, an idea of the replacement of worn parts can be obtained.
5.1.7	Preventive Maintenance of all major equipments is to be carried out as per Annual Preventive Maintenance Schedule by Engineering Department and the necessary records of the same should be maintained.
5.1.8	On the day of Preventive Maintenance, label the Instrument/Equipment as “Under Preventive Maintenance”.
5.1.9	Carry out the parameters for Preventive Maintenance as mentioned in individual Instrument/Equipment SOP.
5.1.10	Preventive Maintenance Checklist shall be prepared for all Instruments/Equipments as per Annexure.
5.1.11	Preventive Maintenance shall be carried out for analytical Instruments/Equipments as per frequency mentioned in Annual Preventive Maintenance Schedule and Preventive Maintenance window shall be ± 7 working days from the due date of PM.

 

6. Definitions / Abbreviations:

• Definitions:
• Breakdown: Any activity leading to operation of Instrument/Equipment other than the set parameters or unusual sound or vibration observed in the instrument/equipment.
• Preventive Maintenance: Maintenance activity performed to ensure that the Instrument/Equipment will function smoothly and to avoid breakdowns. These activities are performed as per predefined frequency.

 Abbreviations:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
No.	Number
PM	Preventive Maintenance

  

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

 

SOP Title: Handling of Instruments/Equipments Breakdown

1. Objective:

To lay down the procedure for Handling of Instruments/Equipments Breakdown.

2. Scope:

This SOP is applicable for Procurement and Handling of Instruments/Equipments Breakdown in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Handling of Instruments/Equipments Breakdown 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	Handling of Instruments/Equipment’s Breakdown:
5.1.1	Equipments/Instruments that has been subjected to overloading or mishandling which gives improper results or has been shown to be defective or out of calibration shall be kept out of routine use.

 

5.1.2	When Instrument/Equipment fails to qualify the test for calibration or validation, Quality Control Analyst should be report to the Supervisor and affix the label as “Under Maintenance”.
5.1.3	Whenever a breakdown occurs, a complaint note in complaint format shall be sent to the HOD (Engineering) by Supervisor/HOD.
5.1.4	If major fault observed in Equipments/Instruments, Supervisor should be consult to HOD of QC and further HOD of Engineering Department.
5.1.5	When Engineering Department rectify the problem, the Equipments/ Instruments should be recalibrated or validated for performance.
5.1.6	If the Engineering Department declares the critical fault and requirement for outside engineer or parts, than put the label as “Non-Functional Equipment” till the problem is rectified.
5.1.7	For each and every activity performed, update the “Instrument/Equipment Usage Log Book” and “Instrument/Equipment History Card” as per SOP “Calibration of Instruments and Equipments”.
5.1.8	All repair/service documentation shall be kept with the Instrument/ Equipment history card in order to provide a concise history for each instrument.

 

5.1.9	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.
5.1.10	If any spare or part procured for this Equipments/Instruments, it should be recorded with detailed in Instrument/Equipment History Card.
5.1.11	When Equipments/Instruments ready for use after repairing, it is compulsory to check calibration parameter or validation for performance check or operational qualification tests based on assessment.
5.1.12	After successful qualification of the tests, Instruments/Equipments shall be release for routin use.
5.1.13	If any Instrument/ Equipment is not possible to repair, then it shall be retired from the department with proper assessment and impact evaluation by filling change control.
5.1.14	Retired Instrument/ Equipment shall be send it back to manufacture or hand over to Engineering Department for further disposal.

 

6. Definitions / Abbreviations:

• Definitions:
• Abbreviations:

 

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
No.	Number
HOD	Head Of Department

 

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

 

SOP Title: Preparation of Analytical Work Report         

1. Objective:

To lay down the procedure for Preparation of Analytical Work Report in Quality Control Department.

2. Scope:

This SOP is applicable for Preparation of Analytical Work Report used to record results of analysis of Raw Material, Finished Product, In process Sample, Packing Material, Working Standard, Stability study in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Preparation of Preparation of Analytical Work Report 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 AWR:
5.1.1		Analytical Work Report comprises of Header, Footer and Body.
5.1.2		Prepare Analytical Work Report as per following procedure.
5.1.3		Header should contain the following:
5.1.4		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 ‘Analytical Work Report’ (Font: Times new roman, Font style: Bold, font size 14) 6.      Sub title as ‘Raw Material’ (Font: Times new roman, Font style: Bold, font size 14) 7.      ‘AWR No.’ i.e. Analytical Work Report Number (Font: Times new roman, Font style: Bold, font size 12)
5.1.5		Body contains all the detail information of Raw Material, Number of tests to be carried out with details, Results obtained and as per respective Raw Material Specification.
5.1.6		Body is divided into two parts.
5.1.7		1.         AWR No. 2.         Name 3.         A. R. No. 4.         Manufacturer 5.         Supplier 6.         Batch No. 7.         Quantity Received 8.         Analysis completion Date 9.         GRN No. and Date 10.     Mfg. Date 11.     Exp. Date 12.     Quantity Sampled 13.     Sampled by and Date 14.     Effective date 15.     Version Number 16.     Refer STP No.
5.1.8		Remaining pages of AWR includes Raw Material below the Header.
5.1.9		Second part contains all the Tests parameters as per respective Standard Test Procedure and Specification.
5.1.10		All the tests should be in the same order as per Standard Test Procedure.
5.1.11		Each test should include following details: 1. Name of the test 2.   Instrument ID No. (if applicable) 3. Details of Solution Preparation/Calculations (if applicable) 4. Reference Materials Details (if applicable) 5. Observations 6. Analysed By/Date 7. Complies/Does not comply
5.1.12		Footer comes only on the last page of AWR.
5.1.13		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 Raw Material Specification No.: _____________
5.1.14		After remark, footer contains Analysed by, Checked by and Approved by signatures with date and revision history.
5.1.15		Analyst (who performed analysis), Reviewer or supervisor (who checked the Analytical Work Report) and Quality Control Head (who approves the Analytical Work Report) should sign on the AWR.
5.2
5.2.1		Follow the same procedure as mentioned for preparation of Raw Material AWR except the following:
5.2.2		In the header, Title shall be ‘Finished Product’.
5.2.3		Body contains all the detail information of Finished Product, Number of tests to be carried out with details, Results obtained and as per respective Finished Product Specification.
5.2.4		First page of AWR includes all the detail information of Finished Product as follows: 1. AWR No. 2. Name 3. Batch No. 4. A. R. No. 5. Batch Size 6. Mfg. Date 7. Exp. Date 8. Quantity Sampled 9. Sampled by and Date 10. Analysis completion Date 11. Effective Date 12. Version Number 13. Refer STP No.
5.2.5		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 Finished Product Specification No.: _________________
5.3
5.3.1		Follow the same procedure as mentioned for preparation of Raw Material AWR except the following:
5.3.2		In the header, Title shall be ‘In process Sample’.
5.3.3		Body contains all the detail information of In process Sample, Number of tests to be carried out with details, Results obtained and as per respective In process Sample Specification.
5.3.4		First page of AWR includes all the detail information of In process Sample as follows: 1.         AWR No. 2.         Name 3.         Batch No. 4.         A. R. No. 5.         Batch Size 6.         Mfg. Date 7.         Exp. Date 8.         Quantity Sampled 9.         Sampled by and Date 10.     Analysis completion Date 11.     Effective Date 12.     Version Number 13.     Refer STP No.
5.3.5		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 In process Sample Specification No.: _________
5.4
5.4.1		Follow the same procedure as mentioned for preparation of Raw Material AWR except the following:
5.4.2		In the header, Title shall be ‘Packing Material’.
5.4.3		Body contains all the detail information of Packing Material, Number of tests to be carried out with details, Results obtained and as per respective Packing Material Specification.
5.4.4		First page of AWR includes all the detail information of Packing Material as mentioned in the Raw material AWR preparation.
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 and Packing Material Specification No.: __________
5.5		Preparation of Working Standard AWR:
5.5.1		Follow the same procedure as mentioned for preparation of Raw Material AWR except the following:
5.5.2		Follow the same procedure as mentioned for preparation of Raw Material AWR 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, Number of tests to be carried out with details, Results obtained and as per respective Working Standard Specification.
5.5.5		First page of AWR includes all the detail information of Working Standard as follows:
5.5.6		1.      AWR No. 2.      Name 3.      WS No. 4.      Source Batch No. 5.      Source A. R. No. 6.      Evaluated with Reference Standard No. 7.      Reference Standard Lot No. / Batch No. 8.      Analysis completion Date 9.      Mfg. Date 10.  Exp. Date 11.  Manufacturer 12.  Supplier 13.  Effective date 14.  Version Number 15.  Refer STP No.
5.5.7		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.
5.5.8		Follow the same procedure as mentioned for preparation of Raw Material AWR except the following:
5.6
5.6.1		Follow the same procedure as mentioned for preparation of Raw Material AWR except the following:
5.6.2		In the header, Title shall be ‘Stability Study’.
5.6.3		Body contains all the detail information of Stability Sample, Number of tests to be carried out with details, Results obtained as per respective Stability Study Specification.
5.6.4		First page of AWR includes all the detail information of Stability Sample as follows:
5.6.5		1.    AWR No. 2.    Name 3.    Batch No. 4.   Batch Size 5.   Mfg. Date 6.   Exp. Date 7.   A. R. No. 8.Storage Conditions 9.     Stability Period 10.               Quantity Sampled 11.               Sampled by and Date 12.               Effective Date 13.               Version Number 14.               Analysis completion Date 15.               Refer STP No.
5.6.6		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/IHS and Stability Study Specification No.: __________
5.7
5.7.1		Follow the same procedure as mentioned for preparation of Raw Material AWR except the following:
5.7.2		In the header, Title shall be ‘Purified Water/ Raw Water/Treated Water/Soft Water/Water Validation’.
5.7.3		Body contains all the detail information of Water Sample, Number of tests to be carried out with details, Results obtained and as per respective Water Specification.
5.7.4		First page of AWR includes all the detail information of Water Sample as follows:
5.7.5		1.    AWR No. 2.    Name 3.    Quantity Sampled 4.    A. R. No. 5.    Sampling Point 6.    Sampled by and Date 7.    Date of Analysis 8.    Effective Date 9.    Version Number 10.   Refer STP No.
5.7.6		Footer contains final conclusion of the analysis as follows: Remark: The water sample complies / does not comply with respect to the above tests as per IP/BP/USP/IHS and water Sample Specification No.: _________
5.7.7		Numbering system for Analytical Work Report: AWR/XXX Where     AWR:  Analytical Work Report XXX :  Serial number of the Analytical Work Report
5.7.8		AWR also shall include Version No. which begins with 00 and continue 01, 02……during revision.
5.7.9		All Analytical Work Report should contain AWR No.

 

6. Definition / Abbreviations :

• Definition:
• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
No.	Number
AWR	Analytical Work Report
A. R. No.	Analytical Reference Number
IP	Indian Pharmacopoeia
BP	British Pharmacopoeia
USP	United State Pharmacopoeia
Mfg.	Manufacturing
Exp.	Expiry
STP	Standard Testing Procedure

 

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

SOP Title: Poisonous Chemicals

1. Objective:

To lay down the procedure for Handling of Poisonous Chemicals used in Quality Control Department.

2. Scope:

This procedure is applicable for control, careful handling and issue of Poisonous Chemicals used in the Quality Control Department.

3. Responsibility:
   • Quality Control Department: To prepare and review the SOP. To follow the procedure for control and careful handling and issue of Poisonous Chemicals 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:
5.1.1	Use personal protective equipment such as hand gloves, nose masks, goggles while working with hazardous, corrosive, flammable, toxic chemicals.
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 store or expose the chemicals near the flame or excessive heat.
5.1.4	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	Procedure for Handling of Poisonous Chemicals:
5.2.1	For receipt of Poisonous Chemicals refer SOP ‘Receipt, Storage and Handling of Chemicals in Laboratory’.
5.2.2	Enter the details of the Poisonous Chemicals received in “Chemical Receipt Register” and affix receipt label as per SOP.
5.2.3	Refer Annexure for list of Poisonous Chemicals.
5.2.4	Maintain the “Poisonous Chemical Stock and Consumption Record” as per define Annexure.
5.2.5	Preparation procedure shall be carried out in a well-ventilation fuming hood.
5.2.6	Store Poisonous Chemicals in separate cupboard with lock and key under supervisor control.
5.2.7	The key should be with Supervisor /Head of Department.
5.2.8	Affix dangerous mark sticker indicating they are poisonous chemicals.
5.2.9	Whenever any new Poisonous Chemical is taken from the stock for use, analyst should enter the date of opening on receipt label and entry should be made on “Poisonous Chemical Stock and Consumption Record” as per Annexure.
5.2.10	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.
5.2.11	In-case of inhalation of Poisonous Chemicals, give Antidotes as per define Annexure.
5.2.12	If the expiry date of Poisonous Chemicals/Solvents is not defined by the manufacturer then all the Poisonous Chemicals/Solvents should be used within three years after the date of opening.
5.2.13	Example: If the analyst opens Arsenic bottle on 25/06/24, then the date of opening shall be 25/06/24 and the validity shall be 24/06/27.
5.2.14	If the expiry date of Poisonous 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.
5.2.15	Example: If Formaldehyde bottle has expiry date as 05/2024 and the analyst opens Formaldehyde bottle on 18/06/22, then the date of opening shall be 18/06/22 and the validity shall be 31/05/24.
5.2.16	Consider the last date of expiry month to assign validity.
5.2.17	Intact poisonous chemicals/solvents should be used within five years from the date of manufacturing.
5.2.18	If the date of manufacturing is not available then intact poisonous chemicals/solvents should be used within five years from the date of receipt.
5.2.19	If any poisonous chemicals/solvents shows deterioration e.g. sedimentation, precipitation, crystallisation, discoloration, change in physical appearance shall be discarded regardless of validity.
5.2.20	For destruction of any Poisonous Chemicals/Solvents, refer SOP “Destruction of Laboratory Waste”.

 Definitions / Abbreviations:

• Definitions:
• Abbreviations:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
MSDS	Material Safety Data Sheet

 

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