In Process Quality Assurance (IPQA) SOP

By / Quality Assurance / QA, SOP /

IPQA SOP | SOP for In process quality assurance in pharmaceutical industry |

  • IPQA SOP covers below points:
    • IPQA roles and responsibilities
    • IPQA Checklist for Raw Material 
    • IPQA Checklist for Granulation / Blending Stage
    • IPQA Checklist for Compression Stage
    • IPQA Checklist for Coating Stage
    • IPQA Checklist for Capsule
    • IPQA Checklist for Over Printing Details
    • IPQA Checklist for Packing Material
    • IPQA Checklist for Primary and Secondary Packing
    • IPQA Checklist for Strip / Blister Packaging
    • IPQA Checklist for Finished Goods Warehouse
1.0 OBJECTIVE :
  • The purpose of this SOP is to provide a detailed procedure to IPQA personnel while performing IPQA checks during manufacturing and packing of product.
2.0 SCOPE :
  • This procedure is applicable to dispensing area and all Production departments.
3.0 RESPONSIBILITY :
  • IPQA chemist and above
4.0 ACCOUNTABILITY:
  • Q.A. Head
5.0 PROCEDURE :

5.1 Ensure that the personal hygiene of employee’s is maintained as per SOP for Personal Hygiene

5.2 Ensure the proper gowning as per SOP.

5.3 Safety appliances like nose mask and hand gloves are necessary to use during IPQA round.

5.4 Check out daily balances calibration activity in presence of IPQA personnel.  

5.5 Ensure the Instruments / machines are duly calibrated, if calibration date is due, calibrate the instrument / machine as per respective procedure before taking it for operation.

5.6 Use necessary safety appliances like nose mask, gloves and safety goggles etc. during in-process round.

5.7 Do not start any activity without getting approval (Line clearance) from QA personnel.

5.8 Destroy all In-process material, non- recoverable rejects, excess overprinted packing material and rubber stereos after packing is carried out in presence of IPQA personnel.

5.9 Ensure that every stage of process, appropriate status label is affixed on equipment / machines and containers.

5.10 Maintain the cleanliness and orderliness in the departments.

5.11 Report non compliance immediately to QA Head and prepare the deviation and investigate the failure cause as per SOP for Failure investigation.

5.12 Ensure that all raw materials are dispensed under RLAF. 

5.13 Ensure that documents are complete after completion of every process stage in time.

5.14 Verify that yield reconciliation is being done and found correct at the end of each operation.

5.15 IPQA Checklist for Raw Material :

  • Ensure that the “Under Test” material is stored in quarantine area.
  • Ensure that the transfer of approved material in the appropriate racks for traceability.
  • Ensure the storage conditions of raw materials are met. 
  • RM label (Manufacturer’s Label) & QC label match for details.
  • Ensure the following points on labels –
    • Name of material with presence and correctness of Pharmacopoeial standard. 
    • B. No.,
    • Quantity,
    • GRN No. ,
    • Mfg. date,
    • Expiry date
    • Name of manufactures etc.
  • Ensure Analytical Report No. is legible and should match with the computer record.
  • Check Re-testing date.
  • Ensure that the loose containers are securely tight and not open (after issuing of material).
  • Ensure there is only one loose container of one material.
  • Ensure that the loose container is as per FIFO / FEFO order.
  • Ensure that the pressure differential, temperature & relative humidity record in the respective area is maintained.
  • Ensure that the details of dispensed material label are matching with container label and requisition.
  • Re-check the dispensed material after receipt of material by production chemist for weight and label.
  • Ensure balances & floors are cleaned as per respective procedures after Dispensing.
  • Ensure from the stock documents material is issued by first in first out/ first expiry first out system.
  • Check the physical stock of raw materials randomly and prepare the report. If any discrepancy is observed report to Head Warehouse and Head QA for further action.

5.16 IPQA Checklist for Granulation / Blending Stage:

  • Check and ensure that machine Equipment/ Accessories bears the machine / container status label of current batch.
  • Verify all the entries are completed in Batch manufacturing Record up to the previous stage of that activity.
  • Ensure the temperature, humidity and pressure differential in Granulation / Blending area is within limit and record the observations in BMR & BPR.
  • Withdraw sample after completion of process as per BMR and submit the withdrawn sample to Quality Control Department for analysis.

5.17 IPQA Checklist for Compression Stage:

  • Verify all the entries are completed in Batch manufacturing Record up to the previous stage of that activity.
  • Ensure that blend is analyzed and Approved by Quality Control Department. Affix the approved label before start up of the compression.
  • On intimation of change over, IPQA personnel shall follow the SOP for line clearance.
  • Ensure that proper status labels are affixed in time.
  • Randomly take the tablets during compression and check the following parameters and record the observations in IPQA reports, i. e., DT, Appearance, Friability, Uniformity of weight, Hardness, Thickness.
  • Check both side samples (L.H.S. and R.H.S.) respectively
  • Take tablets from L.H.S. and R.H.S. respectively from the compression machine when machine is on and tablets are getting compressed.
  • Collect Tablets in a clean and dry polythene bag, close the bag and take it to the IPQA room for IPQA check.
  • Check visually for absence of any defect, i.e., capping, sticking, mottling, lamination, chipping, picking etc.
  • Before commencing weighing of the Tablets put fresh clean and dry butter paper inside the weighing bowl.
  • Take 20 tablets from L.H.S. & R.H.S. for weight of 20 Tablets and Uniformity of weight test.
  • First weigh 20 Tablets together record the weight and then from same Tablets weigh one by one tablet for Uniformity of weight test. Note down the weights on IPQA report.
  • Take 5 tablets and check thickness and diameter.
  • Take 5 tablets and check hardness.
  • Take 6 tablets at random from compression machine and check disintegration time.
  • Take 10 / 20 tablets at random from compression machine and check friability as per the respective product Master Formula Record.
  • If any of the above tests fails, to the specification, inform to production officer for corrective action and then segregate tablets compressed during that specific period. (i. e., the period from earlier checking and till it failed). Remove the tablets from the containers, check twice, if it does not comply with test then quarantine the containers and follow the deviation procedure with proper authorization.
  • Prepare the deviation reports with action and get the approval from QA Head and take the corrective action and attach to BMR.
  • Collect rejected tablets during IPQA test like broken, damaged and/or out of limit Tablets in a separate container for destruction with proper label of Rejected Tablets on the container. Keep the container always closed and at the end of shift destroy these Tablets.
  • During IPQA test if any of the test / machine giving fail results, inform immediately to Production Head and QA Head for appropriate action.
  • Withdraw sample after completion of process as per BMR and submit the withdrawn sample to Quality Control Department for analysis.

5.18 IPQA Checklist for Dissolution test for pre compressed tablets:

  • Compress few tablets and send the sample to QC for testing of dissolution test as a sample of pre-compressed tablets.
  • If the product of new molecule will be manufactured, the sample of pre-compressed tablets will be tested for dissolution test.
  • If the result of dissolution test found satisfactory, further compression will be started.
  • If the result of dissolution test found unsatisfactory, inform to production. Further re-processing or other required CAPA will be taken and sample will be sent to QC for analysis.
  • The analytical data of dissolution test will be stored along with in process data of compressed tablets in QC department.

5.19 IPQA Checklist for Coating Stage:

  • Verify all the entries are completed in Batch Manufacturing Record up to the previous stage of that activity.
  • Ensure that compressed tablets are analyzed and Approved by Quality Control Department. Affix the approved label before start up of the coating.
  • On intimation of change over, follow the SOP for line clearance.
  • Ensure that proper status labels are affixed in time.
  • Ensure the temperature, humidity and pressure differential in coating are within limit and record the observations in BMR.
  • Verify that yield reconciliation is being done and found correct at the end of each operation.
  • Take 20 tablets per lot from coating pan after completion of coating process of respective lot.
  • Collect Tablets in a clean and dry polythene bag, close the bag and take it to the IPQA room for IPQA check.
  • Check visually for absence of any defect, i.e., uniformity of colour, side edge broken, Mottling, Peel off etc.
  • Check the parameters and note the observations in IPQA reports, i.e., Appearance, Uniformity of weight and Disintegration Test etc.
  • Before commencing weighing of the Tablets put fresh clean and dry butter paper inside the weighing bowl.
  • Take 20 tablets from coating pan for weight of 20 Tablets and Uniformity of weight test.
  • First weigh 20 Tablets together record the weight and then from same Tablets weigh one by one tablet for Uniformity of weight test. Note down the weights on IPQA report.
  • Take 6 tablets at random from coating pan and check disintegration time.
  • If any of the above tests fails, to the specification, inform to production head for corrective action and then segregate coating tablets during that specific period. (i. e. the period from earlier checking and till it failed). Remove the tablets from the containers check twice, if it does not comply with test then quarantine the containers and follow the deviation procedure with proper authorization.
  • Withdraw sample after completion of process as per BMR and submit the withdrawn sample to quality control for analysis.

5.20 IPQA Checklist for Capsule :

  • Randomly check the manufacturing process at the different stages as per BMR.
  • On intimation of change over, IPQA officer shall follow the SOP for line clearance.
  • Ensure that proper status labels are affixed in time.
  • Ensure the temperature, humidity and pressure differential in capsule filling / tablet compression, Inspection and Packing area are within limit and record the observations in BMR & BPR.
  • Check the on line Encapsulation at the start of the batch and after each break.
  • Verify that yield reconciliation is being done and found correct at the end of each operation.
  • Randomly take approximately 20 capsules respectively from the capsule filling machine.
  • Collect capsules in a clean and dry polythene bag, close the bag and take it to the IPQA room for IPQA check.
  • Check visually for absence of any defect, i.e., denting, pinhole, polishing, etc. in capsule.
  • Check the parameters and note the observations in IPQA reports, i.e., Appearance, Uniformity of weight, Disintegration Time, locking length, etc.
  • Before commencing weighing of the Capsules put fresh, clean and dry butter paper inside the bowl of weighing balance.
  • Take 20 Capsules for Uniformity of weight test.
  • First weigh 20 Capsules together and record the weight and then from same Capsules weigh one by one capsule for Uniformity of weight test. Note down the weights in IPQA report.
  • To avoid product to product cross contamination, whenever a product for weighing is changed, every time use a fresh butter paper for weighing the Capsules.
  • Once Uniformity of test is over by using 20 Capsules, from same capsules perform Disintegration test and check locking length.
  • Use 6 Capsules from above 20 Capsules for Disintegration test.
  • Use 5 capsules and measure their locking length by Calibrated Vernier caliper.
  • If any of the above tests fails, to the specification, inform to production head for corrective action and then segregate capsules during that specific period. (i. e. the period from earlier checking and till it failed). Remove the capsules from the containers check twice, if it does not comply with test then quarantine the containers and follow the deviation procedure with proper authorization.
  • Prepare the deviation reports with action and get the approval from QA Head and take the corrective action and attach to BMR.
  • Collect rejected capsules during IPQA test like damaged and/or out of weight limit/specifications in a separate container for destruction with proper label of Rejected capsules on the container. Keep the container always closed and at the end of shift destroy these capsules.
  • During IPQA test if at any time found that capsules are going out of limit/specifications during capsule filling, immediately inform it to the production Head and QA Head for appropriate action.

5.21 IPQA Checklist for Over Printing Details:

  • Ensure that Batch no, Mfg. date, Exp. date, Retail price, Mfg. Lic. No., Neutral Code etc, is correct and readable on carton/ catch cover.
  • The over printing shall be checked by QA person at the initial, middle and final stage of overprinting and the record shall be recorded in the BPR.
  • For strips / Blisters Mfg. date, Expiry date, Retail price, Batch no. etc, correct and readable.
  • Printing matter on strips / Blisters, carton & catch cover.
  • Presence of specified no. of Tablets / Capsules in each Strips / Blisters.
  • Absence of any defects like broken tablets, Empty pocket, pinholes, damaged Capsules etc.
  • Check content of units for all relevant items like insert. etc.
  • If any above defect found, then inform to production officer for corrective action and get the boxes rechecked, if required.
  • Remove the samples for analysis and control sample in random.
  • Replace the units from last / loose case in presence of production chemist / Packing Supervisor, and then repack the box with proper initials.
  • After removing the complete quantity of sample for Analysis and control sample, enter the quantity in respective BMR, BPR and forward the analysis samples to the Sample room and control samples in control sample room of Quality Control Department.
  • In-process tests for critical processes shall be performed by Production and Quality Assurance dept. separately.
  • These tests shall be carried out in accordance with the general test procedure specified and limits as per the product specification given in concerned product / batch Packing record.

5.22 IPQA Checklist for Packing Material :

  • Ensure the proper segregation of materials as per Analytical Report Number wise & product wise.
  • Material with special instruction are kept separately or taken necessary care.
  • Ensure proper disposal of the rejected items.
  • Ensure material issuing first in first out.

5.23 IPQA Checklist for Primary Packing Area:

  • Verify Batch Packing Record is completed and submit to Q.A. department.
  • Ensure that semi finished is analyzed and released by Quality Control Department. Affix the approved label before start up of the primary packing.
  • On intimation of change over, IPQA personnel shall follow the SOP for line clearance.
  • Ensure the temperature, humidity and pressure differential in primary packing within limit and record the observations in BPR.
  • Verify that yield reconciliation is being done and found correct at the end of each operation.

5.24 In case tablets are to be packed in Bottle / Jar:

  • Check the details of packing operation indicated on display board, adjacent to the packaging line with the batch details mentioned in BPR.
  • Ensure that the packing material on the line is as per bill of packaging materials.
  • Verify that the overprinting details on the specimen of Label, is attached after approval with BPR.

5.25 IPQA Checklist for Strip / Blister Packaging:

  • Ensure the overprinting batch details of the strips and cartons that they match with the details given in the BPR.
  • Randomly check the final packs for correct details as given below –
    • Name of the Product  
    • Quantity
    • Batch no.
    • Mfg. and Exp. date
    • Code no. and other details if any.
    • Check embossing/Printing on strip & blister.
    • Sealing of strip/blister’s corners and cutting.
    • Visual defect in strips/blisters like cut pockets, missing tablet in strip / blisters and smudging of overprinting on carton / strips / blister etc.
    • To ensure that set the temperature of both sealing forming roller is maintained during blister packing and observation of the temperature are recorded by operator in BPR in respective table.
    • Remove strips / blisters from machine for leakage test and check leakage as per procedure. Limit is 0 leakages. If leakages observe 1 or more pocket, inform to operator for adjustment & again take leak test after 10 mins of adjustment. If more than 2 pockets shows leakages, “Hold” & remove tablets / capsules & again pack it. Note down the temperature of roller.
    • Withdraw control sample, stability sample and testing sample of strip/blister packing from the running line and submit to quality control department for analysis.

5.26 IPQA Checklist for Secondary Packing:

  • Open the box by removing Biaxial Oriented Polypropylene tape and check physical quantity of inner shipper, cartons as per specifications.
  • Check one inner shipper and final pack for correct details as given below.
  • After completion of packing operation ensure that the extra packing materials are returned to warehouse department and record is maintained.
  • If any above defect found, then inform to production officer for corrective action and get the boxes rechecked if required.
  • Remove the samples for analysis and control sample in random.
  • Replace the units from last/loose case in presence of production chemist / Packing Supervisor, and then repack the box with proper initials.
  • After removing the complete quantity of sample for Analysis and control sample. Enter the quantity in respective BMR, BPR and forward the analysis samples to the Sample room and control samples in control sample room of Quality Control Department.
  • In-process tests for critical processes shall be performed by Production and Quality Assurance dept. separately.
  • These tests shall be carried out in accordance with the general test procedure specified and limits as per the product specification given in concerned product/ batch manufacturing record.

5.27 IPQA Checklist for Finished Goods Warehouse:

  • Ensure the dispatches of the product are done only after approval.
  • Check randomly physical stock is matching with stock statement.
  • Ensure the proper storage of export goods.
  • Ensure strapping is carried out as required.
  • Prepare the inspection report in duplicate in case of export consignment.
  • If any discrepancy is observed, inform to concerned officer for corrective action and one copy of the report send to Warehouse officer and one copy preserved for QA record.
 6.0 ABBREVIATIONS:
AbbreviationExpanded form
SOPStandard Operating Procedure
Q.A.Quality Assurance
Q.C.Quality Control
BMRBatch Manufacturing Record
BPRBatch Packing Record
no.Number
Mfg.Manufacturing
Exp.Expiry
IPQAIn Process Quality Assurance
L.H.S.Left Hand Side
R.H.S.Right Hand Side

7.0 ANNEXURES:

Nil

8.0 SOP REFERENCES
  • In-House

END OF THE SOP