SOP on In-process checks during Dry powder injection manufacturing & packing.
Objective: To lay down a procedure for in process checks during Dry powder injection manufacturing & packing.
Scope: This procedure is applicable to formulation unit.
Responsibility: IPQA Officer/Executive shall be responsible for preparation & execution of the SOP.
Accountability : Head QA shall be accountable for compliance of the SOP.
Procedure : In process checks shall cover the processes like bung washing/ processing, vial washing, sterilization cycle, vial filling & bunging, labeling & packing.
IPQA shall carry out the routine checking & testing of the batches manufactured.
IPQA checks shall include in process tests during vial washing, bung washing, bung sterilization, sterilization of machine parts and accessories, vial sealing, vial inspection & packing.
IPQA shall perform in process checks ,For validation batch and exhibit batch in process checks shall be performed as per sampling plan and test batch monitoring plan respectively.
Vial washing:
Purified water to be used shall be approved by QC before starting the operation.
WFI to be used in the operation shall be approved by QC before starting the activity.
Line clearance of area & equipment shall be given as per “SOP on line clearance”.
Purified water, WFI & Compressed air shall be checked as per BMR before starting the operation.
Initially washed vials shall be as per requirement collected and checked for particulate matter. Once the result complies with the BMR, operation shall be started.
During operation 5 vials shall be collected every 4 hrs. & checked for particulate matter & recorded in BMR.
Sterilization Process
WFI to be used in the operation shall be approved by QC before starting the activity.
Line clearance of area & equipment shall be given as per “SOP on line clearance”.
Vacuum leak test shall be done before starting the day’s activity.
Before sterilizing powder filling machine parts rinse sample shall be collected from each part & checked for visible, sub-visible particles & bacterial endotoxin test. It should be recorded in BMR. Sterilization operation may be continued further but batch filling shall be started only after getting released from QC.
Water sample of after completing rubber bung washing cycle-II shall be checked by IPQA for particulate matter before starting sterilization cycle & recorded in BMR.
Vial filling, Bunging, sealing and optical inspection
Line clearance of filling & bunging area shall be given as per “SOP on line clearance”.
On completion of initial setting, filled vials shall be checked for in process parameters.
After unloading every API container IPQA person shall check required vials for visible & sub-visible particulate matters for API from each container used during the filling and attach the reports with BMR.
Performed in process checks of the filled vials after initial set up, allow further operation when all the parameters are with in specified limits given in BMR.
Sealed Vials shall be checked for sealing efficiency test, leak test initially by taking 7 vials, thereafter every 2 hours & shall be recorded in BMR.
Check 5 sealed vials for reconstitution initially and every 4 hrs. and record in the BMR.
Furthermore, check 20 optically tested vials for defects like glass vial, sealing, foreign particle & filled volume defects initially and every 2 hrs.
Labeling and packing
Line clearance of labeling & packing area shall be given as per “SOP on line clearance”.
Before start the operation, IPQA person shall verify & approve for packing material as per BPR.
After the coded label checked by production , IPQA shall verify and approve the coding details on the label & packing material for details like Batch Number, MFG. date, EXP. date, MRP, Mfg. license No. as per BPR & master price list.
Perform in process after line clearance has been given & record the same.
Tablet – I
| S. No. | Stage | IPQA Checks | No. of sample | Frequency |
| 1 | Before Washing Of Vials | PW Quality, WFI Quality,& Compressed Air Pressure Quality | Approximate 100ml each | Prior to vial washing operation. |
| After vial washing | Visible & sub visible particulate matter | 25 vials/12vials | At the start of the batch | |
| 5 Vials | At the start and every 2 hrs (visible) | |||
| At the start and every 4 hrs(sub visible) | ||||
| 3 | Vial sealing | Seal integrity & leak test | 1 vial from each sealing station | At the start and every 2 hrs |
| Reconstitution | 5 vials | At the start and every 4 hrs | ||
| 4 | Vial filling | Weight variation for filled vials | 24 vials for single dosing &12 vials for double dose | At the start and every 1 hrs |
| Visible & sub visible particulate matter | Initially Required vials for both visible and sub visible | Required vials for both visible and sub visible particles from every change over of API container. | ||
| 5 | Vial inspection | Clarity testing | 20 vials | At the start and every 2hrs |
| 6 | Packing | Vial label overprinting quality, carton overprinting quality, shipper packing. | As per BPR | At the start and every 2hrs and at the end of the process. |