In-process checks during Dry powder injection manufacturing & packing (IPQA)
Objective: : To lay down a procedure for in process checks during Dry powder injection manufacturing & packing.
Scope: This procedure is applicable to formulation Plant of pharmaceutical Industry for in process checks during Dry powder injection manufacturing & packing.
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
All the tests conducted shall be recorded.
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, 25 washed vials shall be 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 particles, bacterial endotoxin. It should be recorded in BMR. Sterilization operation may be continued further but batch filling shall be started only after getting line clearance from QC.
Water sample of after completing rubber bung washing cycle shall be checked for particulate matter before starting sterilization cycle & recorded in BMR
Vial filling & Bunging
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 QA person shall initially check 5 vials for its solubility & particulate matters for API from each container used during the filling and attach the reports with BMR.
Vials shall be taken from each station for in process checks.
If parameters of the filled vials are in the specified norms of BMR, further operation of in process checks shall be allowed.
Weight variation of vials shall be checked every 2 hrs. as per sampling plan & recorded.
Visible & sub visible particles shall be checked by collecting 5 vials every 4 hrs. & recorded in BMR.
Sealed Vials shall be checked for leak test initially by taking 7 vials & thereafter every 2 hrs. & shall be recorded.
Furthermore sealed vials shall be checked for defects like sealing defects, crack vials, flip off defects etc. on every 2 hrs. & shall be recorded.
Labeling & 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 arrangement from Standard Packing Arrangement (SPA) 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 B.No., MFG date, EXP date, MRP, Mfg. lic. No. as per BPR & master price list.
Perform in process checks every 2 hrs. after line clearance has been given & record the same.
In-Process Control: Injectable – Frequency: Every 2 hours
Vial sealing : Seal integrity & Leak test
Vial filling : Visible & sub visible particulate matter.
Vial inspection : Clarity testing
In process sampling plan
| Stage | IPQA Checks | No. of sample | Frequency |
| Before Washing of Vials | PW Quality, WFI Quality, Compressed Air Pressure & Compressed Air Quality | 100 ml each | Prior to vial washing operation |
| After vial washing | Visible & sub visible particulate matter | 25 vials for LBPC | At the start of the batch |
| Vial sealing | Seal integrity & leak test | 1 vial each from sealing station (7 sealing station) | Every 2hrs |
| Vial filling | Weight variation for filled vials | 24 vials for single dosing & 12 vials for double dose | Every 2hrs |
| Visible & sub visible particulate matter | Initially 5 filled vials | Every 2hrs & Every change over of API container | |
| Vial inspection | Clarity testing | 20 vials | Every 2hrs |
| Packing | Vial label overprinting quality, carton overprinting quality, shipper packing. | One sample each | Every 2hrs |
In process checks: Packing
Over Printing Text – Vial labels ,Carton & Outer
Physical Checks
Defective vials
No. of units checked
In-process sheets are completed
Final pack report completed
Whether over coding / printing packaging material are checked properly w.r.t. MRP, Batch record and specimen attached to BMR
Whether control sample withdrawal intimation report given to BSR.
Whether packed shipper are checked randomly with sign.