| In-Process Quality Checks during Filling and packing |
1.0 OBJECTIVE To lay down the procedure for in-process quality checks during filling and packing operation in sterile dry powder injection and small volume parenteral and large volume parenteral. 2.0 SCOPE This procedure is applicable for in-process quality checks during filling and packing operation in sterile dry powder injection and small volume parenteral and large volume parenteral operation. 3.0 RESPONSIBILITY • Officer or above -In-Process Quality Assurance • Officer or above – Production • Officer or above – QC/Microbiologist 4.0 ACCOUNTABILITY • Head Concerned Department • Head Quality / QA 5.0 PROCEDURE 5.1 In-process quality checks in sterile dry powder injection: 5.1.1 Washing of Vials: 5.1.1.1 At the start of vial washing initially check 08 washed each grippers& check vials visually for Particulate matters after filling with particle free WFI against visual inspection hood having black & white background. Repeat the process after every two hours and record it in the batch records. 5.1.1.2 Collect the 10 washed vials randomly during washing and send them to QC dept for Bioburden (Frequency – once in 15 days). 5.1.1.3 Collect water of injection samples before washing for clarity check and record it in the batch records. 5.1.2 Sterilization of Vials: (Tunnel Sterilizer) 5.1.2.1 Check and ensure that the tunnel temperature is maintained at 310 – 330°C throughout sterilization process. 5.1.2.2 After sterilization collect 10 vials and sent to QC for sterility and Endotoxin test. (Frequency – once in 15 days.) 5.1.2.3 Check and ensure that the differential pressure of filling room and washing area is within limit 10 Pa to 40 Pa. Record the details for every two hours. 5.1.2.4 Collect 10 empty vials after sterilization for visual and clarity checking before starting the filling. 5.1.3 Rubber Stoppers Washing and Sterilization: 5.1.3.1 Washed rubber stoppers (approx. 30 No’s) are collected in to a bottle containing filtered WFI and shake. Visually check and ensure that the water should be free from any foreign particles. This should be monitored for each load of rubber stoppers. The rubber stoppers are sterilized in bung processor. Check that the sterilization temperature is maintained at 121.5°Centigrade – 124°Centigrade for 30 minutes. 5.1.3.2 20 numbers of rubber stopper of each lot shall be sent for moisture content on daily basis, sterility and endotoxin test to be performed once in 15 days. 5.1.4 Vial Filling and Sealing: 5.1.4.1 Verify the calculation for target fill weight of batch on the basis of assay and water content / LOD in BMR/BPR. 5.1.4.2 Collect the 24 filled vials from individual piston according to port wheel position and check the weight variation of filled contents individually by emptying the contents from vials using a calibrated weighing balance, weight record in the BMR. The Average weight and weight variation shall be within the specified limits as mention in respective in process specification of each product. If the weight variation is found, out of limit, stop the machine and segregate the filled vials between previous and current check. Randomly collect 20 vials from segregated filled vials/packed and perform weight variation. NMT 2 out of 20 vials deviated from the average weight by more than 10% and non deviate by more than 20 %. Clear the vials if weight variation is found within the limits otherwise reject the filled vials. Get the machine rectified from the production operator and recollect the sample and check. If all the filled vials are found within the specification limit, allow the machine for further filling. (Limit: For Individual port: ± 2% of Theoretical fill weight, For Average weight: ± 5 % of theoretical fill weight.) 5.1.4.3 Collect 15 filled sealed vials from the continuous running machine and check the Vials for physical observation. Perform this activity after every one hour. Noted that the vials should be placed in upright positions. No loose sealing, any collar/dent should be there. Sealing should be satisfactory. In case of failure, get the machine rectified from the production operator. Collect 15 vials (1 from each sealing head) and perform leak test, after getting clearance from IPQA start the sealing activity. 5.1.4.4 In case of aseptic area, where processing can be seen from view panel or outside of aseptic area/corridor, in process checks shall be done by operator and same shall be recorded and signed by production/QA officer in batch record. 5.1.5 Labeling and Coding: 5.1.5.1 Check10 vials for every one hour by IPQA and production alternately for Batch No., Mfg. Date, Exp. Date, MRP, Cross Labeling, and Mfg. Lic. No. and Text matter. If all are complying, then record it in respective batch records. 5.1.5.2 Check 10 printed cartons for every one hour by IPQA and production alternately for Batch No., Mfg. Date, Exp. Date, MRP, Smudging, Mfg. Lic. No. and Text matter. If all are complies then record it in respective batch records. 5.1.6 Packing: 5.1.6.1 After receiving intimation from Head Production, the Packaging In-charge shall arrange finished product vials and other packaging material at defined packing line as per Bill of Material. 5.1.6.2 The details product information shall be cross verified by the Packaging supervisor and IPQA Officer based on the BPR. 5.1.6.3 Trained inspector shall be arranged to verify all the vials regarding any dirty vials, defected like mould defect, vial breakage, cracks, seal defect, seal without rubber bungs. 5.1.6.4 The vials for cleaning shall be kept under crate labeled as “Vial for Inspection” and the defected vials shall be segregated and kept under crate labeled as “Rejected Vials”. The inspected vials shall be kept under the crate labeled as “Vial for Packaging”. 5.1.6.5 The packaging inspector shall be informed about the Product Name, Batch No., Mfg. Date, Exp. Date, MRP, Mfg. Lic. No., insert and other defects. 5.1.6.6 Before final packaging of consignment, packaging inspector shall inspect all the inner carton and outer carton randomly about the Product Name, Batch No., Mfg. Date, Exp. Date, MRP, Mfg. Lic. No., insert and other defects at the terminal end before shipper packaging. 5.1.7 In-Process Checks: 5.1.7.1 Collect one packed shrink or outer carton for every one hour by IPQA and production alternately. Check every mono carton, vial for Batch No., Mfg. Date, Exp. Date, MRP, Cross Labeling, and Mfg. Lic. No., Text matter, Leaflet and SWFI. If all are complies then record it in respective batch records. 5.1.8 Finished Goods Checking: 5.1.8.1 During final packing IPQA check final packed shipper as per AQL procedure. 5.1.8.2 After completing of final packing, check randomly of shippers quantity packed and quantity of product. 5.1.9 Verification/Setting of Shipper Weight Limit: 5.1.9.1 First of all note down the weight of one E-Flute /Mother Cartons/Shrink and divide the E-Flute /Mother Cartons/Shrink Wight in two parts. 5.1.9.2 Then take ten shippers weight and calculate the average weight of the same shippers. 5.1.9.3 Add half weight of mother/Shrink/e-flute weight in average weight of shipper for maximum limit and take away half weight of mother /shrink/e-flute weight from average value of shipper weight for minimum value limit. 5.2 In-process quality checks in small volume parenteral and large volume parenteral (SVP & LVP): 5.2.1 In process check during chopping area: 5.2.1.1 During in process Check in chopping area IPQA personnel shall collect the filled ampoule /bottle from each filling nozzle of filling machine and check weight of each ampoule / bottle. 5.2.1.2 First take empty ampoule / bottle weight then take filled ampoule / bottle and subtract the empty ampoule / bottle weight from filled ampoule / bottle. 5.2.1.3 Divided the observed weight with specific gravity provided in BMR after that we get filled volume of ampoule / bottle. 5.2.1.4 Filled volume shall be recorded in respective BMR. 5.2.1.5 In process check activity shall be performed by production and IPQA person as per frequency defined in BMR. 5.2.2 Packing: 5.2.2.1 Take the line clearance of packing line as per SOP and record the same in BPR. 5.2.2.2 Check and verify the over printing details over printed on label, carton and shipper by IPQA personnel. 5.2.2.3 Perform the leak test as mentioned in the SOP and record the same in respective BPR. 5.2.2.4 Perform the in process activity as per frequency defined in respective BPR. |
