1.0 OBJECTIVE: To lay down a procedure for in-process checks during the manufacturing of tablets.
2.0 SCOPE: This SOP is applicable for in-process checks during the manufacturing of tablets.
3.0 RESPONSIBILITY: Operator, Officer, Executive – Production Department
Manager – Production Department
4.1 Granulation
4.1.1 Check the cleanliness of the area.
4.1.2 Check the relative humidity, temperature, and differential pressure of the area.
4.1.3 Check the dispensed material respective to BMR.
4.1.4 Ensure status labels are affixed on all the machines and accessories.
4.1.5 Transfer the sieve as per the instruction given in BMR.
4.1.6 Check the integrity of the sieve before and after the sifting activity.
4.1.7 Check the temperature of the binder solution.
4.1.8 Transfer the screen as per the instruction given in BMR.
4.1.9 Check the integrity of the screen before and after the milling activity.
4.1.10 Check the ampere reading at the endpoint granulation.
4.1.11 Use Product dedicated FBD finger bag and RMG filter bag.
4.1.12 Check the pre and post-integrity of the FBD finger bag and RMG filter bag.
4.1.13 Check the loss on drying of granules during the dying operation.
4.1.14 Ensure that sized granules are collected in the right capacity blender bin for lubrication.
4.1.15 Ensure the blending time and RPM are as per BMR specifications.
4.1.16 Check the yield of sifted and milled granules and lubricated granules.
Note: Ensure that the granules in the S.S. container are lined with double poly bags & transfer the containers to granules quarantine.
4.2 Compression
4.2.1 Check the cleanliness of the area.
4.2.2 Check the relative humidity, temperature, and differential pressure of the area.
4.2.3 Check the die punch set as per specification in the respective BMR.
4.2.4 Ensure status labels are affixed on all the machines and accessories.
4.2.5 Check the weight and thickness of individual tablets from all compression stations for a total number of punch sets.
4.2.6 Check the weight variation, thickness, hardness, friability, and disintegration time as per specifications in respective BMR.
4.2.7 Perform challenge test with ferrous and non-ferrous test samples pieces for metal detector at the start of operation and after every 4 hours (If applicable).
4.2.8 Check the yield of compressed tablets.
Note: Ensure that the compressed tablets in the S.S. container are lined with double poly bags & transfer the containers to compressed tablet quarantine.
4.3 Coating
4.3.1 Check the cleanliness of the area.
4.3.2 Check the relative humidity, temperature, and differential pressure of the area.
4.3.3 Ensure status labels are affixed on all the machines and accessories.
4.3.4 Check the filtration of the coating solution in muslin cloth.
Note :
- After filtration, if any foreign particles or black particles are observed on the nylon cloth, stop the activity and inform to QA department for further action.
- Both QA and production shall investigate the situation observed and the same shall be recorded.
- If not satisfactory, destroy the solution and record it in the BMT.
4.3.5 Observe the Inlet, bed, and exhaust temperature every 30 minutes.
4.3.6 Check the cylinder air pressure for all guns shall be approximately the same at all times.
4.3.7 Ensure proper spraying from the individual guns.
4.3.8 Check the weight gain every 30 minutes during the coating operation.
4.3.9 Check the individual weight of 20 tablets after the coating operation.
4.3.10 Check the disintegration time of coated tablets as per specifications in respective BMR.
4.3.11 Check the thickness of coated tablets.
Note: Ensure that the compressed tablets in the S.S. container are lined with double poly bags & transfer the containers in coated tablet quarantine.
4.4 Capsule Filling
4.4.1 Check the cleanliness of the area.
4.4.2 Ensure status labels are affixed on all the machines and accessories.
4.4.3 Check the relative humidity, temperature, and differential pressure of the area.
4.4.4 Check the Appearance, weight variation, Locking length, and disintegration time as per specifications in respective BMR.
4.4.5 Check the yield of the Filled capsules.
4.5 Inspection
4.5.1 Check the cleanliness of the area.
4.5.2 Ensure status labels are affixed on all the machines and accessories.
4.5.3 Check the relative humidity, temperature, and differential pressure of the area.
4.5.4 Check the weight of rejected and passed tablets.
Note: Ensure that the compressed tablets in the S.S. container are lined with double poly bags & transfer the containers in tablet quarantine.
4.6 Packing
4.6.1 Check the cleanliness of the area.
4.6.2 Check the relative humidity, temperature, and differential pressure of the area.
4.6.3 Ensure status labels are affixed on all the machines and accessories.
4.6.4 Check the relative humidity and temperature of the blister/strip/ sachet/bulk packing room.
4.6.5 Forming temperature of the blister packaging machine is to be checked after every hour.
4.6.6 The sealing temperature of the blister/strip/sachet machine is to be checked after every hour.
4.6.7 Leak test of blisters /strips /sachets to be checked at the startup and after every two hours.
4.6.8 Printed text matter to be checked after each change of roll/joint.
4.6.9 First specimen copy of over-printed label attached to BPR after verification by IPQA.
4.6.10 100% visually check for the overprinted carton.
4.6.11 100% visual checking of pack inserts and blisters/strips before packing.
4.6.12 Entire quantity of aluminum foil / PVC of one batch was verified and transferred to the Primary packing area.
4.6.13 Initial specimen aluminum foil/blister with printing/embossing to be attached to BPR after approval by IPQA.
4.6.14 Sample of foil at every change of printed roll/joint in roll verified and attached to BPR.
4.6.15 Check the width and color of the PVC / PVC-PVDC.
4.6.16 Initial specimen of overprinted carton attached to BPR after approval by IPQA.
4.6.17 Overprinted cartons stored under lock and key.
4.6.18 100% visually check for the package inserts.
4.6.19 Ensure that during breaks no tablet should present in the web /chute of the machine
Note: All in-process parameters are checked against the limits given in the BMR. In Case of any abnormality found during the in-process checks, isolate the material processed after the last successful in-process check. Stop the machine and inform to department head and Quality Assurance department for necessary corrective action.
4.7 If any parameter during manufacturing is out of specification or out of range, the observation shall be circled to highlight the reading.
Related: SOP for the operation of Multimill
5.0 ABBREVIATION(S):
BMR: Batch Manufacturing Record.
BPR: Batch Packing Record
FBD: Fluidized bed Drier
RMG : Rapid Mixer Granulator
PVC: Poly Vinyl Chloride
PVDC: Poly Vinyl Dichloride
QA: Quality Assurance.
SOP: Standard Operating Procedure.
SS: Stainless Steel