SOP ON INPROCESS CONTROLS
PURPOSE: To lay down a procedure for in process control in dispensing area, oral preparation (Tablets, Capsules & Dry Syrup) and in Dry powder Injection.
SCOPE: This SOP is applicable for the Tablet Capsule dry syrup orals dosage Forms and Dry powder Injections for different products manufactured
RESPONSIBILITY:
Preparation of SOP: Officer/ Sr. Officer
Checking and Review of the SOP: Executive /Sr. Executive
Approval of SOP: Assistance Manager or his designee
Authorization of SOP: Head QA/ Designee
ACCOUNTABILITY: Head QA/ designee shall be accountable for implementation and compliance of the SOP.
PROCEDURE: QA/Production person shall inspect various in process parameters at different processing stages.
INPROCESS CONTROL IN DISPENSING AREA:
Cleanliness of working area, equipment’s and involved personnel’s, proper housekeeping shall be checked.
The areas, equipment, containers shall be checked with proper status Labels. Line clearance and proper segregation of materials, equipment’s and process shall be verified.
Temperature and relative humidity of the area shall be verified.
Verify whether persons handling materials is using hand gloves, uniform and nose mask or not.
The dispensing operations shall be checked for its compliance with respective BMR. Following points shall be checked.
Verification of weight balance and its calibration status.
Raw materials: its quantity, identification, physical status/ dispensing labels.
Machine being used is identified on properly set using proper accessories etc.
Documentation is being done simultaneously.
Ensure the cleaning & availability of dispensing accessories i.e. barrel pump, Scoops, etc.
TABLET: INPROCESS CHECKS DURING PROCESSING:
Dry Mixing: Visually Check the Active ingredients & Excipients, it should be uniform mixed. Then send the sample to QC for blend uniformity analysis.
Granulation: Granulation process simply involves wet massing of the powder blend with a granulating liquid to produce granules with different physical properties. Check the mixing time and speed during granulation process.
Milling: wet granulation might need to be milled to break up and enhance drying of the granulation. Check the mill speed, Screen size and its integrity as per BMR.
Drying: The optimal moisture content of the dried granulation needs to be determined. High moisture content can result in tablet picking or sticking to tablet punch surfaces and poor chemical stability as a result of hydrolysis. An over dried granulation could result in poor hardness and friability. So check the drying time during drying process and moisture content after drying process.
Lubrication: To reduce the friction during tablet ejection between the wallsof the tablet and die cavity. Check in process control Bulk Density, Particle Size distribution, Moisture content after lubrication. Moisture content should be within specified limit give in the respective Batch Manufacturing Record and record the observation in the Batch Manufacturing Record.
Compression: Check the physical appearance of tablet as per specification given in respective Batch Manufacturing Record and ensure that correct punches (lower and upper punch) are used and also for any defects like sticking, Chipping, Cracking or any collar projections due to punch damage.
Thickness, diameter, length and width (capsule shaped) – check thickness and diameter of five tablets from both sides in every two hours (limit as Specifications of the tablets) by using vernier caliper and record observation in the Batch Manufacturing Record.
Hardness- checks hardness of five tablets from both sides in every two hours (limit as per specifications of the tablets) by using calibrated Hardness tester and record observation in the Batch Manufacturing Record.
Friability – check friability of 20 tablets or 6.5 gm. of tablets, whichever is less from composite samples from both the sides in every two hour. (IP limit is NMT 1%).For tablets with unit weight equal to or less than 650 mg take a sample of 20 tablets. For tablet with unit weight of more than 650 mg take a sample of 10 tablets. Check the initial weight of 20 tablets, weight of 20 tablets after friability and record observation in the Batch Manufacturing Record.
Disintegration – check disintegration time of 6 tablets with or without disk from composite sample from both the sides in every two hours. Record observation in the Batch Manufacturing Record.
| Uncoated Tablet | NMT 15 min, in water with Disc 370C ± 20C |
| Coated Tablet | NMT 30 min, In water with Disc for Film Coated Tab, and NMT 60 min Other than Film coated tablet |
| Enteric Coated Tab | Intact for 1 hr. in 0.1 N HCl & disintegrate within 2 hr. in Mixed 6.8 Phosphate buffer. |
| Dispersible/Soluble | Within 3 min in water at 15 – 250C (IP) |
| Effervescent Tab | 5 min in 200 ml water at 15-250C (IP) |
Average Weight of 20 tablets – check weight of 20 tablets from both the sides in every 30 minutes (±1% of the standard weight of 20 tablets).
Individual weight variation of tablets – check individual weight of 20 tablets from both the sides in every 2 hours equal to the number of punches rounded off the nearest value e.g. for 27 station machines, number of tablets to be Checked is 30, in every 2 hours (limit- depends on the average weight).
| IP | USP | Limit |
| 80 mg or less | 130 mg or less | 10% |
| More than 80 mg or less than 250 mg | 130 mg to 324 mg | 7.5% |
| 250 mg or more | More than 324 mg | 5% |
If any abnormality found, stop the operation and inform to the concerned Production chemist to rectify.
Coating: Check the % Weight gain of tablet at the end of coating process and colour uniformity after coating process.
Check Average weight of 20 tablets (Limit ± 1%), Individual weight Variation, Thickness, Hardness, Disintegration time (except sugarcoated) Record observation in the Batch Manufacturing Record.
Packing: QA officer shall inspect the Status Labeling of Area and Equipment. QA/Packing officer shall inspect Various in process parameters during packing.
Cutting edges of Physical appearance of the forming should be proper –During packing after every 1 hr.
Embossing should be visible and readable – During packing after every 1 hr.
Check the printed and unprinted packing material as per packing order and verify the quantity (Refer BPR).
Check the coding details w.r.t. batch no. , Mfg date, exp, Date, (ref. BPR) Check the coding details on strip, blister, Label, unit carton,
Scratch marks and spots on strips. – During packing after every 1 hr.
Chipped/capped/broken tablets- During packing after every 1 hr.
Leak Test- During packing after every 2 hr.
Correct Batch number and Mfg. and expiry embossed on the aluminum foil-once in the beginning.
CAPSULE: INPROCESS CHECKS DURING PROCESSING:
Blending: Check and ensure that machine/equipment/accessories bears the machine/Equipment/ bin container status label of current batch as per Batch Manufacturing Record.Verified that all entries are completed in BMR up to the previous stage of that activity. Verified the RH, Temperature of Blending room which should be within specified limit and record the observation in the Batch Manufacturing Record. Check the integrity of sieve visually used for sifting randomly in sifter.
Filling: Ensure that blend powder is analyzed and released before starting up the filling activity. Check that the container to be used for filling bears the product status label and is fixed on the machine at gravity feed receptor in such a way there is no spillage of powder. Verified the RH, Temperature of filling room which should be within specified limit and record the observation in the Batch Manufacturing Record. Various in process parameter is to be checked during filling stage.
Appearance, size and colour of the capsule as per specified in BMR- once in the beginning and checks at regular interval of 2 Hours.
Weight of empty capsules – check weight of 20 empty capsules-once in Beginning.
Locking length – check locking length of 10 filled capsules in every 2 hours.( limit – ± 0.5 mm of the standard value)
Individual weight variation of capsules – check individual weight variation of 20 filled capsules in every 2 hours.
| Acc. to I.P/B.P. | Limit |
| Less than 300 mg | 10% |
| 300 mg or More | 7.5% |
Weight of 20 filled capsules – check weight of 20 filled capsules in every 30 minutes (limit ± 1% of the standard value)
Disintegration – check disintegration time of 6 capsules with or without disk in every two hours.
If any abnormality found, stop the operation and inform to the concerned Production supervisor to rectify. Recheck and ensure that the parameters are within the limits record the observation in the Batch Manufacturing Record.
DRY SYRUP: INPROCESS CHECKS DURING PROCESSING: During granulation equipment used cleanliness to be checked.
During sugars drying and sifting in process check
Drying record to be filled in starting of process.
Check the mesh size, integrity of mesh before and after sifting.
Check the blender with speed as mentioned in BMR.
Bulk sample analysis to be done as per BMR.
Check the weight of the granules as per BMR.
Input material verification to be done.
Air pressure must be check at initial and every two hours
Filling and Sealing machine speed with environment condition initial every.
One hour and end process.
Check in process control of induction sealing frequency every two hours and initial and end of the process.
Check in process fill weight of bottles frequency every 30 minutes.
Check visual inspection for filled and sealed bottle.
Check sensor challenge test of labeling and carton coding initial end and every two hours.
DRY POWDER INJECTION: INPROCESS CHECKS DURING PROCESSING: Size, colour of the Vials as per specified in the BMR – Once in the beginning.
Vials decartoning and equipment cleaning in process check at starting.
Check the in-process clarity check of washed vials randomly at start and in every 2-hour interval.
Vial washing parameter in process check at every 2 hours (PW WFI compressed air pressure)
In process check during sterilization and depyrogenation every 1 hour.
Environment monitoring (RH and temperature and DP to be done every 2Hour.
In process check in weight variation at starting of filling and frequency check every alternate hour.
Temperature and RH in process every alternate hour.
Vacuum leak test: Vials from all sealing heads (8 vials from each head) should be tested for the leak test initially then every two hours.
REFERENCES
SOP for SOP
USP 40
IP2018.