- In-process specifications and test procedures along with the acceptance criteria shall be prepared for each product.
- The in-process analysis shall be carried out at different stages such as dry mixing, drying, blending, lubrication, compression/filling (capsules and powder filling), coating, and packaging operations as per the requirements.
- In-process sampling and analysis are basically divided into two sections:
- In-process, semi-finish, and finish sample intimation slip generated by production/pilot plant.
- In-process analysis is carried out by quality assurance during routine production activity.
- In-process analysis request cum report raised by production/pilot plant:
- Production/Pilot plant shall intimate to quality assurance for sampling at various stages during production for QC analysis as per SOP on Sampling of semi-finished product respective Annexure.
- Before proceeding with the sampling activity, the QA person shall ensure the preparatory setup for a sampling of semi-finished product, finished product, and rinse water/swab test samples to be carried out as per respective SOPs.
- For process validation, the QA person shall carry out the sampling as per the process validation protocol or as mentioned in the BMR and for routine manufacturing. QA person shall carry out the sampling as per respective SOPs.
- After sampling for QC analysis, the details of the samples withdrawn shall be entered in the in-process logbook as per Annexure-I and respective batch manufacturing/packing records.
- The samples shall be then forwarded to the QC department along with the Sampling Intimation Slip in duplicate for testing of the analytical parameters as per the established specifications.
- All Sampling Intimation slips shall have a QC reference number which is allotted by QC at the time of receipt of the sample and the request as per SOP for Allotment of Analytical Reference Number.
- The physical parameters of In-process samples (e.g. DT, moisture analysis, weight variation etc.) shall be checked by QA personnel and the analytical parameters (e.g. Assay, Content uniformity, Microbial analysis, Water content, LOD, bulk density, tapped density, Dissolution etc.) shall be checked in QC as per the specifications and standards.
- After completion of analysis, results shall be recorded in the sampling intimation slip by QC.
- After completion of the Finish product, analysis report shall be sent to QA for final review and approval. The QA person shall check the results for compliance and then hand over the report to the production department.
- In-process tests carried out during routine work:
- In addition to the analysis of the tests requested by the Production/Pilot plant, QA shall carry out the routine sampling and testing of the batches manufactured.
- Sampling and testing shall include in-process tests during granulation, tablet compression, coating, capsule filling, powder filling, packing operations etc.
- All the tests conducted during the above-mentioned processes shall be recorded in the respective formats as mentioned under List of Annexures. Critical parameters during in-process check are LOD, weight variation, filled weight, hardness, thickness, DT, weight gain, leak test, batch overprinting detail.
Sr. No. |
Test
Parameters |
Sample
Quantity |
Procedure |
Sample
Frequency |
1. |
Appearance /Description for tablets |
5 tablets from each batch |
Check for defects like surface
finish, lamination, mottling, chipping and swelling powder on the tablets
embossing (if any), picking, capping and sticking. The appearance of the
tablets should comply with that mentioned in the individual specification. |
Initial, every 2 hours and at the
end of the batch. |
2. |
Appearance / Description for capsules |
20 capsules |
Take about 20 capsules at random
check for defects like dented capsules, telescopic capsules, empty capsules,
capsules with notch, printing quality, crust / lump formation in the blend,
improper colour distribution of the blend, powder leaking from the locking
end and powder on capsules. The appearance of the capsules should comply with
that mentioned in the individual Specification. |
Initial, every 2 hours and at the
end of the batch |
3. |
Appearance / Description for dry
syrup |
1 bottle |
Examine for lump formation,
caking, quality of suspension odour. The appearance should comply with that
mentioned in the individual specification. |
Initial, every 2 hours and at the
end of the batch |
4. |
Appearance / Description for blend |
Visual inspection of sample collected
for QC analysis |
Examine for colour, lumps
formation. The appearance should comply with that mentioned in the individual
specification. |
Final blending or as per specification |
5. |
Disintegration time testing for tablets |
6 tablets |
Operate the disintegration tester as per SOP. Place 1 dosage unit in each of the six tubes of the basket and, if
prescribed add a disk. Operate the apparatus, using water or the specified
medium as the immersion fluid, and maintain the temperature at 37±2ºC or given in the specification. At the end of the time limit specified, lift the basket from
the fluid, and observed the tablets. All of the tablets have disintegrated
completely. If 1 or 2 tablets fail to disintegrate completely, repeat the
test on 12 additional tablets. The requirement is met if not less than 16 of
the total of 18 tablets are disintegrated. The displayed disintegration time
shall be reported in terms of minutes by converting the seconds in to minutes For Example: Suppose the display shows
the time of 4:32 this indicates the disintegration time is 4 minutes and 32
seconds while reporting 32 seconds shall be converted to minutes by dividing
32 by 60. So the reported time shall be 4.53 minutes. |
Initial, every 2 hours and at the
end of the batch |
6. |
Disintegration time testing for capsules |
6 capsules |
Introduce 1 capsule into each
tube and operate the disintegration tester as per the respective SOP. Insert disk
over each capsule. Operate the apparatus, using water or the specified medium
as the immersion fluid, and maintain it at 37±2ºC. At the end of the time limit, specified Capsules pass the test if all of them disintegrate completely. Result reporting is the same as for tablets. |
Initial, every 2 hours and at the
end of the batch |
7. |
Friability test |
For tablets with a unit mass equal to
or less than 650 mg, take a sample of Whole Tablets Corresponding to 6.5 g.
For Tablets with a Unit mass of More Than 650 mg, take a sample of 10 Whole Tablets. |
The tablets should be Carefully de-dusted
prior to testing. Accurately weigh the tablets sample, and place the tablets in
the drum. Rotate the drum 100 times, and
remove the tablets. Remove any loose dust from the tablets and accurately
weigh. Operate friability test apparatus as per respective SOP. |
Initial, every 2 hours and at the
end of the Batch. |
8. |
Hardness Testing |
6 tablets |
Hardness test shall be performed
with the help of tablet hardness tester as per respective SOP. |
Initial, every 2 hours and at the
end of the batch. |
9. |
Thickness testing for compressed/ coated
tablets |
6 tablets |
Thickness shall be determined
using an vernier caliper/ digital tablet hardness tester as per respective SOP |
Initial, every 2 hours and at the
end of compression/ At the end of each coating lot |
10. |
Weight variation (For uncoated tablets) |
1 tablet from each station of the compression
machine |
Weigh individually all tablets, and calculate the average weight. Using analytical balance as per respective. |
Initial, every 2 hours and at the
end of the batch |
11. |
Weight gain of coated tablets |
100 tablets |
Take the weight of 100 pre-warmed
tablets and weigh the 100 coated tablets. Calculate the weight gain. |
At the end of each coating lot |
12. |
Weight variation (For capsules) |
20 capsules |
Weigh 20 intact capsules
individually and determine the average weight. Remove the contents of each
capsule with the aid of a small brush or plug of cotton. Weigh the emptied
shells individually and calculate for each capsule the net weight of its
content by subtracting the weight of the shell from the respective gross weight, and determining the average net content from the sum of the individual net weights. |
Initial, every 2 hours and at the
end of the Batch. |
13. |
Lock length of the capsules |
6 capsules |
Lock length of the capsules shall
be determined using an vernier caliper as per respective SOP. |
Initial, every 2 hours and at the
end of the batch |
14. |
Loss on drying (Powders / Granules) |
Approximately 2 g or as per specification |
Determine the loss on drying with
the help of IR moisture analyzer as per SOP on Operation of Moisture Analyzer |
End of drying or as per the specification |
15. |
Fill weight of dry syrups |
No. of bottles filled while single
rotation of dosing wheel |
Take Bottles directly from the dry
syrup filling machine and check the fill weight of powder. |
Initial, every 2 hours and at the
end of the batch |
16. |
Leak Test |
Strips from 1 rotation of CSR / Blisters from sealing plate
sealed per stroke/2 bottles (in case of induction sealing)/ Bottles equal to
no. of sealing head. |
Leak test shall be performed as per respective SOP. |
Initially and every 2 hours. |
17. |
Non-Fill Detection |
One tablet/ capsule from each position
of sensor track |
Remove one tablet/ capsule each
from the pockets from each position of the sensor track. Check the blisters
whether they are rejected |
Initial and After every 2 hrs. |
18. |
Overprinting details |
Random sampling |
Visually check the blister,
strips, carton, label for batch details, wrinkles, proper pasting,
appearance, etc. |
Initial and every two hour |
19. |
Bottle / Jar Cleanliness |
Two bottles/Jar |
Visually check the bottles/Jar for
their cleanliness |
Initial and every 2 hrs. |
20. |
Tablet Count |
Random sampling |
Visually check the counts of the
tablets as per the pack size mentioned in the BPR. |
Initial and every 2 hrs. |
21. |
Desiccant insertion |
Two Jars |
Visually check the number of the
desiccants and insertion of as mentioned in the BPR. |
Initial and every 2 hrs. |
22. |
Induction sealing |
Two bottles/jars |
Visually check for the induction
sealing and ensure that it is okay. |
Initial and every 2 hrs. |
23. |
Labeling |
Random sampling |
Visually check the labeling for
any defects like Wrinkles /crumpled/ slanted/ stained or any other abnormal
observations. |
Initial and every 2 hrs. |
24. |
Leaflet Placement |
Two bottles/jars |
Visually check whether the leaflet
is placed correctly on the bottle cap/ inside the cartons. (as applicable) |
Initial and every 2 hrs. |
25. |
Measuring Cup Placement |
Two bottles |
Visually check whether the
Measuring Cup is placed correctly on the bottle. |
Initial and every 2 hrs. |
26. |
Tests to be conducted during blister
and strip packing |
Random sampling |
Visually check for any punctures,
empty pocket, overprinting details, sealing quality, knurling quality,
forming quality, sealing and forming plate and roller temperature. |
Initial and every 2 hrs. |
27. |
Carton packing |
Random sampling |
Visually check for the correct
coding, Product details, and weight of the Carton. |
Initial and every 2 hrs |
28. |
Tests to be conducted during shipper
packing |
Random sampling |
Visually check for the correct
coding, a number of unit packed, proper BOPP taping, shipper number and weight
of the shipper. |
Initial, every 2 hrs and at the
end of the batch. |
29. |
Wad sensor for Induction caps |
1 bottle and cap |
Remove aluminum wad of cap mark it
and pass Bottle and cap through wad sensor. Check the bottle whether it is
rejected. |
Initial |
30. |
Metal detector challenge test |
Ferrous non ferrous and S.S. blocks. |
Pass ferrous non-ferrous and S.S.
blocks through metal detector. Check the blocks whether it is rejected. |
initial |
31. |
Uniformity of Dispersion |
Two tablets |
Place two tablets in 100ml of
water and stir gently until completely dispersed. A smooth dispersion is obtained
which passes through a sieve screen with a nominal mesh aperture of 710μm
(sieve no.22). |
Initial and every 2 hrs |
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