SOP on In-process Sampling

and Analysis of Oral Drug

Products
1.0 Objective:

1.1 To lay down the procedure for in-process sampling and analysis of oral
drug products during manufacturing.

2.0 Scope:

2.1 This procedure is applicable for in-process sampling, analysis and

reporting to be carried out during manufacturing of drug products at
formulation Plant.

3.0 Responsibility:

3.1 Quality Assurance department.

4.0 Accountability:

4.1 Head-QA shall be accountable for compliance of SOP.

5.0 Procedure:

5.1 In-process specifications and test procedures along with the acceptance
criteria shall be prepared for each product.
5.2 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.

5.3 In process sampling and analysis is basically divided into two

sections:

5.3.1 In process, semi-finish and finish sample intimation slip generate by

production / pilot plant.

5.3.2 In process analysis carried out by quality assurance during routine

production activity.

5.4 In process analysis request cum report raised by production/

pilot plant:

5.4.1 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.

5.4.2 Before proceeding for the sampling activity, QA person shall ensure
the preparatory set up for sampling of semi-finished product, finished
product and rinse water / swab test samples to be carried out as per
respective SOPs.

5.4.3 For process validation 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.
5.4.4 After sampling for QC analysis, the details of the samples withdrawn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 record.

5.4.5 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.

5.4.6 All Sampling Intimation Slip shall have 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.

5.4.7 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.

5.4.8 After completion of analysis, results shall be recorded in the sampling

intimation slip by QC.

5.4.9 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 then hand over the report to the production department.

5.5 In process tests carried out during routine work:

5.5.1 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.
 5.5.2 Sampling and testing shall include in process tests during granulation,
tablet compression, coating, capsule filling, powder filling, packing
operations etc.

5.5.3 All the tests conducted during the above mentioned processes shall be
recorded in the respective formats as mentioned under Point number 6.0
‘List of Annexure / Formats’. Critical parameters during in process check are
LOD, weight variation, filled weight, hardness, thickness, DT, weight gain,
leak test, batch overprinting detail.

5.5.4 The in-process tests including the frequency of testing are mentioned
in the table 1:

S.N Test Sample Sample

Procedure Reporting
o. parameters quantity Frequency
Check for defects like
surface finish, lamination,
mottling, chipping and
Initial,
swelling powder on the
1. Appearance every 2
5 tablets from tablets embossing (if any),
/Description hours and at Annexure-II
each batch picking, capping and
for tablets the end of
sticking. The appearance of
the batch.
the tablets should comply
with that mentioned in the
individual specification.
Take about 20 capsules at
random check for defects
like dented capsules,
telescopic capsules, empty
capsules, capsules with
Initial,
notch, printing quality,
Appearance / every 2
crust / lump formation in
2. Description for 20 capsules hours and at Annexure-III
the blend, improper colour
capsules the end of
distribution of the blend,
the batch
powder leaking from the
locking end and powder on
capsules. The appearance of
the capsules should comply
with that mentioned in the
S.N Test Sample Sample
Procedure Reporting
o. parameters quantity Frequency
individual Specification
Examine for lump
Initial,
formation, caking, quality
Appearance / every 2
of suspension odour. The
3. Description for 1 bottle hours and at Annexure-IV
appearance should comply
dry syrup the end of
with that mentioned in the
the batch
individual specification.
Examine for colour, lumps Final
Visual
Appearance / formation. The appearance blending or
inspection of
4. Description for should comply with that as per Annexure-I
sample collected
blend mentioned in the individual specificatio
for QC analysis
specification. n
Operate the disintegration
tester as per SOP number
QA-SG-006. Place 1 dosage
unit in each of the six tube
of the basket and, if
prescribed add a disk.
Operate the apparatus,
using water or the specified
medium as the immersion
fluid, maintain temperature
at 37+2ºC or given in
specification. At the end of
the time limit specified, lift
Initial,
the basket from the fluid,
every 2
Disintegration and observed the tablets.
hours and at
5. time testing for 6 tablets All of the tablets have Annexure-II
the end of
tablets disintegrated completely. If
the
1or 2 tablets fail to
batch
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
S.N Test Sample Sample
Procedure Reporting
o. parameters quantity Frequency
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.
Introduce 1 capsule in to
each tube and operate the
disintegration tester as per
respective SOP. Insert disk
over each capsule. Operate
Initial,
the apparatus, using water
every 2
Disintegration or the specified medium as
hours and at
6. time testing for 6 capsules the immersion fluid, Annexure-III
the end of
capsules maintain at 37+2ºC. At the
the
end of the time limit
batch
specified Capsules pass the
test if all of them
disintegrate completely.
Result reporting is same as
for tablets.
Tablets with a
unit mass equal The tablets should be
to or less than Carefully de-dusted prior to
650 mg, take a testing. Accurately weigh
sample of the tablets sample, and
Initial,
Whole Tablets place the tablets in the
every 2
Corresponding drum. Rotate the drum 100
hours and at
7. Friability test to 6.5 g. For times, and remove the Annexure
the end of
Tablets with a tablets. Remove any loose
the
Unit mass of dust from the tablets and
Batch.
More Than accurately weigh.
650 mg, Operate friability test
take a sample apparatus as per respective
of 10 Whole SOP.
Tablets.
Initial,
Hardness test shall be
every 2
Hardness performed with the help of
8. 6 tablets hours and at Annexure-II
Testing tablet hardness tester as per
the end of
respective SOP.
the batch.
S.N Test Sample Sample
Procedure Reporting
o. parameters quantity Frequency
Initial,
every 2
Thickness shall be
Thickness hours and at
determined using vernier
testing for the end of
9. 6 tablets caliper/ digital tablet Annexure-II
compressed/ compressio
hardness tester as per
coated tablets n/ At the
respective SOP
end of each
coating lot
Weigh individually all Initial,
1 tablet from
Weight variation tablets, calculate the every 2
each station of
10. (For uncoated average weight. Using hours and at Annexure-II
compression
tablets) analytical balance as per the end of
machine
respective. the batch
Take weight of 100 pre
At the end
Weight gain of warmed tablets and Weigh
11. 100 tablets of each Annexure-II
coated tablets the 100 coated tablets.
coating lot
Calculate the weight gain.
a) Weigh 20 intact capsules
individually and determine
the average weight.
b) Remove the contents of
each capsule with the aid of
small brush or plug of Initial,
cotton. Weigh the emptied every 2
Weight
shells individually and hours and at
12. variation 20 capsules Annexure-III
calculate for each capsule the end of
(For capsules)
the net weight of its content the
by subtracting the weight of Batch.
the shell from respective
gross weight, determine the
average net content from
the sum of the individual
net weights.
Initial,
Lock length of the capsules
every 2
Lock length of shall be determined using
13. 6 capsules hours and at Annexure-III
the capsules vernier caliper as per
the end of
respective SOP.
the batch
Determine the loss on End of
Loss on drying Approximately 2
drying with the help of IR drying or as In BMR if
14. (Powders / g or as per
moisture analyzer as per per the applicable
Granules) specification
SOP on Operation of specificatio
S.N Test Sample Sample
Procedure Reporting
o. parameters quantity Frequency
Moisture Analyzer n
Initial,
No. of bottles Take Bottles directly from
every 2
Fill weight of filled while the dry syrup filling
15. hours and at Annexure-IV
dry syrups single rotation of machine and check the fill
the end of
dosing wheel weight of powder
the batch
Strips from 1
rotation of CSR
/blisters from
sealing plate
sealed per Leak test shall be Initially and
Annexure-IV,
16. Leak Test stroke/2 bottles performed as per respective every 2
Annexure-V
(in case of SOP. hours.
induction
sealing)/ Bottles
equal to no. of
sealing head.
Remove one tablet/ capsule
One tablet/
each from the pockets from Initial and
Non Fill capsule from
17. each position of the sensor After every Annexure-VI
Detection each position of
track. Check the blisters 2 hrs.
sensor track
whether they are rejected
Visually check the blister,
strips, carton, label for Initial and Annexure-V
Overprinting Random
18. batch details, wrinkles, every two Annexure-VI
details sampling
proper pasting, appearance, hour Annexure-VII
etc.
Visually check the
Bottle / Jar Initial and Annexure-VI
19. Two bottles/Jar bottles/Jar for their
Cleanliness every 2 hrs. Annexure-VII
cleanliness
Visually check the counts
Random of the tablets as per the Initial and
20. Tablet Count Annexure-V
sampling pack size mentioned in the every 2 hrs.
BPR.
Visually check the number
Desiccant of the desiccants and Initial and
21. Two Jars Annexure-VI
insertion insertion of as mentioned in every 2 hrs.
the BPR.
Visually check for the
Induction Initial and Annexure-VI
22. Two bottles/jars induction sealing and
sealing every 2 hrs. Annexure-VII
ensure that it is okay.
S.N Test Sample Sample
Procedure Reporting
o. parameters quantity Frequency
Visually check the labeling
for any defects like
Random Initial and Annexure-VI
23. Labeling Wrinkles/ crumpled/
sampling every 2 hrs. Annexure-VII
slanted/ stained or any other
abnormal observations.
Visually check whether the
Annexure-V
Leaflet leaflet is placed correctly on Initial and
24. Two bottles/jars Annexure-VI
Placement the bottle cap/ inside the every 2 hrs.
Annexure-VII
cartons.(as applicable)
Visually check whether the
Measuring Cup Initial and
25. Two bottles Measuring Cup is placed Annexure-VII
Placement every 2 hrs.
correctly on the bottle.
Visually check for any
Tests to be punctures, empty pocket,
conducted overprinting details, sealing
Random Initial and Annexure-V
26. during blister quality, knurling quality,
sampling every 2 hrs.
and strip forming quality, sealing and
packing forming plate and roller
temperature.

Visually check for the

Annexure-V
Random correct coding, Product Initial and
27. Carton packing Annexure-VII
sampling details, and weight of the every 2 hrs
Carton.

Visually check for the Initial,

Tests to be
correct coding, number of every 2 hrs Annexure-V
conducted Random
28. unit packed, proper BOPP and at the Annexure-VI
during shipper sampling
taping, shipper number and end of the Annexure-VII
packing
weight of the shipper. batch.
Remove aluminum wad of
cap mark it and pass Bottle
Wad sensor for
29. 1 bottle and cap and cap through wad Initial Annexure-IV
Induction caps
sensor. Check the bottle
whether it is rejected.
Pass ferrous non ferrous
Ferrous non and S.S. blocks through
Metal detector
30. ferrous and S.S. metal detector. Check the initial Annexure-II
challenge test
blocks. blocks whether it is
rejected.
Place two tablets in 100ml
Uniformity of Initial and
31. Two tablets of water and stir gently Annexure-II
Dispersion every 2 hrs
until completely dispersed.
S.N Test Sample Sample
Procedure Reporting
o. parameters quantity Frequency
A smooth dispersion is
obtained which passes
through a sieve screen with
a nominal mesh aperture of
710µm (sieve no.22).