sop for In Process Checks
1.0 PURPOSE
To define a procedure for in process checks to be performed during manufacturing and packing of
pharmaceutical products to ensure that all the critical parameters are within the specified limits standards. or
2.0 SCOPE
2.1 This procedure applies for in process checks to be performed during manufacturing and packing pharmaceutical products
Note: This SOP is applicable for Tablet and Hard gelatin Capsule formulations. of
3.0 REFERENCE(S) & ATTACHMENTS
3.1 References
3.1.1 Indian Pharmacopoeia
3.1.2 United States Pharmacopoeia
3.1.3 In House
3.2 Attachments
3.2.1 Nil
4.0 Abbreviations
4.1.1 IPQA : In-process Quality Assurance
4.1.2 SOP : Standard Operating Procedures
4.1.3 PPQ: Process Performance Qualification
5.0 RESPONSIBILITY:
5.1 Production and IPQA staff:
5.1.1 Performing the in-process checks during manufacturing.
5.2 Quality Assurance Head:
5.2.1 To ensure implementation of the defined procedure.
5.3 Plant Head:
5.3.1 To ensure implementation of the defined procedure.
6.0 Distribution:
I. Quality Assurance
II. Production
7.0 PROCEDURE:
7.1 Frequency and limits of in-process checks shall be as per BMR/ BPR of individual product.
7.2 Start up inprocess check will be done by IPQA person after the satisfactory inprocess check done by production person & the same activity will be recorded in respective BMR/BPR.
7.3 In -process check frequency for development and Process Performance Qualification (PPQ) batches preferably shall be twice with respect to routine commercial batches e.g. if in-process check frequency is every one hour for commercial batch then frequency for in-process checks shall be every 30 minutes for development and PPQ batches.
7.4 IPQA/production person shall ensure environmental conditions and other specified requirements are maintained throughout the activity.
7.5 IN-PROCESS CHECKS IN TABLETS:
7.5.1 IN-PROCESS CHECKS DURING GRANULATION
| Parameters | Sample type | Quantity | Frequency |
| Loss on drying (Powders /
Granules): |
Composite | 2-3 gm | After completion of drying |
| Appearance / Description for blend (for colour, odour & lump
formation) |
Composite* | 20 gm | After lubrication |
If there is only one container containing the blend, then sample shall be drawn from initial, middle & bottom of the container & composite sample will be prepared.
If more than one container are there containing the blend, then sample will be collected from each container & composite sample will be prepared.
7.5.2 IN-PROCESS CHECKS DURING TABLET COMPRESSION
| Parameters | Sample Type | Quantity | Frequency |
| Appearance / Description for tablets (for defects like surface finish crumbling, mottling, chipping, swelling, powder on the tablets embossing (if any) stickiness, capping, lamination, sticking,
burring and picking) |
Directly from the compression machine. | At the beginning and every start up: Total no. of stations + *additional no. of tablets & 20 Nos. thereafter from each side of the machine. | At the beginning & as per frequency mentioned in BMR thereafter**, every start up of machine |
| Dimension | Directly from the compression machine. | Equal to total no. of stations from each side of
the machine. |
At the beginning, every start up of machine |
| Average Weight | Directly from the compression machine. | 20 Nos. | At the beginning & as per frequency mentioned in BMR thereafter**, every start up of
machine |
| Parameters | Sample Type | Quantity | Frequency |
| Uniformity of weight | Directly from the compression machine. | At the beginning and every start up: Total no. of stations additional no. of tablets & 20 Nos. thereafter from each side
of the machine. |
At the beginning & as per frequency mentioned in BMR thereafter every
start up of machine |
| Thickness | Directly from the compression machine. | At the beginning and every start up: Total no. of stations and 10 Nos. thereafter from each side
of the machine. |
At the beginning & as per frequency mentioned in BMR thereafter**, every start up of machine |
| Hardness | Directly from the compression machine. | 10 Nos. from each side of the machine. | At the beginning & as per frequency mentioned in BMR thereafter**, every start up of
machine |
| Friability test | Directly from the compression machine. | 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. Take sample from each side of
the machine. |
At the beginning & as per frequency mentioned in BMR thereafter**, every start up of machine |
| Disintegration time | Directly from the compression machine. | 06 Nos. from each side of the machine. | At the beginning & as per frequency mentioned in BMR thereafter**, every start up of
machine |
Additional no. of tablets depends on the no. of stations of the compression machine.
For example:
Additional tablets for a 45/ 55/ 75 station machine shall be 5 nos. and for a 26/ 36 station machine shall be 4 nos. to make a next round
figure i.e. 50, 60 and 80 no. of sample in case of 45, 55 and 75 station machine respectively and 30 and 40 no. of sample in case of 26 and 36 station machine respectively.
For a batch which runs less than 4 hours, the frequency of inprocess check will be initial, middle & end of processing. For a batch which runs more than 4 hours,
the frequency of inprocess check will be every 2 hours till end of processing.
7.5.3 IN-PROCESS CHECKS DURING TABLET COATING
| Parameters | Sample Type | Quantity | Frequency |
| Appearance/Description for tablets (for defects like surface finish, crumbling, mottling, chipping, swelling, peeling, bridging, deposition in
embossing (if any), stickiness, twining) etc. |
Composite | 20 Nos. | At the end of coating |
| Dimension | Composite | 20 Nos. | At the end of coating |
| Average Weight | Composite | 20 Nos. | At the end of coating |
| Uniformity of weight | Composite | 20 Nos. | At the end of coating |
| Thickness | Composite | 20 Nos. | At the end of coating |
| Disintegration time*** | Composite | 06 Nos. | At the end of coating |
For enteric coated tablets, check the disintegration time using 0.1 M Hydrochloric acid & pH 6.8 buffer.
7.6 IN-PROCESS CHECKS IN HARD GELATIN CAPSULES:
7.6.1 IN-PROCESS CHECKS DURING BLEND:
| Parameters | Sample type | Quantity | Frequency |
| Loss on drying (Powders / Granules): | Composite | 2-3 gm | After completion of drying |
| Appearance / Description for blend (for
colour, odour & lump formation) |
Composite* | 20 gm | After lubrication |
If there is only one container containing the blend, then sample shall be drawn from initial, middle & bottom of the container & composite
sample will be prepared. If more than one container are there containing the blend, then sample will be collected from each container & composite sample will be prepared.
7.6.2 IN-PROCESS CHECKS DURING HARD GELATIN CAPSULE FILLING
| Parameters | Sample type | Quantity | Frequency |
| Appearance / Description for capsules (for defects like dented capsules, empty capsules, capsules with V-notch, printing quality, crust / lump formation in the blend, powder leaking from the locking end, powder on capsules, Chipping of sides
of capsules) |
Directly from the capsule filling machine | Nos. equal to the No. of stations at the beginning & 20 Nos. thereafter as per frequency | At the beginning & as per frequency mentioned in BMR thereafter , every start up of machine |
| Lock Length | Directly from the capsule filling machine | Nos. equal to the No. of stations at the beginning & 20 Nos thereafter as per
frequency |
At the beginning & as per frequency mentioned in BMR thereafter every start up of
machine |
| Average weight of filled capsules | Directly from the capsule filling machine | 20 Nos. | At the beginning & as per frequency mentioned in BMR thereafter , every start up of
machine |
| Uniformity of weight | Directly from the capsule filling machine | Nos. equal to the No. of stations at the beginning & 20 Nos thereafter as per
frequency |
At the beginning & as per frequency mentioned in BMR thereafter , every start up of
machine |
| Disintegration | Directly from the capsule filling machine | 06 Nos. | At the beginning & as per frequency mentioned in BMR thereafter , every start up of
machine |
For a batch which runs less than 4 hours, the frequency of inprocess check will be initial, middle & end of processing.
For a batch which runs more than 4 hours, the frequency of inprocess check will be every 2 hours till end of processing.
7.7 IN-PROCESS CHECKS DURING PRIMARY PACKING (BLISTER/STRIP PACKING) IN TABLETS AND CAPSULES
| Parameters | Details to be checked | Quantity |
| Appearance of tablets | Broken / capped/ laminated / chipped / discoloured / black particles / foreign particle /
distorted or de-shaped |
Collect the number of strips equivalent to the no. sealed on one complete rotation of the sealing roller surface. |
| Appearance of Capsules | Chipped / broken / deformed / dented capsules/ V notched capsules /Capsules with foreign material /capsules with oil stain &
Improper lock length |
Collect the number of strips equivalent to the no. sealed on one complete rotation of the sealing roller surface. |
| Foil shifting | Foil shifting reduces the sealing
width of strips and to be observed carefully. |
—– |
| Batch coding details on foil | Check the batch details as per BPR and observe the correctness of coding details, legibility of coding details, missing of letters or
smudging / lifting of ink. |
Collect the number of strips equivalent to the no. of stereos on the overprinting roller. |
| Empty Pockets/Cut pocket | Check each individual pocket of strip for the presence of tablet /
capsule and integrity of pocket. |
Collect the number of strips equivalent to the no. sealed on one complete rotation of the
sealing roller surface. |
| Proper forming of blister | The blister shall be fully formed as per the shape of the cavity of forming roller. Each strip is to be
carefully observed for any irregularity in the shape of blisters. |
Collect the number of strips equivalent to the no. sealed on one complete rotation of the sealing roller surface. |
| Proper cutting of the strips /
blisters |
Examine the strips for proper cutting. Check the horizontal & vertical cutting. | Collect the number of strips equivalent to the no. sealed on one complete rotation of the sealing roller surface. |
| Appearance of the strip | Check the strips for poor knurling, de-lamination, hologram creasing on foil (if applicable) and also faulty printing such as ink lining; ink patches, Smudging of ink and
poor legibility of printed letters. |
Collect the number of strips equivalent to the no. sealed on one complete rotation of the sealing roller surface. |
| Leak test | Perform leak test as per the respective SOP. | Collect the number of strips equivalent to the no. sealed on one complete rotation of the sealing roller surface. |
7.8 IN-PROCESS CHECKS DURING SECONDARY PACKAGING IN TABLETS AND CAPSULES
| Parameters | Details to be checked |
| Batch details on carton/ cache cover | Check the batch details as per BPR and also observe for
legibility of letters, missing of letters or smudging of ink etc. |
| Proper gluing of side seam/bottom lock of
carton/catch cover |
The sealing of side seam and lock bottom flaps of carton / cache
cover should be intact and shall not show any opening. |
| Number of strips in one carton / cache cover as per
required pack profile |
Check each carton or catch cover for the total number of strips
and verify the results with pack profile mentioned in BPR. |
| Number of unit cartons in one outer shipper (Corrugated box) as per required pack size | Count the number of unit cartons in one outer shipper and
verify with the pack size mentioned in the BPR and outer shipper. |
| Presence of package insert / Patient information leaflets | Before final closing of carton / unit carton, ensure the presence of package insert in each carton / unit carton, wherever
applicable. |
| Proper insertion of tuck-in flaps | Check whether the tuck-in flaps of the cartons are properly
inserted and locked with the supporting flaps or not. |
7.9 IN-PROCESS TERTIARY PACKAGING CHECKS
| Parameters | Details to be checked |
| No. of bottles/cartons/shrink packed units in one
shipper (corrugated box). |
Count the no. of bottles/cartons/shrink packed units in one
shipper. |
| Overprinting on corrugated boxes | Check the overprinting details on the shipper |
| Pasting of BOPP tape | Check the pasting of BOPP tape on corrugated box for peeling-
off of tape or opening of seal etc. |
| Gross weight of shipper | Check and record for gross weight of shipper |
| Loose Shipper | Check the loose shipper for number of bottles/cartons/Shrink packed units. The label of loose shipper shall be signed by production and cross verified by QA for loose quantity. The
gross weight of the loose shipper shall be written in the shipper. |
8.0 REVISION HISTORY
Version No. Effective Date Details of revision: