Standard Operating Procedure

Title: In-Process Control & Checks

Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 1 of 8 Pakistan.

1. OBJECTIVE
The purpose of this procedure is to establish a procedure for in-process checks performed
during production in order to monitor the process and ensure that the product conforms to its
specifications.

2. SCOPE
This procedure covers the In-Process checks of the manufacturing and packaging of
pharmaceutical products at Aspin Pharma (Pvt.) Ltd.

3. RESPONSIBILITIES
S. No. Action Responsibility
Production
Officer/QA Officer/
3.1. To perform and verify the in-process checks
Technical officer/
Designee
Manager QA(C&E)
To ensure that in-process checks procedure is properly implemented /Sr. Manager
3.2.
and compliance with the SOP. Production /
Designee

4. GENERAL REQUIREMENTS
4.1. Production Officer and QA Officer will ensure that all in process documents must be part
of batch document.
4.2. All in process documents must be retained along with batch document for a period of
expiry plus one year.
4.3. First In process check by Production Officer and QA officer or designee will be part of Line
clearance.
4.4. Viasala devices are installed with the help of high quality magnet for online monitoring the
Temperature and Humidity in GMP areas.
4.5. At the time of line clearance and in-process, QA officer and production officer will be verified
the temperature and humidity by wall mounted Vaisala devices (Where applicable).
4.6. During in-process monitoring, any non-compliance observed will be dealt by the SOP for In-
process Monitoring Observation ref. # QA/SOP/IPMO/243.

4.7. Frequency:
Process By Operator By Production Supervisor By QA
Over Printing At least one time At least one time in 2 hours. At least one time in 2
in 1 hour. hours.
Filling At least one time At least one time in 2 hours. At least one time in 2
in 1 hour. hours.
Weight of 10 tablets / At least one time At least one time in 2 hours At least one time in 2
capsules in 15 minutes hours.
 Standard Operating Procedure
Title: In-Process Control & Checks
Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 2 of 8 Pakistan.

Weight Variation of At least one time At least one time in 2 hours. At least one time in 2
tablets / capsules in 1 hour. hours.
Hardness At least one time At least one time in 2 hours. At least one time in 2
in 1 hour. hours.

Start of Batch, After

Every Break, and

Thickness At least one time At least one time in 2 hours. At least one time in 2
in 1 hour. hours.
Disintegration time One time in a day One time in a day One time in a day
Friability One time in a day One time in a day One time in a day
Leak Test (Blistering) Start of batch / Start of batch / Start of batch /
Start of shift / start Start of shift / start of new Start of shift / start of new
of new roll, any roll, any breakdown and roll, any breakdown and
breakdown and once in every two hours. once in every two hours.
once in every two
hours.
Blistering At least one time At least one time in 2 hours. At least one time in 2
in 1 hour. hours.
Final Packaging N/A At least one time in 2 hours. At least one time in 2
hours.

4.8. Sampling
Steps No. of samples

Printing Five samples per check.

Syrup / Drops/
Suspensions/ tablets One stroke per check.
Filling
Cream / gel Filling and
5 Tubes per check.
crimping & embossing
Compression 1. Weight of 10 tablets per check
2. Individual weight of 20 tablets per check.
3. Hardness of 05 tablets per check.
4. Friability
4.1. For tablets with a unit weight equal to or less than 650 mg, take
sample equivalent or near to 6.5 g.
4.2. For tablets with a unit weight of more than 650 mg, take a sample of
10 whole tablets.
5. Disintegration time of 6 tablets per check.
 Standard Operating Procedure
Title: In-Process Control & Checks
Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 3 of 8 Pakistan.

6. Thickness of 5 tablets per check.

Encapsulation 1. Weight of 10 capsules per check.
2. Individual weight of 20 capsules per check.
1. Average weight of 10 3. Color of body & cap of 5 capsules per check.
capsules per check. 4. Disintegration time of 6 capsules per check
Coating 1. Individual weight of 20 Tablets per check after coating.
1. For Leak test one full stroke with product.
Blistering
2. For blistering five samples per check randomly.
Final Packaging
Five samples per check randomly.
- Minimum 3 packs per
check randomly.

4.9. Defects and their Classification

Defects Type of Classification
Defects
4.8.1 Printing
Wrong/mixed display carton Critical When one or more bottle labels/display
Wrong Batch No. Critical Wrong batch No. Printed on labels/cartons.
Critical Wrong Mfg./Expiry date printed on
Wrong Mfg./Exp. date
Major One or more labels/cartons observed
Major Printing partially cut-off and not readable
Printing cut-off
Minor Letter No. Inverted/digits missing or double
4.8.2 Filling (Cream/Gel/liquid)
Mixed/wrong Al tube Critical One or more wrong tube observed.
One or more bottle/tube observed without product in
Empty bottle/tube. Critical final packaging (Final release)/on line
Pin holes in Al tube. Critical One or more tubes observed with pin holes
Critical Cut mark observed on cap or capping
Defective capping.
Major Cut mark observed on cap but no leakage
Broken notches Cap observed with broken notches.
Major

One or more bottles/tubes observed damaged from

Critical
Damaged bottle/tube final packaging and result leakage.
Major One or more bottles/tubes observed
Dented tubes Minor If dented tubes observed on line
One or more Al tubes observed without printing of
Unprinted tube Critical
text
One or more tubes were observed with wrong batch
Improper/poor Batch No. Critical
No. embossing/expiry date.
embossing/Expiry date
Major Batch No. embossed not clearly readable
Improper crimping Critical One or more tubes were observed with improper
crimping result leakage
 Standard Operating Procedure
Title: In-Process Control & Checks
Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 4 of 8 Pakistan.

Major One or more tubes were observed with improper

crimping result no leakage
4.8.3 Encapsulation
Empty capsules One or more capsules observed empty
Critical
Wrong or mixed Critical One or more different capsules observed
Damaged capsules observed from final
Damaged capsules Major
packaging/online
Powder dusting observed on capsules or in blister
Major
during final packaging and on line.
Powder dusting on capsules
Powder dusting observed on capsules during
Minor
capsulation
Dented capsules observed from final Packaging and
Major
on line
Dented capsules
Dented capsules observed during capsulation.
Minor
4.8.4 Compression
Capping Major Capping observed during compression
Friability Friability observed out of specified limit
Major
Chipping Major Chipping observed during compression
Hardness Major Hardness observed out of specified limit.
Disintegration time Critical Disintegration time observed out of specified limit
Wrong punches used Critical Wrong punches used during compression
4.8.5 Blister Packaging
Leakage Major Leakage observed in one/more strip on line
Damaged capsules / tablets Major Damaged tablets/capsules observed on line
Mixed/wrong Batch No. One or more strips observed with wrong Embossing
Critical
or Expiry date embossing Batch No. /Expiry date.
Wrong or mixed Al. foil Critical Al foil used of different product
Major Text printing cut-off such as B. No. Reg. No., Mfg.
date and product name etc. OR any letter of
embossing is missing (not readable)
Printing text cut-off
No., Mfg. date
and product
name etc.
Text printing cut-off such as
B.No., Reg.

(not readable)
Strip observed on line without product or short more
Empty strip/short product Major
than one tablet or capsule from blister packaging
4.8.6 Final Packaging
Wrong/mixed product Critical Mixed up or wrong product or packaging material
 Standard Operating Procedure
Title: In-Process Control & Checks
Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 5 of 8 Pakistan.

observed from line/packaging.

Critical

Mixed up or wrong product or

packaging

One or more strips/bottles observed empty from final

Empty strip/bottles Critical
packaging/on line.
Wrong batch # and exp. Date embossed on blisters
Embossing of blister & Tubes Critical
and tubes.
Without Batch#, Exp. Date, Bottle label/display carton observed without Batch#,
Mfg. date, MRP, and GTIN# Exp. Date, Mfg. date, MRP, and GTIN#(display
Major
(display cartons) cartons) on final packaging.

Outer carton observed without signature of

Without signature Minor
authorized worker.
Strip observed on line without product or short more
Short product critical
than one tablet or capsule from blister packaging.
Critical One or more wrong insert observed,
Major If insert observed missing in complete batch.
One or two insert observed missing in complete
Missing/incorrect insert
batch.
Minor

Major Text partially cut of/poor (not readable)

Text of display carton or label
Minor Text partially cut of/poor (but readable)
is not eligible
Major Wrong quantity on PSTN.
One or more than one unit found short in shipper
Short product in shipper carton Major
carton.
5. PROCEDURE:
S. No. Action Responsibility
Printing of Cartons: check the following Production
Text of display cartons Bar code information, GTIN No., Batch No., Officer/QA Officer/
5.1.
Manufacturing date, expiry date, product name, price and Art work Technical officer/
codes. Designee
Printing of Labels: check the following Production
Officer/QA Officer/
5.2. Text of labels, Batch No., Manufacturing date, expiry date, product
Technical officer/
name, price and Art work codes. Designee
Production
Printing of Shipper Labels: check the following Officer/QA Officer/
5.3.
Text of Shipper labels, Batch No., expiry date, product name. Technical officer/
Designee
5.4. Filling of Liquid: check the following Production
 Standard Operating Procedure
Title: In-Process Control & Checks
Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 6 of 8 Pakistan.

S. No. Action Responsibility

Officer/QA Officer/
Volume variation, sealing Quality of Caps, broken notches. Technical officer/
Designee
Filling of Cream / Gel: check the following Production
5.5. Weight variation, Pin holes, dented tube, proper embossing (B. No. & Officer/QA Officer/
Technical officer/
Exp. date), crimping quality & appropriate folding of Aluminium Tube. Designee
Compression: check the following Production
Officer/QA Officer/
5.6. Physical appearance, marking, weight variation, Hardness, Friability,
Technical officer/
Disintegration time, Thickness. Designee
Encapsulation: check the following Production
5.7. Physical appearance (size of capsules and colour of capsules), locking Officer/QA Officer/
Technical officer/
(closing of capsules), weight variation and disintegration time. Designee
Production
Coating: check the following Officer/QA Officer/
5.8.
Physical appearance, weight variation Technical officer/
Designee
Blistering: check the following Production
Text of strip, identification of P.V.C Standard, or P.V.C Tri-Star / Officer/QA Officer/
5.9. Triplex, Aluminium foil, product, proper embossing (B. No. & Exp. Technical officer/
Designee
date) on strips (one stroke), vacuum test, sealing and forming
temperature, pocket shape and quantity of tablets in one blister.
Final Packaging: check the following Production
Text of display cartons, bottle labels and shipping labels, batch no., Officer/QA Officer/
expiry date, manufacturing date, price, leaflets, measuring cups, Technical officer/
5.10.
spoon, applicators etc. Quality of display cartons and shipper cartons, Designee
quantity of product in display carton and quantity of packs in shipper
carton and shipping label, weight of unit cartons (where applicable)
and weight of shipper carton.

6. DEFINITIONS
 Standard Operating Procedure
Title: In-Process Control & Checks
Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 7 of 8 Pakistan.

S. No. Term/word/statement Meaning/Description

A defect that is likely to result in producing an unsafe condition or
contravene mandatory regulation. In our normal practice, no
6.1 Critical Defect
Critical Defect is accepted; any of this kind of defect found will be
subjected to an automatic rejection of inspection result.
A defect, which will cause an observable product failure or
6.2 Major Defect
departure from requirements.
6.3 Minor Defect A defect that will not cause a failure in execution of the product.
6.4 PSTN Pack Stock Transfer Note

7. REFERENCES USED:
S. No. Description
7.1. BS 6001 Part I 1991 Simple Normal Sampling Plan Level II
7.2. FDA 21cfr Part 211 - Current Good Manufacturing Practice For Finished Pharmaceuticals
Subpart F-Production and Process Controls sec.211.100 sampling & testing of in-process
and drug products.
7.3. WHO guidelines Annexure 3 point16.6,16.32,
8. REFERRED DOCUMENTS:
S. No. Document No. Description
8.1. QA/SOP/PLC/161 SOP for line clearance
8.2. QA/SOP/IPMO/243 SOP for In-process Monitoring Observation

9. FORMATS & FORMS:

S. No. Document No. Description
9.1 QA/SOP/IPC/068-A In-process sheet for compression
9.2 QA/SOP/IPC/068-B In-process sheet for encapsulation
9.3 QA/SOP/IPC/068-C In-process sheet for tubes filling
9.4 QA/SOP/IPC/068-D In-process sheet for blistering
9.5 QA/SOP/IPC/068-E In-process sheet for liquid filling
9.6 QA/SOP/IPC/068-F In-process sheet for over printing
9.7 QA/SOP/IPC/068-G In-process sheet for packaging
9.8 QA/SOP/IPC/068-H In-process sheet for Weighing
9.9 QA/SOP/IPC/068-I In-process sheet for Coating

10. HISTORY
Versio Effective
Issue Date Description of Change
n No. Date
01 N/A 17.05.2019 This is the 1st Version of SOP on new format as per
Management of documentation control (QA/SOP/MDC/001).
 Standard Operating Procedure
Title: In-Process Control & Checks
Document No. Version No. Supersede Date
QA/SOP/IPC/068 04 30.11.2021 Aspin Pharma (Pvt.) Ltd.
Preparation Date Review Date Page No. Plot No. 10 & 25, Sector
20, K.I.A, Karachi-
28.02.2023 27.02.2026 Page 8 of 8 Pakistan.

However, before this new version, SOP for In-Process Control

& Checks was exist on old format via Document No.
SOP.QO.0140. Ver 2.0, that stands retired.
SOP revised to improve in process check for crimping of
02 N/A 20.09.2019
aluminium tubes.
SOP revised due to change in frequency of in process checks
03 as well as addition of in-process sheets to be used for different
25.11.2021 30.11.2021
processes in BMR and BPR as per the CC No. CC.218.2021.
SOP revised as per Change Control No. CC.120.2022 and also
as per risk assessment No.QR.018.22 to add the verification
04
check of Temperature & Humidity through the Viasala devices
in GMP area.

11. DISTRIBUTION LIST

Copy No. Department
Original QA Documentation Control
1 Quality Assurance (C&E)
2 Manufacturing Department
3 Packaging Department

END OF THE DOCUMENT