ORIGINAL Confidential

SUMMARY OF 3 BATCHES
OSTELOX® SUPPOSITORIA
VALIDATION REPORT

Document No. : VAL-PV/PVR/MB/511-B1, B2, B3 Batch #1 : SE9925

Batch #2 : SJ9943
Batch #3 : SM9963
Revision No. : 00
Date : 30 DECEMBER 2016
Product : OSTELOX® SUPPOSITORY (Batch Size : 8.5 Kg, @1.7 g)

Code : 19003
MS No. : PRO-SS/BRC/MB/089-SB Rev. 00
PRO-LI/BRC/MB/090-SB Rev. 00
TS No. : SP-OJ-658, Rev.01
Site : PT. CAPRIFARMINDO LABORATORIES
(Pharmaceutical Plant)
Jl. Industri Cimareme No. 8 Block H Kab. Bandung Bara
Indonesia

Prepared by:
Function Name/Title Signature Date
R. Dery Pramudya Firdaus /
Production
Production Manager
Novi Indra Fatmawati /
Validation
Process Validation Engineer

Reviewed & Approved by:

Function Name/Title Signature Date
Arif Agus Setiawan /
Validation
Validation Manager
Herwanto /
R&D
Reviewed R&D Corp. General Manager
Quality Rahmi Budi A. /
Control QC Manager
Plant Khairudin /
Manager Plant Manager
QA Lutfi Febrina /
Manager QA Manager
Approved
Head of Sumardi /
Quality Head of Quality

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SUMMARY

Process validation has been performed concurrently to 3 (three) consecutive batches of

OSTELOX® Suppository, those are batch number SE9925, SJ9943, and SM9963. The aim of this
validation is to to ensure that the production process of Ostelox® Suppository based in the batch
record for 8.5 Kg for 5,000 Suppository @1.7 g batch size will produce high degree quality
product consistently. Revalidation is conducted due to change the supplier of Meloxicam as an
Active Pharmaceutical Ingredient from Zhejiang Excel, China (A) to be Harika Drugs Private
Limited, India (B).
The details of the results are shown in the below section.
Starting Materials

Formula
Batch Size: 8.6 Kg for 5,000 suppositories @1.7 g
Meloxicam 0.075 kg
Suppocire BM Pastilles 8.425 kg

A. Mixing Process
All critical parameters and testing result in mixing process comply with the acceptance
criteria.

The result of sampling on mixing process could be seen at table below :

A.1 Appearance
Parameter
No. Batch Acceptance Criteria Result Pass/Fail
Tested
SE9925 Appearance
- Color Yellow Yellow Pass
- Odor Odorless Odorless
SJ9943 Appearance
- Color Yellow Yellow Pass
- Odor Odorless Odorless
SM9963 Appearance
- Color Yellow Yellow Pass
- Odor Odorless Odorless

Based on the above results of the process validation result of the 3 validation batches for the
appearance parameter test is meet specification.

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A.2 Identification

No. Batch Sample Acceptance Criteria Result Pass/Fail

SE9925 Top 1 Positive Pass
Top 2 Positive Pass
Top 3 Positive Pass
Top 4 Positive Pass
Middle 1 Positive Positive Pass
Middle 2 Positive Pass
Middle 3 Positive Pass
Middle 4 Positive Pass
Middle 5 Positive Pass
Bottom Positive Pass
SJ9943 Top 1 Positive Pass
Top 2 Positive Pass
Top 3 Positive Pass
Top 4 Positive Pass
Middle 1 Positive Positive Pass
Middle 2 Positive Pass
Middle 3 Positive Pass
Middle 4 Positive Pass
Middle 5 Positive Pass
Bottom Positive Pass
SM9963 Top 1 Positive Pass
Top 2 Positive Pass
Top 3 Positive Pass
Top 4 Positive Pass
Middle 1 Positive Positive Pass
Middle 2 Positive Pass
Middle 3 Positive Pass
Middle 4 Positive Pass
Middle 5 Positive Pass
Bottom Positive Pass

Based on the above results of the process validation result of the 3 validation batches for the
identification parameter test is meet specification.

A.3 Assay of Paracetamol

Acceptance RSD (<
No. Batch Sample Result Pass/Fail
Criteria 5%)
SE9925 Top 1 95.0 % - 110.0 % 107.8 % 2.96 Pass

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Acceptance RSD (<

No. Batch Sample Result Pass/Fail
Criteria 5%)
Top 2 101.4 % Pass
Top 3 98.8 % Pass
Top 4 101.3 % Pass
Middle 1 101.1 % Pass
Middle 2 106.9 % Pass
Middle 3 104.5 % Pass
Middle 4 103.3 % Pass
Middle 5 107.5 % Pass
Bottom 102.8 % Pass
SJ9943 Top 1 99.9 % Pass
Top 2 95.5 % Pass
Top 3 101.5 % Pass
Top 4 96.5 % Pass
Middle 1 95.0 % - 110.0 % 100.5 % Pass
2.02
Middle 2 99.1 % Pass
Middle 3 97.8 % Pass
Middle 4 100.9 % Pass
Middle 5 97.3 % Pass
Bottom 98.2 % Pass
SM9963 Top 1 101.2 % Pass
Top 2 101.3 % Pass
Top 3 96.3 % Pass
Top 4 97.5 % Pass
Middle 1 95.0 % - 110.0 % 97.5 % Pass
2.33
Middle 2 98.5 % Pass
Middle 3 97.8 % Pass
Middle 4 98.7 % Pass
Middle 5 102.4 % Pass
Bottom 100.4 % Pass
Based on the above results of the process validation result of the 3 validation batches for the
Assay parameter test is meet specification.
Statistically evaluation for Assay :
Anova: Single
Factor
SUMMARY
Groups Count Sum Average Variance
SE9925 10 10.354 1.0354 0.000941
SJ9943 10 9.872 0.9872 0.000396
SM9963 10 9.916 0.9916 0.000411
ANOVA
Source of
Variation SS df MS F P-value F crit

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Between Groups 0.014203 2 0.007102 12.19422 0.000169 3.354131

Within Groups 0.015724 27 0.000582

Total 0.029928 29

This section shows the ANOVA table as in the material one way ANOVA . which needs to be
seen in this section is the P value. P value smaller than 0.05, therefore the decision H0 was
rejected, which means there is difference in the average of each group, but it doesn’t impact
the product considering the assay for each sampling point meet the specification which is
within 95.0 % - 110.0 %, and also the RSD result for each batches are smaller than 5 %.

B. Filling Process
All of the critical parameters and testing results comply with the acceptance criteria.
The data on filling process can be seen at table below :
B.1 Appearance and Disintegration
Parameter
No. Batch Acceptance
Result Pass/Fail
Tested Criteria
SE9925 Form Torpedo Torpedo Pass
Color Yellow Yellow Pass
Odor Odorless Odorless Pass
Disintegration Time
Beginning 12 min. 28 sec
< 30 minutes Pass
Middle 12 min. 57 sec.
End 13 min. 10 sec.
SJ9943 Form Torpedo Torpedo Pass
Color Yellow Yellow Pass
Odor Odorless Odorless Pass
Disintegration Time
Beginning 05 min. 43 sec
< 30 minutes Pass
Middle 04 min. 58 sec.
End 06 min. 12 sec.
SM9963 Form Torpedo Torpedo Pass
Color Yellow Yellow Pass
SM9963 Odor Odorless Odorless Pass
Disintegration Time
Beginning 15 min. 15 sec
< 30 minutes Pass
Middle 15 min. 40 sec.
End 16 min. 06 sec.

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Based on the above results of the process validation result of the 3 validation batches for the
appearance parameter test and disintegration is meet specification.

B.2 Diameter, Weight, PCI Weight, and Length

No. Parameter Pass/

Batch Acceptance Criteria Result
Tested Fail
SE9925 Diameter
Beginning - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.885 – 0.925 cm
( xx = 0.912 cm)
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.068 – 1.122 cm
( xx = 1.104 cm)

Middle - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.903 – 0.920 cm

( xx = 0.913 cm) Pass
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.071 – 1.098 cm
( xx = 1.087 cm)

End - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.901 – 0.914 cm

( xx = 0.907 cm)
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.068 – 1.098 cm
( xx = 1.092 cm)
Weight
Beginning 1.7 g + 5% 1.711 g
Pass
Middle (1.615 g – 1.785 g) 1.711 g
End 1.712 g
Length
Beginning - 3.1 + 5% ; 2.945– 3.255 cm 2.703 – 2.784 cm
(xx = 2.745)
See
Middle - 3.1 + 5% ; 2.945– 3.255 cm 2.689 – 2.717 cm
discussion
(xx = 2.738)
End - 3.1 + 5% ; 2.945– 3.255 cm 2.702 – 2.801 cm
(xx = 2.745)
PCI of
> 1.33 4.55 Pass
Weight

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No. Parameter Pass/

Batch Acceptance Criteria Result
Tested Fail
SJ9943 Diameter
Beginning - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.884 – 0.898 cm
( xx = 0.893 cm)
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.085 – 1.099 cm
( xx = 1.089 cm)

Middle - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.884 – 0.899 cm

( xx = 0.892 cm) Pass
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.081 – 1.090 cm
( xx = 1.085 cm)

End - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.890 – 0.918 cm

( xx = 0.904 cm)
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.092 – 1.099 cm
( xx = 1.096 cm)
Weight
Beginning 1.7 g + 5% 1.720 g
Pass
Middle (1.615 g – 1.785 g) 1.708 g
End 1.706 g
Length
Beginning - 3.1 + 5% ; 2.945– 3.255 cm 2.728 – 2.779 cm
(xx = 2.752)
See
Middle - 3.1 + 5% ; 2.945– 3.255 cm 2.722 – 2.788 cm
discussion
(xx = 2.756)
End - 3.1 + 5% ; 2.945– 3.255 cm 2.714 – 2.775 cm
(xx = 2.742)
PCI of
> 1.33 3.10 Pass
Weight
SM9963 Diameter
Beginning - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.900 – 0.925 cm
( xx = 0.912 cm)
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.07 – 1.099 cm
( xx = 1.082 cm)

Middle - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.9.02 – 0.9.15 cm

( xx = 0.909 cm) Pass
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.080 – 1.086 cm
( xx = 1.085 cm)

End - 0.9 + 3% ; 0.873 - 0.927 cm (lip) 0.910 – 0.920 cm

( xx = 0.915 cm)
- 1.1 + 3% ; 1.067-1.133 cm (neck) 1.082 – 1.095 cm
( xx = 1.088 cm)
Weight
Beginning 1.7 g + 5% 1.720 g
Pass
Middle (1.615 g – 1.785 g) 1.705 g
End 1.711 g

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No. Parameter Pass/

Batch Acceptance Criteria Result
Tested Fail
SM9963 Length
Beginning - 3.1 + 5% ; 2.945– 3.255 cm 2.609 – 2.690 cm
(xx = 2.660)
See
Middle - 3.1 + 5% ; 2.945– 3.255 cm 2.604 – 2.670 cm
discussion
(xx = 2.646)
End - 3.1 + 5% ; 2.945– 3.255 cm 2.633 – 2.690 cm
(xx = 2.667)
PCI of
> 1.33 3.48 Pass
Weight

Based on the above results of the process validation result of the 3 validation batches for the
diameter, weight, pci weight parameter test is meet specification. Based on those data, the
examination results “Length” of suppositories did not meet the specifications, the data was
in accordance with the trend of the examination results in Ostelox ® Suppositoria products,
but the results of Weight, Assay and Uniformity of Dosage Unit met the requirements, based
on those conditions (Data Validation and IPC) is recommended to change the length
specification of SPOJ to be "as info" of 2.7 ±5%; 2.565- 2.835 cm

B.3 Identification

No. Batch Sample Acceptance

Result Pass/Fail
Criteria

SE9925 Beginning Positive Pass

Middle Positive Positive Pass

End Positive Pass

SJ9943 Beginning Positive Pass

Middle Positive Positive Pass

End Positive Pass

SM9963 Beginning Positive Pass

Middle Positive Positive Pass

End Positive Pass

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Based on the above results of the process validation result of the 3 validation batches for the
identification parameter test is meet specification.

B.4 Assay of Meloxicam

No. Batch Sample Acceptance Result RSD Pass/Fail

Criteria (< 5%)
Beginning 105.5 % Pass
Middle 95.0 – 110.0 % 103.2 % 3.87 Pass
SE9925
End 97.8 % Pass
Beginning 98.7 % Pass
SJ9943 Middle 95.0 – 110.0 % 95.6 % 1.79 Pass
End 95.8 % Pass
Beginning 100.1 % Pass
Middle 95.0 – 110.0 % 97.1 % 1.81 Pass
SM9963
End 100.3 % Pass

Based on the above results of the process validation result of the 3 validation batches for the
Assay parameter test is meet specification.

Statistically evaluation for Assay :

SUMMARY
Groups Count Sum Average Variance
SE9925 3 3.065 1.021667 0.001562
SJ9943 3 2.901 0.967 0.000301
SM9963 3 2.975 0.991667 0.000321

ANOVA
Source of Variation SS df MS F P-value F crit
Between Groups 0.004497 2 0.002248 3.08758 0.119682 5.143253
Within Groups 0.004369 6 0.000728

Total 0.008866 8

This section shows the ANOVA table as in the material one way ANOVA . which needs to be
seen in this section is the P value. P value greater than 0.05, the decision received H0 means
there is no difference in the average of each group

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B.5 Leakage test

No. Batch Acceptance

Result Pass/Fail
Criteria
SE9925 Pass
No Leakage
SJ9943 No Leakage
No Leakage Pass
SM9963 Pass
No Leakage

Based on the above results of the process validation result of the 3 validation batches for
the leakage parameter test is meet specification

The PCI (Process Capability Index) result of filling volume is meet the defined limit (actual PCI
of batch SE9925 is 4.55, SJ9943 is 3.10, and SM9963 is 3.48, acceptance criteria ≥ 1.33).

weight variation chart of SE9925

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weight variation chart of SJ9943

weight variation chart of SM9963

Based on the results of the process validation result of the 3 validation batches, the process
validation is PASS.

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