Process Validation Protocol For Ketofast 10 Tablet

Veritas Pharmaceuticals limited Process Validation
Muradpur,Vannara,Mouchak,Gazipur VPL-PVP-007
Rev No.: 00
VERITAS PHARMACEUTICALS LTD

Muradpur, Vannara, Mouchak, Kaliakoir, Gazipur
Document Title: Process Validation Protocol of Ketofast 10

Tablet
Document Number : VPL-PVP-007, Revision - 00
Document Type : Concurrent Validation
Prepared by Checked by Agreed by Approved by Date
Signature
Name Md. Shafayat Hossain Md. Tarikul Islam Bossunia H. M. Jahid Murad Md. Moniruzzaman
Sr. Executive, Product Quality Assurance
Designation Asst. Manager, QC Manager, Production
Development Manager
Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 1 of 26

Rev No.: 00
TABLE OF CONTENT
01 Introduction 3
02 Purpose 3
03 Scope 3
04 Validation team 3
05 Qualification and training of personnel 3
06 Calibration and qualification status of equipment 4
07 Batch details of validation batches 4
08 Qualification of starting materials 4
09 Details of reference / working standards 5
10 Validation methodology 5
11 Manufacturing procedure details 5
A Unit formula 5
B (i) Manufacturing formula 5
B (ii) List of Coating material 6
B (iii) List of packaging materials 6
C Process Description 6-7
D Manufacturing flow chart 8
12 Special precaution 8
13 Process parameters for IPC test 8
14 Analytical Test Methods 8
15 Sampling plan 9
16 Acceptance criteria & finish product specification 10
17 Critical process parameters and justification 11-13
18 Analysis of sample 14-18
19 Summary of test result of individual batch 19-20
20 Summary format of three validation batches 20-22
21 Reference documents 23
22 Yield Summary 23
23 Deviation reporting 23
24 Revalidation 23
25 Review of results and reporting 23
26 Final summary report 23
27 Compilation of control data and records 23
28 Batch Analysis report 23
29 Final Approval 24
30 Appendices 24
31 Revision History 24
1.0 Introduction
This protocol includes the process validation activities for the manufacture of Ketofast 10mg
Tablet (Batch size: 41.250 Kg, 2, 75,000 pcs). These validation activities will be carried out on
three successive batches. The process is validated when three successful batches of this

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product will made by same procedure and can meet the acceptance criteria stated in this
protocol.
0.0 Purpose
The objective of the Performance Qualification for concurrent Validation is to verify that the
manufacturing equipment, raw material and the manufacturing & coating process for Ketofast
10 mg tablet specified in SPEC/PK 001/GR/00, SPEC/PK 001/IP/01, SPEC/PK 001/CT/01 &
SPEC/PK 001/FP/01 produces a tablet product of the consistent strength, friability, weight,
hardness, dissolution, thickness, disintegration and LOD/moisture content.
1.0 Scope
This protocol is valid for Performance Qualification of Concurrent Validation for Ketofast 10mg
tablet manufacturing facility of VPL, Gazipur.
2.0 Validation Team

The exercise will be carried out by participation of the members from QA, QC, Production,
Engineering and Product Development. The team is not exclusive and others may become
part of the validation if it is considered necessary. During validation exercise any changes will
be controlled by the change control.
Validation team & responsibilities
Department Designation Responsibilities

To coordinate the entire validation process by scheduling
meetings and discussions with production, quality control and
Product Executive/Sr. quality assurance. Preparation of preliminary validation
Development Executive protocol, master formula record, monitoring the process,
compiling and analyzing data and test results and preparing
the final report. To review the preliminary validation documents.
Executive/Asst. To participate in performing the validation steps during
Production
Manager manufacturing processes. To assist in collection of data.
To coordinate the entire validation process by scheduling
meetings and discussions with the team.
Quality Preparation of validation protocol, monitoring the process,
Executive
Assurance compiling and analyzing data and test results and preparing the
final report. To review of validation documents. Collect sample at
different stages.
Quality Executive/Sr.
To test and report the test results at different stages.
Control Executive
Quality Will ensure that all tests are performed at different stages. To
Head
Control check results.
To ensure product is manufactured following protocol and overall
Production Manager
co-operation in validation activities
To approve the process validation protocol and report.
Quality
Manager To review of validation documents.
Assurance
To approve the process.
5.0 Qualification and training of personnel

Personnel engaged in the Validation project must have adequate qualification and should be
trained in the basic principles of validation and should be thoroughly briefed about the
manufacturing process Ketofast 10mg tablet and the detailed methodology to be adopted for
the Performance Qualification of the process.
A list of the personnel with the qualification and training details should be prepared as per the
following format:
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Name Designation Department Signature of Trainee Signature of Trainer
6.0 Calibration and qualification status of equipment and utility system

The calibration and qualification status of the following equipments used in the Performance
Qualification of process Ketofast 10 mg Tablet shall be checked and listed in the following
format.
Batch No. Batch Size:
Identification Last qualification
Equipment Name Ref. Doc. Remarks
No. /Calibration date
7.0 Batch details of validation batches
A minimum three consecutive batches shall be planned for the validation project. The batch
details of validation batches shall be planned well in advance. If three batches are not
available, concurrent validation will be carried out.
The batch size of these batches shall be maintained uniform and no recovery from previous
batches shall be added in these batches
8.0 Qualification of starting materials

All the raw materials proposed to be used for the manufacture of validation batches shall have
the following qualification.
Name of the materials QC Ref. No. Release status Remarks
9.0 Details of reference / working standards

Sl. Exp. Date/
Name Source Ref. No. Strength
No. Retest test
01
02
03
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04
05
10.0 VALIDATION METHODOLOGY
10.1 The validation will be performed on three consecutive production scale batches of the same
batch size following the established manufacturing process described in this validation
protocol as well as Batch Manufacturing Record (BMR). If three batches are not available,
concurrent validation will be carried out.
10.2 It shall be carried out at optimum values within the acceptable ranges of critical process control
parameter. All critical process parameter will be monitored and documented for review.
10.3 Sampling shall be done following sampling plan given in this protocol as per PQ.
10.4 Finished product sampling and testing shall be carried out as per the established sampling
procedure and testing procedure respectively.
10.5 During execution of the validation protocol batch record will be completed. Results of all critical
process control parameter and batch information will be recorded in Critical Process Parameter
Manufacturing Ranges.
10.6 Process validation shall be considered successfully when three (3) successful batches of
Ketofast 10 mg tablet have been manufactured using the critical parameter in section 16 and
finished products meets its specification for three batches.
11.0 Manufacturing procedure details
A) Unit formula:
Ingredients Code No. mg/Tab
Ketorolac Tromethamine 1111001 10.000
Microcrystalline Cellulose (Avicel PH 102) 1113005 130.392
Sodium Starch Glycolate 1119001 7.502
Colloidal Silicon Dioxide (Aerosil 200) 1103001 1.124
Magnesium Stearate 1113002 0.750
Green Lake 1103001 0.233
B) (i) Manufacturing formula

Batch
Batch size 41.25 Kg 275000 Standard Qty B/N.:
Qty
(Kg/Batch)
Ingredients Code No. Actual Qty.
Ketorolac Tromethamine 1111001 2.750*
Microcrystalline Cellulose (Avicel PH 102) 1113005 35.858*
Sodium Starch Glycolate 1119001 2.063
Colloidal Silicon Dioxide (Aerosil 200) 1103001 0.309
Magnesium Stearate 1113002 0.206
Green Lake 1103001 0.064
*The quantity will be calculated based on potency.
B) (ii) List of Coating materials

Code No. Description of Materials Standard Qty (Kg) Actual Qty
1108001 Hydroxy propyl Methyl Cellulose (15cps) 2.550
1113006 Methylene Chloride 25.500
1113007 Methanol 25.500
1116003 Polyethylene Glycol (PEG-6000) 0.284
1120001 Titanium Dioxide 0.070
1120002 Purified Talc 0.378
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1117003 Green Lake 0.005
B) (iii) List of packaging materials

Code No. Description of Materials Standard Qty (Kg) Actual Qty
120002 Printed Alu Foil for Ketofast 10 Tablet
120010 Alu Bottom foil 228 mm
030005 Leaflet for Ketofast 10 Tablet
040005 Inner Carton for Ketofast 10 Tablet (2X10s)
110001 Hollogram Sticker
060005 Master Carton Size # 1
070026 Master Carton Label for Ketofast 10 Tablet
100001 Gum Tape 2"
100002 Glue
C) PROCESS DESCRIPTION
1. Dispensing order
a. Ketorolac Tromethamine
b. Microcrystalline Cellulose (Avicel PH 102)
c. Sodium Starch Glycolate
d. Colloidal Silicon Dioxide (Aerosil 200)
e. Magnesium Stearate
f. Green lake
2. Granulation
i) Sieving: Sieve the following materials through mesh # 20/60
Ketorolac Tromethamine
Microcrystalline Cellulose ( Avicel PH 102)
Sodium starch Glycolate
Green Lake (use mesh #60)
ii) Dry Mixing: Take the sieved materials of step I the Pillar Bin Blender & mix for 30
minutes
iii) Lubrication & Blending: Sieve & take the following materials along with the dried granules
of step II & Mix for 10 minutes in the Pillar bin Blender. Measure LOD/Moisture content, which
will be within (2.5 3.5) %. If necessary, dry further.
Colloidal Silicon Dioxide ( Aerosil-200)
Magnesium Stearate
iv) Discharge: Discharge the materials into double polythene bags with silica gel
between the bags placed in a plastic drum. Close it tightly & mark the drum with
Product Name, Batch No, Date, Gross weight, Tare along with signature of the
operator.
v) Sampling and Testing: Carryout sampling and testing as per sampling plan 15.0 &
18.0.
3. Compression
Granules are compressed in Cadmac 45 Punch machine by maintaining following specification
mentioned:
SPECIFICATIONS
Machine : B-type Press: Cadmac 45 Punch
Punch set : Round
Upper punch : Engraved with V
Lower punch : With break line
Average weight : 142.50.0mg 157.50 mg (150.0 mg 5 %)

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(mg/tablet
: Not more than two of the individual weight of 20 tablets deviate from
Weight variation average weight by more than 7.5% and none deviate by more than
15%
Thickness : 3.45mm 3.81 mm (3.63mm 5%)
Hardness : Not less than 5 Kg
Disintegration time : Not more than 15 minutes
Friability : Not more than 1.0 %
Description of : A green colored, round shaped, one side engraved with V and other
tablet side break line tablet
4. Coating
Compressed tablets are coated in PAM GLATT Coating machine by maintaining following Procedure:
Inlet Temperature Pan speed Duration Spray RPM Test parameter Remarks
400c 3 rpm 60 minutes 20 rpm
Appear uniform
color
Appearance,
weight gain
weight gain &
550c 1 rpm 15 minutes Off other parameter
as specification
5. Packaging Description
1. Cartons shall be overprinted with relevant information as follows
Name Batch Coding information
Inner carton for Ketofast 10 mg Tablet Batch No.
Mfg. Date
Exp. Date
IP/MRP Tk. (if not printed on Carton)
2. Blister strips of Ketofast 10 mg tablet shall be overprinted with relevant information as follows
Name Batch Coding information

Batch No.
Blister strip of Ketofast 10 mg Tablet
Exp
3. Primary and secondary packaging area will be free from previous packing
materials.
4. Coated tablets are packed in Blister Packing Machine (HOONGA) by maintaining
following specification. Sealing temperature : 1400C 1700C
Blister Forming Temperature: 1250c 1350c
5. After giving start up by Production and QA subsequently, Products will be packed
with relevant packing materials.
D) Manufacturing flow chart

PROCESS FLOW DIAGRAM
PROCESS STEPS EQUIPMENT
MATERIALS
Weighing balance All active and Excipients

DISPENSING

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SIEVING Ketorolac Tromethamine,

20 mesh screen Sodium Starch Glycolate,
Vibratory shifter Avicel PH 102)
DRY MIXING
Pillar Bin Blender Colloidal Silicon Dioxide,

Magnesium Stearate
LUBRICATION &
BLENDING
45 Station Cadmach Blended materials
Compression Machine
COMPRESSION HPMC (15 cps)

Methylene Clhloride
Methanol
Pam Glatt Polyethylene Glycole
Titanium dioxide
Purified Talc
COATING Green Lake
Coated Tablet, Packaging

Hoonga material
PACKING
QC TEST SAMPLE
12.0 SPECIAL PRECAUTION:

The product will manufacturing and filling with special precautions
13.0 PROCESS PARAMETERS FOR IPC TEST
All manufacturing process, record & specifications are given in Batch Manufacturing Record
(BMR)
14.0 ANALYTICAL TEST METHODS

The test method used for the analytical data evaluation of Ketofast 10 mg tablet is TP/PK 001/01
The parameters are evaluated according to the specification:
Item Ref. No.

Specification of Granules SPEC/PK 001/GR/00
Specification of Core Tablet SPEC/PK 001/IP/01
Specification of Coated Tablet SPEC/PK 001/CT/01
Specification of Finish Product SPEC/PK 001/FP/01
15.0 SAMPLING PLAN

15.1 Granulation Stage (Dry Mixing and Blending) & Follow the diagram below for sampling
Sampling Quantity of samples to
Sampling frequency
Point collect
Top 20 gm 2 set of sample from each point
Middle 20 gm 2 set of sample from each point
Bottom 20 gm 2 set of sample from each point

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1 & 2 = Top
3 & 4 = Middle
5 & 6 = Bottom
1 2
4 3
5 6
15.2 Compression Stage

Sampling Point Quantity of samples to collect Sampling frequency
Channel-1 ( Left) 100 tablets at each stage Start, middle and end of operation
Channel-2 ( right) 100 tablets at each stage Start, middle and end of operation
15.3 Coating
Sampling Point (After Quantity of samples to collect Sampling frequency
coating)
Top 100 tablets Three different places
Middle 100 tablets Three different places
Bottom 100 tablets Three different places
15.4 Blistering
Sampling Quantity of samples
Sampling frequency
Point to collect
Start of After start of operation, at 5 minutes interval (at
30 strips
operation least three times)
Middle of At middle of operation, at 5 minutes interval (at
30 strips
operation least three times)
End of 15 minutes before end of operation, at 5
30 strips
operation minutes interval (at least three times)
15.5 Finish Product
Sampling Point Quantity of samples to collect Sampling frequency
Start of operation 100 tablets Three different places
Middle of operation 100 tablets Three different places
End of operation 100 tablets Three different places
Deviation (if any):
16.1 Acceptance Criteria

Stage Test Parameter Acceptance criteria
Loss on drying
Not more than 3.5%
/Water content
Granulation 9.50mg 10.50mg (95.0% to 105.0% of the label claim)
Assay
RSD: NMT 3%
Identification Must be positive for Ketorolac Tromethamine
Compression Physical A green colored, round shaped, one side engraved with V
appearance and other side break line tablet
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Hardness NLT 5 kg
Thickness 3.45mm 3.81 mm (3.63mm 5%)
Average Weight 142.50mg 157.50 mg (150.0mg 5%)
Not more than two of the individual weight of 20 tablets
Weight variation deviate from average weight by more than 7.5% and none
deviate by more than 15%
Disintegration test Not more than 15 minutes
Assay 9.0mg 11.0mg (90.0% to 110.0% of the label claim)
Individual: 85% - 115% (10 dosage units)
If one unit is outside the limit but within 75% -125% then
test another 20 units individually.
Content uniformity
30 units: None should be outside of 75% - 125% of
average content (30 units) and maximum one can be
outside 85% -115% of average content (30 units).
Physical A green colored round shaped film coated tablet with one
appearance sides engraved V and other side break line
Average weight 152.0 mg 168.0 mg (160.0 mg 5 %)
Hardness Not less than 6 kg
Thickness 3.55 mm 3.93 mm (3.74 mm 5%)
Coating Not more than two of the individual weight of 20 tablets
Weight variation deviate from average weight by more than 7.5% and none
Dissolution Not less than 75% within 45 minutes
Pocket Formation Must be OK.
Blistering
Leak test Must be leak proof.
16.2 Finish Product Specification

Physical A green colored round shaped film coated tablet with one sides engraved V
appearance and other side break line
Not more than two of the individual weight of 20 tablets deviate from average
Weight variation
weight by more than 7.5% and none deviate by more than 15%
If one unit is outside the limit but within 75% -125% then test another 20 units
Content uniformity individually.
30 units: None should be outside of 75% - 125% of average content (30 units)
and maximum one can be outside 85% -115% of average content (30 units).
Primary packaging Alu-Pvdc
Pack size 2X10s
17.1 Set critical parameters at different conditions, justify the suitable one at which meets
specification and then run the machine at justified condition.
Sl. Control Variable Critical parameters to be checked

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No.
01 Dry mixing Time Mixing time

Lubrication &
02 Time Mixing time and speed (fixed)
blending
Machine speed and compression
03 Compression Pressure and turrent speed
pressure
Pan speed, inlet & Outlet temperature
04 Coating Pan speed and spay rate
and spray rate
Forming temperature,
Forming temperature, pressure &
05 Blistering pressure & sealing
sealing temperature
temperature

Rev No.: 00
17.2 CRITICAL PROCESS PARAMETERS AND JUSTIFICATION

The following process parameters shall be considered as "critical" because the uniform results meeting the acceptance criteria will depend upon
these parameters. Collect sample as per sampling plan (15.0) and carryout test (18.0) as per specification.

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Sl. Control Critical

Steps Desired set value Justification Acceptance criteria Result
No. Variable parameters
Check the moisture content, LOD/Moisture content: NMT 3.5%
Mix for 30 minutes, uniformity of granules by assay Assay: 9.50mg 10.50mg (95.0%
QC/QA will collect analysis. If does not meet
Dry to 105.0% of the label claim)
01 Time Mixing time sample as per sampling specification then mix for 5
mixing minutes & carryout test. From
RSD value is within 3%
plan and analyze as per
next batches, it will be mixing Identification: must be positive for
specification
time. Ketorolac Tromethamine
Check the moisture content,
Carryout blending for 10 uniformity of granules. Moisture LOD/Moisture content: NMT 3.5%
content & assay is within 5% of
Lubrication &
minutes, QC/QA will Assay: 9.50mg 10.50mg (95.0%

Mixing time theoretical values & RSD value is
blending
collect sample as per to 105.0% of the label claim)

02 Time and speed within 3%. If the result does not
sampling plan and meet specification then mix for
RSD value is within 3%
(fixed)
analyze as per another 5 minutes and carryout Identification: must be positive for
specification tests. From next batches, it will Ketorolac Tromethamine
be blending time.
Description: A green colored,

round shaped, one side engraved
with V and other side break line
Check all physical parameters
tablet
Run the like Description, Average
Hardness: NLT 5 kg
compression machine weight, Hardness, Thickness,
Compression
Thickness: 3.45mm 3.81 mm

Pressure Machine at 12, 16 & 20 RPM Friability, Disintegration time
(3.63mm 5%)
and speed and and pressure at 3 tons, and uniformity of weight at
03 Average weight: 142.50 mg
turrent compression QC/QA will collect each speed and pressure.
157.50 mg (150.0 mg 5%)
speed pressure sample as per sampling Define the speed & pressure
Weight variation: Not more than
plan and analyze as at which the results meet
two of the individual weight of 20
per specification specification. Then run the
tablets deviate from average weight
machine at defined conditions.
by more than 7.5% and none
Disintegration Time: NMT 15 min.

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Content Uniformity-
Run the compression machine Individual: 85% - 115% (10 dosage units)
Compression
Machine at 12, 16 & 20 RPM and If one unit is outside the limit but within 75%
Pressure
speed and pressure at 4 tons, QC/QA will -125% then test another 20 units individually.
03 and turret
compression collect sample as per sampling 30 units: None should be outside of 75% -
speed
pressure plan and analyze as per 125% of average content (30 units) and
specification maximum one can be outside 85% -115% of
average content (30 units).
Set Inlet temperature at 400c, pan
speed 3 rpm, spray rate 20 rpm for
60 minutes and QC/QA will collect
sample as per sampling plan and
carryout test as per specification
Set Inlet temperature at 430c, pan Description: A green colored, round shaped,
Check
speed 4 rpm, spray rate 25 rpm for one side engraved with V and other side
appearance
30 minutes and QC/QA will collect break line tablet
(Color
sample as per sampling plan and Hardness: NLT 5 kg
uniformity)
carryout test as per specification Thickness: 3.55mm 3.93 mm (3.74mm
at each
Pan speed, Set Inlet temperature at 450c, pan 5%)
Pan stage up to Average weight: 152.0 mg 168.0 mg
Coating
inlet & Outlet speed 5 rpm, spray rate 30 rpm for

speed completion
04 temperature 30 minutes and QC/QA will collect (160.0 mg 5%)
and spay of process.
and spray sample as per sampling plan and Weight variation: Not more than two of the
rate After that
rate carryout test as per specification individual weight of 20 tablets deviate from
carryout test
Set Inlet temperature at 500c, pan average weight by more than 7.5% and
as per
speed 6 rpm, spray rate 35 rpm for none deviate by more than 15%
sampling
60 minutes and QC/QA will collect Disintegration Time: NMT 15 min.
plan &
sample as per sampling plan and Dissolution: Not less than 75% within 45
specification
carryout test as per specification. min
Set Inlet temperature at 550c, pan
speed 1 rpm, sprays off for 15
minutes and QC/QA will collect
sample as per sampling plan and
carryout test as per specification

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18.0 Analysis of samples

18.1 Granulation Stage Analytical method Ref. No.:
Testing
Test
plan/sample Sample ID No. Result Range Acceptance criteria Pass/fail Remarks
parameters
preparation plan
Top-1 Not more than 3.5%
Top
Top-2
Loss on Carry out tests on
Middle-1
drying/Wate each sample ( 6 Middle
Middle-2
r content samples)
Bottom-1
Bottom
Bottom-2
Top-1 9.50mg 10.50mg
Top
Top-2 (95.0% to 105.0% of
Carry out tests on the label claim)
Middle-1
Assay each sample ( 6 Middle
Middle-2
samples) RSD: NMT 3%
Bottom-1
Bottom
Bottom-2
Must be positive for
Identificatio
Ketorolac
n
Tromethamine
18.2 Compression stage Batch No.:

Test Testing plan/sample Sample ID
Result Average Range Acceptance criteria Pass/fail Remarks
parameters preparation plan No.
Ch.-1 A green colored, round
Start
Ch.-2 shaped, one side
Physical Check at each sampling Middl Ch.-1 engraved with V and
appearance stage & each channel e Ch.-2 other side break line
Ch.-1 tablet
End
Ch.-2
Ch.-1 NLT 5 kg
Start
Ch.-2
Check at each sampling
Hardness Middl Ch.-1
stage & each channel
e Ch.-2
End Ch.-1

Rev No.: 00
Test Testing plan/sample Sample ID Pass

Result Average Range Acceptance criteria Remarks
parameters preparation plan No. /fail
Ch.-1 3.45mm 3.81 mm
Start
Ch.-2 (3.63mm 5%)
Check at each sampling Middl Ch.-1
Thickness
stage & each channel e Ch.-2
Ch.-1
End
Ch.-2
Average Weight 10 tabs at each Channel-1 142.50 mg 157.50 mg
weight stage from each channel Channel-2 (150.0 mg 5%)
Channel-1 Not more than two of the
individual weight of 20
Weight Sample from each stage at tablets deviate from average
variation each channel with 20 tabs. Channel-2 weight by more than 7.5%
and none deviate by more
than 15%
Ch.-1 Not more than 15 minutes
Start
Ch.-2
Disintegratio 6 samples from each stage Middl Ch.-1
n test at each channel e Ch.-2
Ch.-1
End
Ch.-2
Channel-1 9.50mg 10.50mg (95.0%
Composite of 20 tablets
to 105.0% of the label claim
Assay from each stage and
Channel-2 RSD: NMT 3%
channel
Individual: 85% - 115% (10
dosage units)
If one unit is outside the limit
but within 75% -125% then
Select 10 tablets from test another 20 units
Content composite sample collected individually.
Uniformity from different steps & 30 units: None should be
carryout assay of each unit. outside of 75% - 125% of
average content (30 units)
and maximum one can be
outside 85% -115% of

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18.3 Coating stage Batch No.:
Test Testing plan/sample Acceptance

Sample ID No. Result Average Range Pass/fail Remarks
parameters preparation plan criteria
Top A green colored
Middle round shaped film
coated tablet with
Physical Check at each sampling
one sides
appearance stage
End engraved V and
other side break
line
Top 152.0 mg 168.0
Average Weight 20 tabs at each
Middle mg (160.0 mg 5
weight stage
End %)
Top Not less than 6 kg
Sample from each stage
Hardness Middle
with 10 tablets
End
Top 3.55 mm 3.93
Thickness Middle mm (3.74 mm
with 10 tablets
End 5%)
Not more than two
Top of the individual
weight of 20
tablets deviate
Weight Sample from each stage
from average
variation with 20 tablets Middle
weight by more
than 7.5% and
End none deviate by
more than 15%
Top Not more than 30
Disintegratio
6 samples from each stage Middle minutes
n test
End
9.50mg
10.50mg (95.0%
Composite of 20 tablets
Assay Composite to 105.0% of the
from each stage
label claim)
RSD: NMT 3%
Composite of sample from Top Not less than 75%
Dissolution each stage (at 5, 10, 15, Middle within 45 minutes
30, 45 & 60 minutes) End

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18.4 Blistering
Test parameters Testing plan/sample preparation plan Result Acceptance criteria Pass/fail Remarks
Start of operation
Pocket Formation Middle of operation Must be OK.
End of operation
Start of operation
Middle of operation
End of operation
18.5 Finish Product
Test Testing plan/sample Sample ID Acceptance

Result Average Range Pass/fail Remarks
parameters preparation plan No. criteria
Top A green colored

round shaped film
Middle coated tablet with
Physical Check at each sampling
one sides
appearance stage
engraved V and
End other side break
line
Top 152.0 mg 168.0
Average Weight 20 tabs at each
Middle mg (160.0 mg 5
weight stage
End %)
Top
Hardness Middle Not less than 6 kg
with 10 tablets
End
Top 3.55 mm 3.93
Thickness Middle mm (3.74 mm
with 10 tablets
End 5%)
Not more than two
Top of the individual
weight of 20 tablets
Weight Sample from each stage Middle deviate from
variation with 20 tablets average weight by
more than 7.5%
End and none deviate
by more than 15%
Top
Disintegratio Not more than 30
6 samples from each stage Middle
n test minutes
End

Rev No.: 00
Testing
Test Sample ID
plan/sample Result Average Range Acceptance criteria Pass/fail Remarks
parameters No.
preparation plan
Composite of 20 9.50mg 10.50mg (95.0% to
Assay tablets from each Composite 105.0% of the label claim)
stage RSD: NMT 3%
Composite of Top
sample from each Middle
Not less than 75% within 45
Dissolution stage (at 5, 10, 15,
minutes
30, 45 & 60 End
minutes)
Individual: 85% - 115% (10
dosage units)
If one unit is outside the limit
Select 10 tablets but within 75% -125% then
from composite test another 20 units
Content sample collected individually.
Uniformity from different steps 30 units: None should be
& carryout assay of outside of 75% - 125% of
each unit. average content (30 units) and
maximum one can be outside
85% -115% of average
content (30 units).

Rev No.: 00
19.0 Summary of test result of individual batch Batch No.:

Resul Pass/Fai
Stage Test Parameter Acceptance criteria Remarks Deviation (if any)
t l
Loss on
drying/Water Not more than 3.5%
Granulation content
9.50mg 10.50mg (95.0% to 105.0% of the
Assay
label claim) RSD: NMT 3%
A green colored, round shaped, one side
Physical
engraved with V and other side break line
appearance
tablet
Hardness NLT 5 kg
Not more than two of the individual weight of 20
tablets deviate from average weight by more
Weight variation
than 7.5% and none deviate by more than
Compression 15%
9.50mg 10.50mg (95.0% to 105.0% of the
Assay
If one unit is outside the limit but within 75%
-125% then test another 20 units individually.
Content uniformity 30 units: None should be outside of 75% -
125% of average content (30 units) and
maximum one can be outside 85% -115% of
Coating A green colored round shaped film coated tablet
Physical
with one sides engraved V and other side
appearance
break line
Weight variation
15%
Assay 9.50mg 10.50mg (95.0% to 105.0% of the

Rev No.: 00
Resul Pass/Fai
Stage Test Parameter Acceptance criteria Remarks Deviation (if any)
t l
Blistering
A green colored round shaped film coated tablet
Physical
with one sides engraved V and other side
appearance
break line
Weight variation
15%
Finish
Product Disintegration test Not more than 30 minutes
9.50mg 10.50mg (95.0% to 105.0% of the
Assay
If one unit is outside the limit but within 75%
-125% then test another 20 units individually.
Content Uniformity 30 units: None should be outside of 75% -
125% of average content (30 units) and
maximum one can be outside 85% -115% of
20. Summary format of three validation batches
Result Deviation
Stage Test Parameter Acceptance criteria Pass/Fail Remarks
(if any)
Loss on
drying/Water Not more than 3.5%
Granulation content
9.50mg 10.50mg (95.0% to 105.0%
Assay
of the label claim) RSD: NMT 3%
Compression A green colored, round shaped, one
Physical
side engraved with V and other side
appearance
break line tablet
Hardness NLT 5 kg

Rev No.: 00

Not more than two of the individual
weight of 20 tablets deviate from
Weight variation
average weight by more than 7.5%
and none deviate by more than 15%
Result Deviation
(if any)
9.50mg 10.50mg (95.0% to 105.0%
Assay
Individual: 85% - 115% (10 dosage
units). If one unit is outside the limit
Compression but within 75% -125% then test
another 20 units individually.
Content uniformity 30 units: None should be outside of
75% - 125% of average content (30
units) and maximum one can be
outside 85% -115% of average content
(30 units).
A green colored round shaped film
Physical
coated tablet with one sides engraved
appearance
V and other side break line
152.0 mg 168.0 mg (160.0 mg 5
Average weight
%)
Coating Not more than two of the individual
Weight variation
9.50mg 10.50mg (95.0% to 105.0%
Assay
Blistering

Rev No.: 00
Result Deviation
(if any)
A green colored round shaped film
Physical
coated tablet with one sides engraved
appearance
V and other side break line
152.0 mg 168.0 mg (160.0 mg 5
Average weight
%)
Not more than two of the individual
Weight variation
Finish Disintegration test Not more than 30 minutes
Product 9.50mg 10.50mg (95.0% to 105.0%
Assay
Individual: 85% - 115% (10 dosage
units)
If one unit is outside the limit but within
75% -125% then test another 20 units
individually.
Content Uniformity
30 units: None should be outside of
75% - 125% of average content (30
units) and maximum one can be
outside 85% -115% of average content
(30 units).

Rev No.: 00
21. Reference documents

1) Raw data
2) Certificate of analysis for Granules, Core, Coated & Finish Product
3) Attachments
4) Analytical note book reference No.
5) Analytical note book No.
22.0 YIELD SUMMARY Batch No.:
Sl. No. Stage Specification Actual yield Pass/Fail Remarks

01 Granulation
02 Compression
03 Coating
Finish
04
Product
23.0 DEVIATION REPORTING

After careful study of all results a deviation report shall be prepared and documented in the following format
Deviation Type Problem Investigation Conclusion

Analytical
Process
24.0 Revalidation
The manufacturing process of Ketofast 10 Tablet shall be revalidated in one or more of following cases:
24.1 Change in formulation, procedure or quality of pharmaceutical ingredients
24.2 Change of equipment, addition of new equipment which affect the performance of equipment.
24.3 Major change of process parameter.
24.4 Change in site.
24.5 On appearance of negative quality trends.
24.6 On appearance of new findings based on current knowledge.
24.7 Batch size change implementation of these changes shall be carried out as per change control system.
24.8 Major changes in utility system (HVAC, purified water etc.)
24.9 Each change should be as per change control procedure.
25.0 REVIEW OF RESULTS AND REPORTING

Results collected from the three batches shall be reviewed and a validation report will be prepared,
Compliance to specification in all three batches shall validate the manufacturing process concurrently. The
validation report shall include the final conclusion and recommendation. Conclusion shall clearly state the
status of compliance to the validation protocol and its acceptance criteria.
26.0 FINAL SUMMARY REPORT

Final Summary report with conclusion and recommendation to be included in Validation report.
27.0 COMPILATION OF CONTROL DATA AND RECORDS

Control data and records of three batches to be compiled and compliance to be checked as per validation
protocol and its acceptance criteria.
28.0 BATCH ANALYSIS REPORT

Finished batch analysis report of three batches to be compiled and uniformity and RSD to be checked for
each parameter for compliance.

Rev No.: 00
29.0 FINAL APPROVAL
CERTIFICATE OF APPROVAL
Product : Ketofast 10 Tablet
Process : Granulation, Compression, Coating & Packing of Ketofast 10 mg Tablet
Reference : VPL-PVP-007
Prepared by:
Signature:________________
Sr. Executive, Product Development Date :________________
Checked by:
Assistant Manager, Quality Control Signature:________________
Date :________________
Agreed by:
Manager, Production Signature:________________
Date :________________
Approved by:
Quality Assurance Manager Signature:________________
Date :________________
cc: Head, Production

cc: Product Development
cc: Head, QA
30.0 APPENDICES
APPENDIX-1: Finished Batch Analysis Documents
APPENDIX-2: Control Data and Records
APPENDIX-3: Copies of Batch Documents
31.0 REVISION HISTORY

Version & Issue
Sl. No. Revision/Change in brief Reason for change
details
Version : 00, Date of
1 New N/A
issue: April 2014

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Veritas Pharmaceuticals limited Process Validation

VERITAS PHARMACEUTICALS LTD

Document Title: Process Validation Protocol of Ketofast 10

Prepared by Checked by Agreed by Approved by Date

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 1 of 26

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 2 of 26

2.0 Validation Team

Department Designation Responsibilities

5.0 Qualification and training of personnel

Name Designation Department Signature of Trainee Signature of Trainer

6.0 Calibration and qualification status of equipment and utility system

7.0 Batch details of validation batches

8.0 Qualification of starting materials

Name of the materials QC Ref. No. Release status Remarks

9.0 Details of reference / working standards

B) (i) Manufacturing formula

B) (ii) List of Coating materials

1117003 Green Lake 0.005

B) (iii) List of packaging materials

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 6 of 26

Name Batch Coding information

D) Manufacturing flow chart

Weighing balance All active and Excipients

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 7 of 26

SIEVING Ketorolac Tromethamine,

Pillar Bin Blender Colloidal Silicon Dioxide,

COMPRESSION HPMC (15 cps)

Coated Tablet, Packaging

12.0 SPECIAL PRECAUTION:

14.0 ANALYTICAL TEST METHODS

The parameters are evaluated according to the specification:

Item Ref. No.

15.0 SAMPLING PLAN

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 8 of 26

15.2 Compression Stage

16.1 Acceptance Criteria

16.2 Finish Product Specification

Sl. Control Variable Critical parameters to be checked

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 10 of 26

01 Dry mixing Time Mixing time

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 11 of 26

17.2 CRITICAL PROCESS PARAMETERS AND JUSTIFICATION

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 12 of 26

Sl. Control Critical

minutes, QC/QA will Assay: 9.50mg 10.50mg (95.0%

collect sample as per to 105.0% of the label claim)

Description: A green colored,

Thickness: 3.45mm 3.81 mm

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 13 of 26

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 14 of 26

inlet & Outlet speed 5 rpm, spray rate 30 rpm for

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 15 of 26

18.0 Analysis of samples

18.2 Compression stage Batch No.:

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 14 of 26

Test Testing plan/sample Sample ID Pass

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 15 of 26

18.3 Coating stage Batch No.:

Test Testing plan/sample Acceptance

Ketofast 10 Tablet COMPANY PROPRIETARY AND CONFIDENTIAL Page 16 of 26

18.5 Finish Product

Test Testing plan/sample Sample ID Acceptance

Top A green colored