COMPANY NAME Doc.Code : Revision No.

:
Document Name : Process Validation Protocol for XXX Tablet Issue Date :
Prepared By : Approved By : Page of

The pre - approval of this validation protocol is the joint responsibility of the following
Functional areas at ABC Co., Ltd.

PREPARED BY : __________________________________ DATE : _____________________

VALIDATION

REVIEWED BY : __________________________________ DATE : _____________________

PRODUCTION

REVIEWED BY : __________________________________ DATE : _____________________

QC

APPROVED BY : __________________________________ DATE : _____________________

QA
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TABLE OF CONTENT

TITLE :
1.0 OBJECTIVE
2.0 SCOPE
3.0 RESPONSIBILITY
4.0 GENERAL DOCUMENTATION
5.0 VALIDATION ACTIVITY SUPPORT
6.0 ACCEPTANCE CRITERIA
7.0 PROCEDURE
8.0 TEST FAILURE
9.0 REVALIDATION
10.0 REFERENCE
11.0 ATTACHMENT
COMPANY NAME Doc.Code : Revision No. :
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1.0 Objective
To demonstrate that the manufacturing process of XXX Tablet, operated within established parameters, can perform effectively and
reproducibly to produce product meeting its predetermined specifications and quality attributes.

2.0 Scope
This protocol is applies to manufacturing process of XXX Tablet, batch size X00,000 tablets described in Batch
Production Record code no. XXX Tablet 001, Issue date 20 December 2000.
Three consecutive successful trials will be conducted to demonstrate reproducible performance. Critical process parameters
will be monitored, tested and evaluated to verify the effectiveness of the manufacturing process.

3.0 Responsibility
3.1 Validation
• Prepare this protocol.
• Conduct the validation trials.
• In conjunction with QC, develop the sampling plan. (i.e. sampling location, sampling size and procedure
for collecting sample)
• Collect samples and send samples to QC for testing.
• Accumulate, compile and summarize all test results.
• Generate validation report and circulate for approval.
3.2 Production
• In conjunction with Validation, construct process flow diagram, identify critical process parameters.
• Schedule time availability to validation execution.
• Notify Validation of any major changes to the products, equipment, process or lot size.
3.3 QC
• Issue sampling plan and analytical method.
• Perform the physical, chemical and microbiological testing and supply test results to VA.

4.0 General documentation

4.1 Worksheets
Data other than laboratory data must be documented on one of the following types of worksheets during the
execution of the protocol.
4.1.1 Test data worksheets, provided in the Attachment 1, are to be used to collected data required by the
protocol.
4.1.2 A general data worksheets, Attachment 2, is to be used for additional data gathering or data clarification.
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4.2 Deviation report
A deviation report, Attachment 3, provides a detailed description of the incident, investigation as to the cause,
and evaluation of the deviation impact. It indicates the detection of discrepant results, methods, data collection
or information during the protocol execution. A deviation does not necessary deem the qualification as
unacceptable.

5.0 Validation activity support

5.1 All process equipment used are in qualification status. The instruments associated with process equipment
and manufacturing process are within their calibration interval.
5.2 All raw materials and components used in manufacturing the product have met their corresponding
specifications. They have been accurately weighed and dispensed.
5.3 The production batch record in conjunction with Standard Operating Procedures (SOPs) include all necessary
steps to manufacture the product.
5.4 The operators have been trained to perform the task that compliance with actual processing order, SOPs for
the process and SOPs for process equipment operation.

6.0 Acceptance criteria

Each validation trial is considered acceptable if all QC test results of raw materials, in - process product and final product meet the
predetermined specifications and all validation test results meet the acceptance criteria in the protocol. Three(3) consecutive
successful validation trials are required for conclusion.

7.0 Procedure
Document the process using an appropriate data worksheets include the following information :
• Process flow diagram. Prepare a process flow diagram including all processing steps, process parameters, test
parameters and major equipment used at each step.
• Equipment list. Prepare a list of the major used in each processing steps.
• Materials and component list. Document the ingredients and primary packaging components by lot number,
manufacturer, control number and specification number.
• Manufacturing process steps. The critical parameters in the key processing steps will be monitored, sampled
and evaluated on physical, chemical and microbiological basis.
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8.0 Test failure
If any of the results do not meet acceptance criteria, then a course of action must be proposed and agreed upon by the protocol
approvers.

9.0 Revalidation
Revalidation is required when any major change is taken such as critical process parameters, formulation
process equipment, manufacturing process and packaging materials (primary container/ closure system) that may
affect product quality and/ or the reproducibility of the process. Failure to meet product and process specifications
in sequential lots would also required process revalidation.

10.0 Reference
1. USA - FDA, guidelines on general principle of process validation, 1987.
2. Final Report on Blend Uniformity Recommendations FThe Use of Stratified Sampling of Blend and Dosage Units
to Demonstrate Adequacy of Mix for Powder BlendsG March 28, 2002, Blend Uniformity Working Group(BUWG),
Product Quality Research Institute(PQRI), www.pqri.org.

11.0 Attachment
Attachment 1 : Test data worksheet
Attachment 2 : General data worksheet
Attachment 3 : Deviation report

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Attachment 1
Test Data Worksheet
Product data :
Product name : XXX Tablet
Lot size : X00,000Hs
Production Record code no. XXX Tablet 001, Issue date 20 December 2000.
Lot no. : ______________________ Date : from _____________ till ___________
Validation trial no. : ___________________(1st, 2nd, 3rd)

Process equipment list :

N-code Calibration/ Cleaned Date

Qualification by
status
1. Mixer (1)
2. Hot Air Oven
3. Fitz mill with screen no.00 mm
4. Sieve size 00 mesh
5. Mixer (2)
6. Tablet press
7. Packing M/C
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Materials and component list :
These following materials have meet the established specifications. The materials were accurately weighed and dispensed.
1 Tablet Manufacturer and Control no. and Test according
(mg) Lot no. Specification no. to procedure no.

1. PVP
2. Methylparaben
3. Active Ingredient
4. Corn starch
5. Explotab
6. Magnesium stearate

7. Printed aluminium foil

8. Printed boxes
9. Leaflet

* Active ingredient calculated on potency 100% of XXX

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Process flow diagram :
The processing steps as well as process/ product parameters for manufacturing XXX Tablet are outlined in the flow diagram.

Process flow diagram Processing steps/Parameters

1. Tablet :
Binder preparation
Binder Appearance : Clear solution
Binder solution
preparation
Active Ingredient
Corn Starch

Mix 000 minutes in Mixer Premixing

Time :
Add Binder
Wet kneading
Time :
Mix 000 minutes Appearance : Damp mass

Wet screening
Sifting through Fitz Mill Screen no.:
Speed :

Drying
Drying Time :
Temperature :

Sifting through Fitz Mill Dry screening

Screen no.:
Speed : Medium

External part Sifting through 00 mesh sieve Final blending

Time :

Final Blending 000 minutes in mixer

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Process flow diagram Processing steps/Parameters

Preliminary Tableting Preliminary tableting : Inprocess Control Data

Tableting (begin)
Finished product testing :
Comply with finished product specification
Tableting (end) Mixing yield :

2. Packing

Finished Tablet

Strip packing
Preliminary strip/blister
packing Sealing Temperature :
Leak test :
Inspection : Remove the defects

Strip/blister packing
(end)

100% inspection : Remove the defects

Packaging yield :
Cartonning (begin)

Cartonning (end)
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Sampling/Testing Plan and Acceptance Criteria
1. Binder solution

Tests Sampling/Testing Plan Acceptance Criteria

Appearance Visually inspect binder solution Clear solution

2. Premixing

Tests Sampling/Testing Plan Acceptance Criteria

Appearance Visually inspect. Uniformly powder mixing.
Blend Uniformity 10 x 3x gm. (sampling 10 location; use sampling device) Mean + 10% ; SD < 3.8 %

3. Wet mixing

Tests Sampling/Testing Plan Acceptance Criteria

Appearance Visually inspect wet granulation in the sigma blade mixer. Uniformly granulated, no local over-wetting

4. Active Granules/Dried/Sifted

Tests Sampling/Testing Plan Acceptance Criteria

Appearance Visually inspect the granules in the containers. Granules are uniform with respect to sizes, color, etc.
Loss on Drying 3 x 10 gm. (take sample from top, middle, bottom) For Information
Size Distribution 1 x 100 gm. Medium size: 40-60 %, Fines: 30-50 %
(Take samples collectively from top, middle and bottom ).
Perform sieve analysis using sieves of various sizes.
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5. Final Blend
Tests Sampling/Testing Plan Acceptance Criteria
Appearance Visually inspect granules in the blender. Granules are uniform with respect to sizes, color, etc.
Bulk/Tapped 1 x 50 gm. (Take sample collectively from top, middle and For information: BD: NNN g/ml; TD: NNN g/ml
Density bottom blender or storage containers).
Check the measured volume (bulk density), then tap (drop)
moderately until the measured volume is constant
(tapped density).
% Compressibility (Using bulk/tapped density data) % Comp.: NMT 15 %; % Comp.: = (TD-BD)*100/BD
Blend Uniformity 10 x 3x gm. (Take representative samples separately from All results (as % target potency; TP) are within the
(BU) the blender or storage containers). mean result + 10% (absolute). Standard Deviation
Assay each blend sample individually without sub-dividing. (SD) : NMT 3.8 %

6. Compressed Tablets
Tests Sampling/Testing Plan Acceptance Criteria
Blend & Content 10 x 7 tablets (Take 7 tablets (including repeat samples) from First Stage:
Uniformity 10 locations throughout the compression cycle). Comply with product specifications (90 - 110 % label
All the units are previously weighed prior to assay. amount; LA).
Content Uniformity: 30 tablets
1. Each location mean is between 90 Q 110 % label
amount.
2. RSD of all individual results is not more than 4.8 %.
3. All individual values are between 85 Q 115 % label
amount (LA).
Second Stage:
Content Uniformity: 70 tablets
1. Each location mean is between 90 Q 110 % label
amount.
2. RSD of all individual results is not more than 5.4 %.
3. All 70 individual values are between 75 Q 125 % LA
and not less than (NLT) 68 individual values are
between 85 - 115 % LA.
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6. Compressed Tablets (continued)

Tests Sampling/Testing Acceptance Tests Sampling/Testing Plan

Plan Criteria
Composite
Segment 1 Segment 2 Segment 3
Samples
Item 1
Item 2
Item 3
Item 4
Item 5
Item 6 100Hs 100Hs 100Hs Follow product specs.
Item 7
Item 8
Item 9
Item 10
Microbial Count Total Aerobic Microbial Count : < 100 CFU/g

7. Strip/Blister Packaging

Tests Sampling/Testing Plan Acceptance Criteria

Appearance 000 strips/blisters are taken throughout the packing run.
Sampling everyday (Total sample size > 000 strips/blisters)
and check.

Each strip/blister looks completely sealed and
fully contain 10 tablets

Printed texts on aluminium foil strip/blister are
correct and in good quality
Critical defect : 0 unit
AQL = xxx % , confidence level > 90%
Major defect : Not more than 00 unit
AQL = xxx% , confidence level > 90%
Minor defect : Not more than 00 unit
AQL = xxx% , confidence level > 90%
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8. Cartonning

Tests Sampling/Testing Plan Acceptance Criteria

Appearance 000 boxes are taken throughout the cartonning run.
Sampling everyday (Total sample size > 000 boxes)
and check

Box is in good appearance, registering, coding
and printing are correct with leaflet insert.

Pack size in each box. Each packing looks
completely sealed and fully contain 10
Tablets. Printed texts on packaging
are correct and in good quality
Critical defect : 0 unit
AQL = xxx% , confidence level > 90%
Major defect : Not more than 00 unit
AQL = xxx% , confidence level > 90%
Minor defect : Not more than 00 units
AQL = xxx% , confidence level > 90%
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Blend uniformity and product uniformity through dosage unit data
Product name : XXX Tablet Lot no.: ___________________ Validation trial no.: ____________
Location : 1 Location : 2
Weight (mg) % content % content Weight (mg) % content % content
(non-correct) (weight correct) (non-correct) (weight correct)
Tablet 1 ___________ ___________ ____________ Tablet 1 ___________ ___________ ____________
Tablet 2 ___________ ___________ ____________ Tablet 2 ___________ ___________ ____________
Tablet 3 ___________ ___________ ____________ Tablet 3 ___________ ___________ ____________
Location mean ___________ ___________ ____________ Location mean ___________ ___________ ____________
Location : 3 Location : 4
Weight (mg) % content % content Weight (mg) % content % content
(non-correct) (weight correct) (non-correct) (weight correct)
Tablet 1 ___________ ___________ ____________ Tablet 1 ___________ ___________ ____________
Tablet 2 ___________ ___________ ____________ Tablet 2 ___________ ___________ ____________
Tablet 3 ___________ ___________ ____________ Tablet 3 ___________ ___________ ____________
Location mean ___________ ___________ ____________ Location mean ___________ ___________ ____________
Location : 5 Location : 6
Weight (mg) % content % content Weight (mg) % content % content
(non-correct) (weight correct) (non-correct) (weight correct)
Tablet 1 ___________ ___________ ____________ Tablet 1 ___________ ___________ ____________
Tablet 2 ___________ ___________ ____________ Tablet 2 ___________ ___________ ____________
Tablet 3 ___________ ___________ ____________ Tablet 3 ___________ ___________ ____________
Location mean ___________ ___________ ____________ Location mean ___________ ___________ ____________
Location : 7 Location : 8
Weight (mg) % content % content Weight (mg) % content % content
(non-correct) (weight correct) (non-correct) (weight correct)
Tablet 1 ___________ ___________ ____________ Tablet 1 ___________ ___________ ____________
Tablet 2 ___________ ___________ ____________ Tablet 2 ___________ ___________ ____________
Tablet 3 ___________ ___________ ____________ Tablet 3 ___________ ___________ ____________
Location mean ___________ ___________ ____________ Location mean ___________ ___________ ____________
Location : 9 Location : 10
Weight (mg) % content % content Weight (mg) % content % content
(non-correct) (weight correct) (non-correct) (weight correct)
Tablet 1 ___________ ___________ ____________ Tablet 1 ___________ ___________ ____________
Tablet 2 ___________ ___________ ____________ Tablet 2 ___________ ___________ ____________
Tablet 3 ___________ ___________ ____________ Tablet 3 ___________ ___________ ____________
Location mean ___________ ___________ ____________ Location mean ___________ ___________ ____________
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Packaging process testing : Strip/Blister packaging
Product name : XXX Tablet Lot no. : _________________ Validation trial no : ___________
Date/ Time Number of sample Appearance defects (state number and type of defect)
Critical (AQL = 0.5%) Major (AQL = 1.0%) Minor (AQL = 2.5%)

Total : _______ strips Number of defect : _______ Number of defect : _______ Number of defect : _______
Acceptance limit Zero Not more than 1 units Not more than 7 units
Result (Pass/ Fail)

Remark : Critical :
Major :
Minor :

Checked by : ________________ Date : ____________ Reviewed by : ________________ Date : ____________

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Packaging Process Testing : Cartonning

Product : XXX tablet Pack size : 1 x10Hs Lot no. : ____________ Validation trial no. : _______

Date/ Time Number of sample Appearance defects (state number and type of defect)
Critical (AQL = 0.5%) Major (AQL = 1.0%) Minor (AQL = 2.5%)

Total _______ boxes Number of defects : _______ Number of defects : _______ Number of defects : _______
Acceptance limit Zero Not more than 1 unit Not more than 7 unit
Result (yes/ no)

Remark : Critical :
Major :
Minor :

Checked by : ___________________ Date : _____________ Reviewed by : __________________ Date : ____________

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Attachment2
General Data Worksheet
Validation Batch No. : _________________ Product : ____________________ Date : __________________

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Recorded by : ______________________________________ Date : _______________________

Reviewed by : ______________________________________ Date : _______________________

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Attachment 3
Deviation Report
Deviation No. Deviation from : ( ) Procedure ( ) Acceptance Criteria
Describe deviations and any immediate investigation :

Written by : Date :
Describe recommended action, investigation and rationale :

Written by : Date :
Action to be taken :

Action by : Due Date :

Describe closure of deviation :

Validation Management Approval to proceed with protocol execution :

Approved by : Date :
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Processing Steps/ Testing/ Acceptance Criteria/ Results :
Processing steps Tests Acceptance criteria Results
1. Binder Solution
Appearance Clear solution Appearance : ________________________________________________

2. Premixing
Appearance Uniformly powder mixing. Appearance : ________________________________________________
Blend Uniformity Mean + 10% ; SD < 3.8 % Blend Uniformity :
Sample no. 1 : __________ % Sample no.2 : __________%
Sample no. 3 : __________ % Sample no.4 : __________%
Sample no. 5 : __________ % Sample no.6 : __________%
Sample no. 7 : __________ % Sample no.8 : __________%
Sample no. 9 : __________ % Sample no.10 : __________%

3. Wet Mixing
Appearance Uniformly granulated, no local over-wetting Appearance : ________________________________________________

4.Active Granules

Dried/sifted Appearance Granules are uniform with respect to sizes, color, etc. Appearance : ________________________________________________
Loss on Drying For Information Loss on Drying : _____________________________________________
Size Distribution Size Distribution : Pass through NN mesh : _______ %
For Information
000 mesh : _______ % 000 mesh : _______ %
000 mesh : _______ % 000 mesh : _______ %
000 mesh : _______ % 000 mesh : _______ %
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Processing steps Tests Acceptance criteria Results
5. Final Blend
Appearance Granules are uniform with respect to sizes, color, ect. Appearance : ________________________________________________
Bulk/Tapped Density For Information Bulk Density : ________________ Tapped Density : _______________
% Compressibility NMT 15% % Compressibility : __________________________________________
Blend Uniformity All result (as % Target Potency) are within the mean % TP : Sample no. 1 : __________ % Sample no.2 : __________%
result + 10 % (absolute) Sample no. 3 : __________ % Sample no.4 : __________%
SD : NMT 3.8 % Sample no. 5 : __________ % Sample no.6 : __________%
Sample no. 7 : __________ % Sample no.8 : __________%
Sample no. 9 : __________ % Sample no.10 : __________%
SD : ______________________________________________________
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Processing steps Tests Acceptance criteria Results

6.Tableting
Blend Uniformity Each location mean (weight-corrected) is between % LP : Sample no. 1 : __________ % Sample no.2 : __________%
90-110% LP Sample no. 3 : __________ % Sample no.4 : __________%
RSD of all individual results is not more than 4.8% Sample no. 5 : __________ % Sample no.6 : __________%

Content Uniformity All 60 individual values (as is) are between 85.0- Sample no. 7 : __________ % Sample no.8 : __________%
115.0% label claim and RSD of all individual results Sample no. 9 : __________ % Sample no.10 : __________%
is not more than 4.8 %. RSD : _____________________________________________________
Content Uniformity : _________________________________________

Segment 1 Segment 2 Segment 3

Item 1 Follow Product Specification Item 1 : _____________ ___________ ______________

Item 2 Item 2 : _____________ ___________ ______________

Item 3 Item 3 : _____________ ___________ ______________

Item 4 Item 4 : _____________ ___________ ______________

Item 5 Item 5 : _____________ ___________ ______________

Item 6 Item 6 : _____________ ___________ ______________

Item 7 Item 7 : _____________ ___________ ______________

Item 8 Item 8 : _____________ ___________ ______________

Item 9 Item 9 : _____________ ___________ ______________

Item 10 Item 10 : _____________ ___________ ______________

Microbial Count Total Aerobic Microbial Count : < 100 CFU/g. Microbial Count : __________ __________ __________
Pathogenic Bacteria : Absent
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Processing steps Tests Acceptance criteria Results
7. Strip packaging
Appearance Critical defect : 0 unit Machine speed : __________________________________________
AQL = xxx% , confidence level > 90%
Major defect : Not more than 00 unit Number of defects : __________________________________________
AQL = xxx% , confidence level > 90% Number of defects : __________________________________________
Minor defect : Not more than 00 units
AQL = xxx% , confidence level > 90% Number of defects : __________________________________________

8. Cartonning
Appearance Critical defect : 0 unit
AQL = xxx% , confidence level > 90% Number of defects : __________________________________________
Major defect : Not more than 00 unit
AQL = xxx% , confidence level > 90% Number of defects : __________________________________________
Minor defect : Not more than 00 units Number of defects : __________________________________________
AQL = xxx% , confidence level > 90%