Process Validation Protocol For Tablets: Protocol No. Effective Date

xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Protocol No. : xxxxxxxxxxxxxxxxx

Rev. :00
QUALITY ASSURANCE Supersedes: NIL
PROCESS VALIDATION PROTOCOL Protocol prepared on: xxxxxxxxxx
FOR TABLETS Effective Date: xxxxxxxxxxxxx
Page 1 of 38
PROCESS
VALIDATION
PROTOCOL FOR TABLETS
Protocol No. : xxxxxxxx
Effective Date. : xxxxxxxxxxxx
Prepared By Reviewed by Approved by
Designation QA chemist Production Manager Manager QC&A Plant head

Date
Format No.: xxxxxxxxxxxxxx

Rev. :00
Page 2 of 38
TABLE OF CONTENTS
Page
S.NO. SECTION
No
1. Protocol approval
2. Purpose
3. Responsibilities
4. Requirements
5. Personnel Responsibilities
6. Validation parameters
7. Limits
8. Conclusion report

Date

Rev. :00
Page 3 of 38
1. PROTOCOL APPROVAL
This document is prepared by the validation and the GMP compliance (QA) team of
xxxxxxxxxxxxxxxxx under the authority of Manager QC & A. Hence this document before being
effective shall be approved by xxxxxxxxxxxxxxx QA team.
Name Signature Date
Manager production
Manager Engineering
Manager QA

Date

Rev. :00
Page 4 of 38
2. PURPOSE
Process validation is establishing documented evidence which provides a high degree of assurance
that a specific process (such as manufacturer of pharmaceutical dosages forms) will consistently
produce a product meeting its predetermined specifications and quantity characteristics.
3. RESPONSIBILITIES
S.NO. Activity Responsibility

1. Preparation of protocol QA chemist
2. Chemical analysis and sampling QC chemist
3. Microbial analysis & sampling Microbiologist
4. Preparation of validation Report Dy Manager QC
5. Review of validation protocol & report QA department, Production Department
6. Approval of protocol & Report Plant Head
4. REQUIRMENTS: NIL
5. PERSONNEL RESPONSIBILITIES:
The perfect validation program necessitates various departments involvement mainly to balance the
total system functioning for its effective utilization for success criteria compliance on regular basis.
Quality assurance department initiates validation program with protocol, specified procedure and
success criteria. Quality control personnel are responsible for the validation run as per the protocol
and during validation maintenance departments have to cooperate to the quality control personnel.

Date

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Page 5 of 38
6. VALIDATION PARAMETERS:
Process Description / Flow Sheet
The information given below provides a general description of the process. Detailed information for
the manufacturing will be supplied separately in the Batch Processing Record.
1 Prepare production order and according to that issue the BPR
2 RM dispensing as per Bill of material
3 Input check in presence of QA person
4 Granulation
4.1 Sifting
4.2 Pre–mixing
4.3. (a) Wet granulation
Binder Preparation
Mixing
Wet milling
Drying
Dry milling
Slugging, Milling (if required)
Lubrication
4.3 (b) Dry Granulation
Mixing
Slugging, Milling (if required)
Lubrication
5 Tablet compression
6 Tablet coating
7 Tablet packing
Formulation:

Date

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Batch Size:
Sr Ingredients/Excipients Unit per Std. Overages Dispensed Weight Checked
No Tablet Qty. Quantity by by
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
FLOW SHEET:
Prepare production order and according RM dispensing as per Bill of material
to that issue the BPR

Date

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Page 7 of 38
Input check in presence of QA person GRANULATION

Shifting
Dry Granulation Premixing
Mixing Binder preparation

Wet Granulation milling
Drying
Dry milling Slugging, Milling (if required)
Mixing
Coating Compression Lubrication

(Blending)
Tablet packing
Sampling point
Typical Variables and responses: Granulated Product
S. No. Process step Control variables Measured responses

Date

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Page 8 of 38
1. Pre-blending Blending time Blend uniformity

RPM
Load size
Order of addition
2. Granulating Load size Density
Amount of granulating agent Yield
Solvent addition rate
RPM
Granulation time
3. Drying Initial temperature Density
Load size Moisture content
Drying temperature program Yield
Air flow program
Drying time
Cooling time
4. Sizing Screen type Granule size distribution
Screen size Loose drying
Feed rate Packed density
5. Blending Load size Blend uniformity
RPM Flow characteristics
Blending time Particle size distribution
6. Tableting Compression rate Weight variation
Granule feed rate Friability
Pre-compression force Hardness
Compression force Thickness
Disintegration time
Dissolution
Dosage from uniformity
Equipments
A detailed list of equipment used for validation together with the cleaning status will be provided in the
manufacturing documents.
List of SOP’S, Validation & Qualification report used as references

Date

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Page 9 of 38
Sr. No. Name of Equipment Equipment ID. Qualification details SOP No

1
10
11
12
Critical Process Parameters:

Critical stages: Following critical stages required to be validated to provide a high degree of assurance
for the manufacturing of tablets.
Sr. No. STAGE Parameters

1. Premixing RPM of mixer blade

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Load size
Total time of mixing
Uniform mixing by Assay analysis
2. Granulation Mixer blade speed
Load size
Binder Quantity
Binder addition rate
Binder addition time
Temperature of binder
Mixing time after binder addition /Total granulation time
Uniformity of granulated mass (Visual Checking)
3. Drying Dryer outlet temperature
Dryer inlet temperature
Drying load
Total drying time
Weight of the Dried granules
4. Milling Speed of machine
Direction of knives
5. Lubrication Load size
Occupancy
Speed of equipment (RPM)
Total time of mixing
Assay - (individual sample)

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6. Compression Temperature of area

Humidity of area
Machine Details
Weight variation of 20 tablets
Average weight of tablet
Disintegration time
Friability
Diameter (Length)
Thickness
Hardness
Assay
Content uniformity
Dissolution
7. Coating Temperature of area
Temperature of blower
Speed of Coating Pan (RPM)
Spray Rate
Bed Temperature
Air Pressure
Total Coating solution used
Weight Built up
Weight variation of 20 tablets
Assay

Date

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Disintegration time
Dissolution
8. Packaging Forming roller temperature. (for Blister Packing)
Sealing roller temperature
Sealing roller Pressure
Speed of machine
Seal integrity
Assay
Dissolution
9. Packaging (bulk Sealing temperature
packing)
Seal integrity
Counter Checking from 10 Jars at different Time intervals

Date

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Page 13 of 38
Machine setting
Sr. No Process / Variable Remarks
( Control Variables)
Blend Manufacturing
Sifting No visible foreign particulate
Visually Inspection
matter is observed
1
Premixing Stage
Variation between the results
Uniform mixing by Assay analysis
shall not be more than 2%
Granulation
Binder Preparation
Granulation Finely divided material without free
powder and excessive wetted lumps.
2 Wet milling Material was finely divided
Drying Loss on drying Between 2.0 to 5.0%
Dry milling Finely divided granules are observed
Lubrication Variation between the results
Assay and Sieve analysis
shall not be more than 2%
Wt. Variation, Hardness,
3 Tablet compression Physical Parameter Thickness, DT, Dissolution
and Assay
Weight gain, weight variation
4 Tablet coating
and DT
5 Tablet packing Leak Test
PREMIXING:
Sampling Qty.: -Depends on quantity required for analysis.

Date

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Page 14 of 38
Sampling Time: - (bracketing the time between 2 to 3 intervals of total mixing time)
While mixing is on: -
After ____ minutes,
After ___ minutes,
After _____ minutes
______ minutes _______ minutes ______ minutes
(Top , Middle & Bottom) (Top , Middle & Bottom) (Top , Middle & Bottom)
Total samples: 9 Samples
MIXING:
After ____ minutes,
After ___ minutes,
After _____ minutes
DRYING:
Sampling point for drying stage:
T2

Date

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Top View Sampling

Top B2
B3
TOP VIEW
T1 T3
Front side Bottom B1
----- Sampling Points

While Drying is on: -
After ____ minutes,
After ___ minutes,
After _____ minutes
MILLING:
Sampling Time: - (bracketing the time between 2 to 3 intervals of total milling time)
While milling is on: -

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After ____ minutes,

After ___ minutes,
After _____ minutes

SAMPLING POINT FOR LUBRICATION (BLANDING) STAGE:

Name of Blender: (DOUBLE CONE BLENDER)
Loading Valve T2
Sampling Points
Prepared By Reviewed by Approved by B3

Date

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Page 17 of 38
B2
T3
T2 T1
M
T4 T3
T1
T
1 B1
B4
B2 B3
B1
Sampling points T1, T2, T3 for top T4 B4 for middle, B1, B2, B3 for bottom sampling.

Date

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After ____ minutes,
After ___ minutes,
After _____ minutes
COMPRESSION:
Sampling Time: - (bracketing the time between 2 to 3 intervals of total compression time)
After ____ minutes,
After ___ minutes,
After _____ minutes
COATING:

Date

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Page 19 of 38

Sampling Time: - (Bracketing the time between 2 to 3 intervals of total coating time)
While coating is on: -
After ____ minutes,
After ___ minutes,
After _____ minutes
Sampling:
Stage / Test Parameter Equipment Acceptance Criteria
(Size, Location & Time)
Premixing Stage Variation between the results of Assay shall
not be more than 2%
Mixing
Drying Loss on drying Between 2.0 to 4.0%
Mixing
Lubrication Variation between the results of assay shall
not be more than 2%
Tablet compression Physical Parameter (I.P.Q.C)
Tablet coating Weight Gain
Tablet packing Leak Test
Recording of data & Data treatment:

Data Recording:

Date

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Page 20 of 38
The data obtained from the various analysis & observations shall be recorded in the Data
recording sheet for first three commercial batches.
Data Recording Sheet No.

Sheet No 1 For recording Mixing stage data
Sheet No 2 For recording Loss on drying data
Sheet No 3 For recording Lubrication stage data
Sheet No 4 For recording Compression stage data
Sheet No 5 For recording Coating stage data
Sheet No 6 For recording Packing stage data
Sheet No 7 For recording of analysis report
Sheet No 8 For recording general utilities /equipment / method qualitical
/results.
Sheet No 9 For recording analytical method validation.

Date

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Data recording sheet no I

Mixing Stage: Date
Equipment name :
Identification no :
Ingredients and sequence of material addition :
RPM of Mixer Blade :
Capacity :
Mixing time : Minutes
Standard Weight of Tablet :
Method reference: As per assay procedure given in finished product specification.
Blended material to be analyzed for ______________________________
Plan: Samples to be drawn of mixing from 3 different locations (Top, Middle & Bottom)
Result after mixing _________________ minutes
Sampling Detail Results
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

Date

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Page 22 of 38

Top
Middle
Bottom
Mean
Standard Deviation

Top
Middle
Bottom
Mean
Standard Deviation
Analyst: Date
Remarks:
Checked By: _________________________ Date: ____________________

Date

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Page 23 of 38
Data recording sheet no II

Loss on Drying Stage: Date
Equipment name :
Dryer outlet temperature :
Dryer inlet temperature :
Drying Load :
Total Drying time : Minutes
Weight of the dried granules :
Method reference: Loss on drying procedure by IR moisture balance.
Plan: Material to be analyzed for Loss on drying
Samples to be drawn from 3 different locations
Sample East West North South Average Limit

Weight taken
% LOD
Remarks:
Checked By: _________________________ Date: ____________________

Date

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Page 24 of 38
Data recording sheet III

Lubrication Stage: Date
Equipment name :
Identification no :
Capacity :
Occupancy :
Speed of equipment :
Mixing time : Minutes
Standard Weight of Tablet :
Method reference: As per assay procedure given in finished product specification.
Lubricated material to be analyzed for % of active content ______________________________
Plan: Samples to be drawn at of blender from 3 different locations (Top, Middle & Bottom)

Top
Middle
Bottom

Date

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Page 25 of 38
Mean
Standard Deviation

Top
Middle
Bottom
Mean
Standard Deviation

Top
Middle
Bottom
Mean

Date

Rev. :00
Page 26 of 38
Standard Deviation
Remarks:
Checked By: _________________________ Date: ____________________
Data recording sheet IV

Compression Stage Date
________ Station compression machine :

Date

Rev. :00
Page 27 of 38
Identification no :
Capacity :
RPM : 13 to 28 RPM
Punch Size :
Temperature of area :
Humidity of area :
Weight of 20 Tablets :
Average Weight of tablet :
Disintegration Time : NMT 15 minutes
Dissolution (If required) :
Friability : NMT 1.0%
Thickness :
Hardness :
Assay :
Content of uniformity (If required) :
Method reference: As per In-process check procedure.
Plan: Compressed tablets to be analyzed for: Average weight, Weight variation and Physical parameter
at an interval of 2 hours
Requirement RPM: RPM: RPM:
Time

Date

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Page 28 of 38
Average weight
Thickness mm
Hardness in kg./sq. cm2

Friability in %
DT in min.
Weight variation after validated RPM __________
Time Average Weight Thickness Hardness Friability Disintegration
Weight variation:
Time Time Time Time Time

Date

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Page 29 of 38
Remarks:
Checked By: _________________________ Date: ____________________
Data recording sheet V

Coating Stage Date
Name of equipment :
Identification no :
Capacity :

Date

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Page 30 of 38
Speed of coating pan :

Temperature of area :
Temperature of blower :
Spray rate :
Bed temperature :
Air Pressure :
Total coating solution used :
Weight build up :
Weight of 20 Tablets :
Average Weight of tablet :
Disintegration Time : Not more than
Dissolution (If required) :
Assay
Plan: Coated tablets to be analyzed for Weight gain, weight variation and DT. At an interval of __ hours
Date Time Initial Average Final Average % Weight gain DT in min.

weight weight weight weight

Date

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Page 31 of 38
Weight variation:
Time
Weight variation
Remark:
Checked By: _________________________ Date: ____________________

Date

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Page 32 of 38
Data recording sheet VI

Packing Stage Date
Name of equipment :
Identification no :
Capacity :
Forming roller temperature (For blister packing) :
Sealing roller temperature :
Sealing roller pressure :
Speed of machine :
Seal integrity (Leak test) :

Plan: Packed tablets to be analysed for Leak test at an interval of __ hours
Date Time Leak Test Results Remarks

No of strips to be
taken

Date

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Page 33 of 38
Data recording sheet VII

Analysis Report
Product Name:
Batch No.: Batch size:
Mfg. Date: Exp. Date:
Composition:
Test method reference: In house
Sr. No. Test Specification Results Remark
01 Description
02
03
04
05
5.1
5.2
5.3
5.4
Remark:
Result: The sample referred above complies / does not comply with the standard prescribed as per In
house Specification.
Data recording sheet VIII

Date

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Page 34 of 38
Sr Name of critical equipment / Utilities Qualification / Date of Qualification /

No Validation file Validation
reference No
1
10
11
12
13
14
Sr Name of critical equipment / Utilities Qualification / Validation Date of Qualification /
No file reference No Validation
15

Date

Rev. :00
Page 35 of 38
16
17
18
19
20
21
22
23
24
25
26
27
28
Utilities:
1 AHU System
2 Water System
3 Compressed Air
4 Steam
5 Lightning
6 Drain
Data recording sheet IX

Date

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Page 36 of 38
Remark:
Analytical Method Validation protocol attached

Date

Rev. :00
Page 37 of 38
Conclusion
Sr. No. Stage Acceptance criteria Observation

1. Sifting No visible foreign particulate matter is observed
2. Premixing Variation between the results shall not be more
Stage than 2%
3. Drying Between 2.0 to 4.0%
4. Lubrication Variation between the results shall not be more
than 2%
5. Tablet Average weight of tablets is within ± ____of std.
compression weight.
Tablets shall meet requirement of physical
parameter and FP specification.
6. Tablet coating Tablets shall meet the requirements for weight
gain, weight variation and disintegration.
Coated tablets shall meet FP Specification
7. Tablet Packed tablet shall meet the requirement for leak
packing test
Conclusion:
Product _________________________________ manufactured as per B.M.R. No _____________
meets predefined acceptance criteria.
Analysis By Approved By
Date Date

Date

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Page 38 of 38
7. LIMITS: As pre relative STPs
8. CONCLUSION REPORT
Summary report will contain discussion and conclusion , which clearly states the successful
achievement of objective of validation studies and recommended concentrations required for
sanitization, disinfections and equipment sanitization.
Note: Extra pages for conclusions can be used as per requirement.

Date

Process Validation Protocol For Tablets: Protocol No. Effective Date

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xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx

Protocol No. : xxxxxxxxxxxxxxxxx

Protocol No. : xxxxxxxx

Effective Date. : xxxxxxxxxxxx

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Name Signature Date

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

S.NO. Activity Responsibility

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Input check in presence of QA person GRANULATION

Dry Granulation Premixing

Mixing Binder preparation

Coating Compression Lubrication

Typical Variables and responses: Granulated Product

S. No. Process step Control variables Measured responses

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

1. Pre-blending Blending time Blend uniformity

List of SOP’S, Validation & Qualification report used as references

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Sr. No. Name of Equipment Equipment ID. Qualification details SOP No

Critical Process Parameters:

Sr. No. STAGE Parameters

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

6. Compression Temperature of area

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Counter Checking from 10 Jars at different Time intervals

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Prepared By Reviewed by Approved by

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Sampling point for drying stage:

Designation QA chemist Production Manager Manager QC&A Plant head

Protocol No. : xxxxxxxxxxxxxxxxx

Top View Sampling

Front side Bottom B1

----- Sampling Points

__ minutes _ minutes ____ minutes

Checked By: _____ Date:

Checked By: _____ Date: