xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx

QUALITY ASSURANCE
PROCESS VALIDATION PROTOCOL FOR TABLETS / Protocol No. : xxxxxxxxxxxxxxxxx
Rev. :00
Supersedes: NIL
Protocol prepared on: xxxxxxxxxx
Effective Date: xxxxxxxxxxxxx
Page 1 of 38

PROCESS

VALIDATION

PROTOCOL FOR TABLETS

Protocol No. / : / xxxxxxxx
Effective Date. / : / xxxxxxxxxxxx
TABLE OF CONTENTS
S.NO. / SECTION / Page No
1.  / Protocol approval
2.  / Purpose
3.  / Responsibilities
4.  / Requirements
5.  / Personnel Responsibilities
6.  / Validation parameters
7.  / Limits
8.  / Conclusion report

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

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.

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:

Batch Size:

Sr No / Ingredients/Excipients / Unit per Tablet / Std. Qty. / Overages / Dispensed
Quantity / Weight by / Checked 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

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
1. / Pre-blending / Blending time
RPM
Load size
Order of addition / Blend uniformity
2. / Granulating / Load size
Amount of granulating agent
Solvent addition rate
RPM
Granulation time / Density
Yield
3. / Drying / Initial temperature
Load size
Drying temperature program
Air flow program
Drying time
Cooling time / Density
Moisture content
Yield
4. / Sizing / Screen type
Screen size
Feed rate / Granule size distribution
Loose drying
Packed density
5. / Blending / Load size
RPM
Blending time / Blend uniformity
Flow characteristics
Particle size distribution
6. / Tableting / Compression rate
Granule feed rate
Pre-compression force
Compression force / Weight variation
Friability
Hardness
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

Sr. No. / Name of Equipment / Equipment ID. / Qualification details / SOP No
1 
2 
3 
4 
5 
6 
7 
8 
9 
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
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)
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
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 packing)
/ Sealing temperature
/ Seal integrity
/ Counter Checking from 10 Jars at different Time intervals
Sr. No / Process / Variable / Machine setting
( Control Variables) / Remarks
1  / Blend Manufacturing
Sifting / Visually Inspection / No visible foreign particulate matter is observed
Premixing Stage / Uniform mixing by Assay analysis / Variation between the results shall not be more than 2%
2  / Granulation
Binder Preparation
Granulation / Finely divided material without free powder and excessive wetted lumps.
Wet milling / Material was finely divided
Drying / Loss on drying / Between 2.0 to 5.0%
Dry milling / Finely divided granules are observed
Lubrication / Assay and Sieve analysis / Variation between the results shall not be more than 2%
3  / Tablet compression / Physical Parameter / Wt. Variation, Hardness, Thickness, DT, Dissolution and Assay
4  / Tablet coating / Weight gain, weight variation and DT
5  / Tablet packing / Leak Test

PREMIXING:

Sampling Qty.: -Depends on quantity required for analysis.

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
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom)
Total samples: 9 Samples

MIXING:

Sampling Qty.: -Depends on quantity required for analysis.

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
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom)
Total samples: 9 Samples

DRYING:

Sampling point for drying stage:

T2

Top View Sampling

B2

Top

B3

TOP VIEW

T3

T1

B1

Front side Bottom

----- Sampling Points

Sampling Qty.: -Depends on quantity required for analysis.

Sampling Time: - (bracketing the time between 2 to 3 intervals of total mixing time)

While Drying is on: -

After ____ minutes,

After ___ minutes,

After _____ minutes

______minutes
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom)
Total samples: 9 Samples

MILLING:

Sampling Qty.: -Depends on quantity required for analysis.

Sampling Time: - (bracketing the time between 2 to 3 intervals of total milling time)

While milling is on: -

After ____ minutes,

After ___ minutes,

After _____ minutes

______minutes
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom)
Total samples: 9 Samples

SAMPLING POINT FOR LUBRICATION (BLANDING) STAGE:

Name of Blender: (DOUBLE CONE BLENDER)

T2

Loading Valve

B3

Sampling Points

B2

B3

T3

T2

T1

M

T3

T1

T4

T1

B1

B4

B1

B2

B3

Sampling points T1, T2, T3 for top T4 B4 for middle, B1, B2, B3 for bottom sampling.
Sampling Qty.: -Depends on quantity required for analysis.

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
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom) / ______minutes
(Top , Middle & Bottom)
Total samples: 9 Samples

COMPRESSION:

Sampling Qty.: -Depends on quantity required for analysis.

Sampling Time: - (bracketing the time between 2 to 3 intervals of total compression time)

After ____ minutes,

After ___ minutes,

After _____ minutes

______minutes / ______minutes / ______minutes
Total samples: 3 Samples

COATING:

Sampling Qty.: -Depends on quantity required for analysis.

Sampling Time: - (Bracketing the time between 2 to 3 intervals of total coating time)

While coating is on: -

After ____ minutes,

After ___ minutes,

After _____ minutes

______minutes / ______minutes / ______minutes
Total samples: 3 Samples

Sampling:

Stage / Test Parameter / Equipment
(Size, Location & Time) / Acceptance Criteria
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:

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.


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


Result after mixing ______minutes

Sampling Detail / Results
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

Result after mixing ______minutes

Sampling Detail / Results
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation
Analyst: / Date

Remarks:

Checked By: ______Date: ______

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: ______


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)

Result after mixing ______minutes

Sampling Detail / Results
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

Result after mixing ______minutes

Sampling Detail / Results
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

Result after mixing ______minutes

Sampling Detail / Results
Top
Middle
Bottom
Mean
Standard Deviation
% Relative standard deviation

Remarks:

Checked By: ______Date: ______

Data recording sheet IV

Compression Stage / Date
______Station compression machine / :
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
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

Remarks: