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Protocol No.: Process Validation Protocol for Oral liquid/Suspension

Quality Assurance Department Page 1 of 24
Title : Validation Protocol for B. No. :

Formulation: Oral Liquid

Product’s Name:
Reason for Performing the Validity Study:
Reason ( tick which ever is applicable) Remarks
Department
New product
Modification in the manufacturing process.
Change in Facility and / or location of manufacturing.
Batch fails to meet product & process specifications.

Number of batches studied: First Three Batches

Batch numbers: 1. 2. 3.
Validation activity Approved by: _____________________________Date:_______________________
Validation Team:
Department Validation Team
Production

Quality Control

Quality Assurance

Approvals:
Department Sign & Date
Production
Engineering
Quality Control
Quality Assurance

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 2 of 24
Title : Validation Protocol for B. No. :

1.0 General:
1.1 Introduction:
The process validation will be performed as prospective validation. The complete documentation for the
validation comprises several independent documents; references to relevant documents will be given as
part of this protocol, (see below). The results of the validation activities will be summarized in the
validation report.

1.2 List of Documents for Validation:

Validation protocol,

Details of sampling for the validation batches, test parameters (Product performance characteristics)
with reference to test methods & Acceptance criteria. (acceptable Limit)

Methods for recording / evaluating results including statistical analysis.

Reference to relevant documents.

1.2.2 Batch manufacturing records.

Detailed manufacturing instructions for the production of the validation batches.

2.0 Personnel Responsibilities:

Sr Activity Responsibility Remarks

No
1 Preparation of validation protocol QA Department
2 Review of validation report. Q.A In charge
3 Production of validation Batches Production In charge
4 Testing of validation samples & Q.C In charge
Preparation of validation report
5 Approval of Validation protocol Manager (Q.A)

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 3 of 24
Title : Validation Protocol for B. No. :

3.0 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 manufacturing record.

1 DISPENSING OF MATERIAL

2 SUGAR SYRUP PREPARATION

3 BULK MANUFACTURING

4 PH ADJUSTMENT

5 VOLUME MAKE UP

6 FILTRATION

7 WASHING, FILLING AND SEALING

3.1 Formulation:
Batch Size:

Sr Ingredients/Excipients Unit per Quantity Overages Quantity Dispensed Function

No ml in Kgs with Quantity
Overages
1
2
3
4
5

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 4 of 24
Title : Validation Protocol for B. No. :

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Note:

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 5 of 24
Title : Validation Protocol for B. No. :

3.2 FLOW SHEET:

MANUFACTURING PROCESS DIAGRAM:- _________________syrup

Receipt and holding Dispensing Of Raw

of materials Material

Syrup Preparation
Excipient and active
addition

Colour & Flavour

Materials

Bulk Preparation &

Final Volume Make up

Final Mixing

Filtration Through Filter Press

Cleaning And Setting Of Filling Of Bulk Inspection Testing

Filling, Sealing, Labeling Into Bottles
Machine

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 6 of 24
Title : Validation Protocol for B. No. :

4.0 Equipments/ Factory

A detailed list of equipment used for validation together with the cleaning status will be provided in the
manufacturing documents.

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

SrNo Equipment Equipment No. SOP No
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 7 of 24
Title : Validation Protocol for B. No. :

4.2 Details of equipment to be used.

Equipment Details
S.S. Manufacturing Tank Type :
Model:
Capacity:
Manufacturer:
Tag No.
RPM
M.O.C.
S.S. Storage Tank Type :
Model:
Capacity:
Manufacturer:
Tag No.
RPM
M.O.C.
Filter Press Type :
Model:
Capacity:
Manufacturer:
Tag No.
Type of filter
M.O.C.
Transfer Pump Type :
Model:
Capacity:
Manufacturer:
Tag No.
M.O.C.
Washing Machine Type :

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 8 of 24
Title : Validation Protocol for B. No. :

Model:
Capacity:
Manufacturer:
Tag No.
Speed
M.O.C.
Filling Machine Type :
Model:
Capacity:
Manufacturer:
Tag No.
Speed
M.O.C.
Sealing Machine Type :
Model:
Capacity:
Manufacturer:
Tag No.
M.O.C.
Labeling Machine Type :
Model:
Capacity:
Manufacturer:
Tag No.
M.O.C.

Remarks:

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 9 of 24
Title : Validation Protocol for B. No. :

4.3 Identification of Critical process variables parameter.

4.3.1 Probable causes that may effect final product:

DISPENSING OF SUGAR SYRUP ADDITION OF ADDITION OF WASHING,

MATERIAL PREPARATION ACTIVE FLAVOUR & FILLING &
COLOUR SEALING

LOAD SIZE

SPEED

FINAL WASH
ACTIVE
STIRRER
CLARITY

PH & TEMP. VOLUME

MIXING
EXCIPIENT R.P.M. TIME

LEAKAGE
CLARITY
SEALING &
THRADING
MIXING TIME

R.P.M. R.P.M.
DIP
STICK

T MIXING TIME PH
E
M
P. SCREEN SIZE VOLUME

ADDITION OF pH ADJUSTMENT VOLUME MAKEUP

EXCIPEINT & FINAL MIXING

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 10 of 24
Title : Validation Protocol for B. No. :

Critical Process PARAMETERS:

Sr
Critical process variable Response parameter Remarks
No
Sugar Syrup Preparation
Fixed speed.
Mixing time
1
Load charge in to a Blender Uniformity of sugar
Fixed batch size

Final mixing and volume make up

Uniformity of Active
2 Mixing time Fixed speed.
Drugs
Load charge in to a Blender
Fixed batch size
Washing Fixed pressure for washing.
D.M. Water pressure Fixed temperature for washing
D.M. Water temperature Cleaning Of Bottle Fixed pressure of air
3 Fixed cycle
Compressed air pressure Washing efficiency
Washing cycle Fixed direction
Alignment & blockage of needles
Filling & Sealing Fixed speed
4 Speed of filling machine Volume variation
Volume Uniformity
Leak test Leakage
Clean, Position & Clean Label
5 Labeling & Packing Proper Sealing Position
Sealing

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 11 of 24
Title : Validation Protocol for B. No. :

Sr Machine setting
Process / Variable Remarks
No ( Control Variables)
Mixing Time
1 Sugar syrup preparation
Temperature
Manufacturing
Mixing Time
2 Load time
Mixing time

Bottle washing Washing Pressure

3

4 Bottle filling & Sealing Adjustment Of Volume

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 12 of 24
Title : Validation Protocol for B. No. :

5.0 Sampling, Test Parameters, Acceptance criteria

5.1 Sampling locations:

1. TOP –SAMPLE A

2. MIDDLE –SAMPLE B

3. BOTTAM –SAMPLE C

BOTTOM VALVE

Sampling site: - Top (A), Middle (B), Bottom(C) position; use the sample tube for A&B
and bottom valve for Position C
Sampling Qty.: -About 100 ml from each sample site
Sampling Time: - While mixing is on: - After ____ minutes, after ____ minutes, After _____ minutes
__________ minutes A,B & C ____________minutes A,B & C ________ minutes A,B & C
Total samples:________

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 13 of 24
Title : Validation Protocol for B. No. :

5.2 Sampling:

Stage / Test Parameter Equipment Acceptance Criteria

(Size, Location & Time)
Sugar syrup Preparation Determination on each sample, for Not more than ______
temperature, & Clarity minutes
Manufacturing Sampling thief
Appearance  As specified in the BMR
pH  Ref. std. :
weight per ml  As specified in the BMR
Identification  As per standard testing
procedure
Assay  Assay 90 % to 110 %

Bottle washing Visual inspection inspected for particulate

matter
Filling & sealing
Volume Measuring cylinder Not less than label claim.
Appearance Visual inspection, As specified in the BMR.
Odour Visual inspection As specified in the BMR
Colour Visual inspection As specified in the BMR
Capping Leak test Complies leak test
Cap breaking and recapping
Labeling & Packing Clean, Position & Proper Sealing Clean label and proper sealing

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 14 of 24
Title : Validation Protocol for B. No. :

6.0 Recording of data & Data treatment:

6.1 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 sugar syrup preparation & results
Sheet No 2 For recording of bulk manufacturing and results
Sheet No 3 For recording of bottle washing and results
Sheet No 4 For recording of bottle filling and sealing
Sheet No 5 For recording of capping
Sheet No 6 For recording of labeling and packing
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.

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 15 of 24
Title : Validation Protocol for B. No. :

Data recording sheet no I

Sugar syrup preparation:
Equipment name :_______________________
Identification no :_______________________ Date:____________________
Capacity : ______________________lt.
Ingredients and sequence of material addition: ____________________
Total Volume of ingredients : _______________ltr.
Mixing time : _______ minutes
Setting – stirrer : slow
Procedure : As outlined in the batch manufacturing record.
Plan : Samples to be drawn at of ___ minutes of mixing from 3 x 100 ml different
locations
For Sugar syrup preparation:
Result after mixing _________________ minutes
Points Temperature Clarity Weight per ml
Sample A
Sample B
Sample C

Analyst: Date

Conclusions:

Checked By: _________________________ Date: ____________________

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 16 of 24
Title : Validation Protocol for B. No. :

Data recording sheet no II

Manufacturing (Manufacturing Tank):
Equipment Name :_________________________
Identification no :_________________________ Date:___________________
Capacity : ______________________lt.
Ingredients and sequence of material addition: ____________________
Total weight of ingredients : _______________ltr.
Mixing time : ______ minutes
Setting – stirrer : slow
Procedure : As outlined in the batch manufacturing record.
Plan : Samples to be drawn at of _______ minutes, _______ minutes, & ______
minutes of mixing from 3 different locations
For manufacturing tank result:
Assay of after mixing ____________ minutes
Location Appearance pH Weight per ml Identification Assay
Between Between 90 to 110%
to to
Top
Middle
Bottom
Mean
Standard
Deviation
% Relative
standard deviation

N.B. Calculation sheet attached

Assay of after mixing ____________ minutes

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 17 of 24
Title : Validation Protocol for B. No. :

Location Appearance pH Weight per ml Identification Assay

Between Between 90 to 110%
to to
Top
Middle
Bottom
Mean
Standard
Deviation
% Relative
standard deviation

N.B. Calculation sheet attached

Assay of after mixing ____________ minutes
Location Appearance pH Weight per ml Identification Assay
Between Between 90 to 110%
to to
Top
Middle
Bottom
Mean
Standard
Deviation
% Relative
standard deviation

N.B. Calculation sheet attached

Conclusion:

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 18 of 24
Title : Validation Protocol for B. No. :

Data recording sheet III

Equipment Name: Bottle washing Machine
Identification no :_________________________ Date:___________________
Capacity : ______________________ (Bottle per minutes)
Method reference: Visual inspection.

Observation : Washed bottle shall be inspected for particulate matter.

Stage Inspected 1 2 3 4 5 6 7 8 9 10
by
After machine
setting
Beginning of
washing
Middle of
washing
End of washing

Conclusion:

Data recording sheet IV

Equipment Name: Monoblock filling & sealing machine
Identification no: ________________________________
Machine Speed:____________________
Standard volume: ________________ ml

Procedure: As per In-process check procedure for volume check.

Observation: Volume shall be more than label claimed.

Plan: Samples to be drawn from each roller as set for sealing at after machine setting , Beginning of filling,
Middle of filling and end of filling.

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 19 of 24
Title : Validation Protocol for B. No. :

Stage Volume measured in measuring Cylinder Appearance Inspected

by
1 2 3 4 5 6 7 8
After machine
setting
Beginning of
filling
Middle of
filling
End of filling

Conclusion:

Checked by: ___________________________ Date_________________________

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 20 of 24
Title : Validation Protocol for B. No. :

Data recording sheet V

Equipment Name: Monoblock filling & sealing machine
Identification no: ________________________________
Machine Speed:____________________
Procedure: Capped bottles to be checked for seal breaking and recapping.

Method reference: Leak test procedure for Capped bottles.

stage No of bottle Recapping Seal breaking No of Leakers

tested
After machine Setting
Beginning of Capping
Middle of Capping
At the end of Capping

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 21 of 24
Title : Validation Protocol for B. No. :

Data recording sheet VI

Equipment Name: Bottle labeling machine / Domino printing machine
Identification no: ________________________________
Machine Speed: ____________________
Procedure: Labeled bottles to be checked for clean, position of label and crossed label.

Method reference: Leak test procedure for Capped bottles.

stage No of bottle Clean Position of label Crossed label

tested
After machine Setting
Beginning of Capping
Middle of Capping
At the end of Capping

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 22 of 24
Title : Validation Protocol for B. No. :

Data recording sheet VII

Analysis Report
Product Name:
Batch No.: Batch size:
Mfg. Date: Exp. Date:
Composition:

Test method reference: In house

Sr. Test
Specification Results Remark
No.
01 Description
02 pH
03 Specific Gravity
04 Uniformity Of volume
05 Assay
5.1 % Labeled amount: 90 % - 110 %
Quantity Found:
5.2 % Labeled amount: 90 % - 110 %
Quantity Found:
5.3 % Labeled amount: 90 % - 110 %
Quantity Found:
5.4 % Labeled amount: 90 % - 110 %
Quantity Found:

Remark:
Result: The sample referred above complies / does not comply with the standard prescribed as per In house
Specification.
N.B. Calculation sheet attached

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 23 of 24
Title : Validation Protocol for B. No. :

Data recording sheet VIII

Sr Name of critical equipment / Utilities Qualification / Date of Qualification /

No Validation file Validation
reference No
1 S.S. Manufacturing tank
2 S.S. Storage vessel
3 Filter press
4 Transfer Pump
5 Washing Machine
6 Filling Machine
7 Sealing Machine
8 Labeling Machine

Utilities:
1 AHU System
2 Water System
3 Compressed Air
4 Steam
5 Lightning
6 Drain

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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 24 of 24
Title : Validation Protocol for B. No. :

Data recording sheet IX

Remark:
Analytical Method Validation protocol attached
Conclusion

Sr. Stage Acceptance criteria Observation

No.
1. Sugar Syrup Uniformity of sugar
Preparation
2. Manufacturing Complies as per BMR
3. Bottle No particulate matter observed
Washing
4. Filling and Volume shall be more than labeled
Sealing claim
5. Capping Leak test
6. Labelling and Crossed label shall not be more than 2
packing mm at the edge, label shall not be peeled
off after drying

Conclusion:
Product _________________________________ manufactured as per B.M.R. No _____________ meets
predefined acceptance criteria.

Analysis By Approved By

Date Date

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