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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. :

Prepared By Checked By Approved By

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. :

Prepared By Checked By Approved By

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

No

Activity Responsibility Remarks

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 &

Preparation of validation report

Q.C In charge

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. :

Prepared By Checked By Approved By

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

No

Ingredients/Excipients Unit per

ml

Quantity

in Kgs

Overages Quantity

with

Overages

Dispensed

Quantity

Function

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. :

Prepared By Checked By Approved By

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

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. :

Prepared By Checked By Approved By

3.2 FLOW SHEET:

MANUFACTURING PROCESS DIAGRAM:- _________________syrup

Receipt and holding of materials

Dispensing Of Raw Material

Final Mixing

Cleaning And Setting Of Filling, Sealing, Labeling Machine

Filling Of Bulk Into Bottles

Inspection Testing

Syrup Preparation Excipient and active addition

Colour & Flavour Materials

Bulk Preparation & Final Volume Make up

Filtration Through Filter Press

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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. :

Prepared By Checked By Approved By

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. :

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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. :

Prepared By Checked By Approved By

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. :

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EXCIPIENT

ACTIVE

LOAD SIZE

TEMP.

R.P.M.

PH

R.P.M.

DIP STICK

LEAKAGE SEALING & THRADING

CLARITY

4.3 Identification of Critical process variables parameter.

4.3.1 Probable causes that may effect final product:

ADDITION OF EXCIPEINT

STIRRER

SPEED

PH & TEMP.

R.P.M.

MIXING TIME

CLARITY

MIXING TIME

MIXING TIME

SCREEN SIZE VOLUME

FINAL WASH

VOLUME

DISPENSING OF

MATERIAL

SUGAR SYRUP

PREPARATION

ADDITION OF

ACTIVE

ADDITION OF

FLAVOUR &

COLOUR

WASHING,

FILLING &

SEALING

pH ADJUSTMENT VOLUME MAKEUP & 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. :

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Critical Process PARAMETERS:

Sr

No Critical process variable Response parameter Remarks

1

Sugar Syrup Preparation

Mixing time

Load charge in to a Blender

Uniformity of sugar

Fixed speed.

Fixed batch size

2

Final mixing and volume make up

Mixing time

Load charge in to a Blender

Uniformity of Active

Drugs

Fixed speed.

Fixed batch size

3

Washing

D.M. Water pressure

D.M. Water temperature

Compressed air pressure

Washing cycle

Alignment & blockage of needles

Cleaning Of Bottle

Washing efficiency

Fixed pressure for washing.

Fixed temperature for washing

Fixed pressure of air

Fixed cycle

Fixed direction

4

Filling & Sealing

Speed of filling machine

Leak test

Volume Uniformity

Fixed speed

Volume variation

Leakage

5 Labeling & Packing

Clean, Position &

Proper Sealing

Clean Label

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. :

Prepared By Checked By Approved By

Sr

No Process / Variable

Machine setting

( Control Variables) Remarks

1 Sugar syrup preparation Mixing Time

Temperature

2

Manufacturing

Load time

Mixing time

Mixing Time

3 Bottle washing Washing Pressure

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. :

Prepared By Checked By Approved By

5.0 Sampling, Test Parameters, Acceptance criteria

5.1 Sampling locations:

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:________

1. TOP –SAMPLE A

2. MIDDLE –SAMPLE B

3. BOTTAM –SAMPLE C

BOTTOM VALVE

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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. :

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5.2 Sampling:

Stage / Test Parameter Equipment

(Size, Location & Time)

Acceptance Criteria

Sugar syrup Preparation Determination on each sample, for

temperature, & Clarity

Not more than ______

minutes

Manufacturing

Appearance

pH

weight per ml

Identification

Assay

Sampling thief

� As specified in the BMR

� Ref. std. :

� As specified in the BMR

� As per standard testing

procedure

� Assay 90 % to 110 %

Bottle washing Visual inspection inspected for particulate

matter

Filling & sealing

Volume

Appearance

Odour

Colour

Measuring cylinder

Visual inspection,

Visual inspection

Visual inspection

Not less than label claim.

As specified in the BMR.

As specified in the BMR

As specified in the BMR

Capping Leak test

Cap breaking and recapping

Complies leak test

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. :

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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. :

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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. :

Prepared By Checked By Approved By

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

to

Between

to

90 to 110%

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. :

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Location Appearance pH Weight per ml Identification Assay

Between

to

Between

to

90 to 110%

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

to

Between

to

90 to 110%

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. :

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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

by

1 2 3 4 5 6 7 8 9 10

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. :

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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. :

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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

tested

Recapping Seal breaking No of Leakers

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. :

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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

tested

Clean Position of label Crossed label

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. :

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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 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. :

Prepared By Checked By Approved By

Data recording sheet VIII

Sr

No

Name of critical equipment / Utilities Qualification /

Validation file

reference No

Date of Qualification /

Validation

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. :

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Data recording sheet IX

Remark:

Analytical Method Validation protocol attached

Conclusion

Sr.

No.

Stage Acceptance criteria Observation

1. Sugar Syrup

Preparation

Uniformity of sugar

2. Manufacturing Complies as per BMR

3. Bottle

Washing

No particulate matter observed

4. Filling and

Sealing

Volume shall be more than labeled

claim

5. Capping Leak test

6. Labelling and

packing

Crossed label shall not be more than 2

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