Process Validation of Liquid

XXXXXXXXXXXXXXXXXXXXXXX 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

Prepared By

Checked By

Approved By




Page 2 of 24


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

Sr

Personnel Responsibilities:

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

Prepared By

Manager (Q.A)

Checked By

Approved By




Page 3 of 24

Title : Validation Protocol for 3.0

B. No. :

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 Function Quantity

1 2 3 4 5

Prepared By

Checked By

Approved By




Page 4 of 24


B. No. :

6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Note:

Prepared By

Checked By

Approved By




Page 5 of 24


B. No. :

3.2 FLOW SHEET: MANUFACTURING PROCESS DIAGRAM:- _________________syrup

Receipt and holding of materials

Dispensing Of Raw 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, Sealing, Labeling Machine

Prepared By

Filling Of Bulk Into Bottles

Checked By

Inspection

Approved By

Testing




Page 6 of 24


4.0

B. No. :

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 1

Equipment

Equipment No.

SOP No

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Prepared By

Checked By

Approved By




Page 7 of 24


B. No. :

4.2 Details of equipment to be used. Equipment S.S. Manufacturing Tank

Details 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.

Washing Machine

Prepared By

M.O.C. Type :

Checked By

Approved By




Page 8 of 24


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:

Prepared By

Checked By

Approved By




Page 9 of 24


B. No. :

Identification of Critical process variables parameter.

4.3.1 Probable causes that may effect final product: DISPENSING OF MATERIAL

SUGAR SYRUP PREPARATION

ADDITION OF ACTIVE

WASHING, FILLING & SEALING

ADDITION OF FLAVOUR & COLOUR

LOAD SIZE SPEED

FINAL WASH

ACTIVE

STIRRER

CLARITY

PH & TEMP. R.P.M.

EXCIPIENT

VOLUME

MIXING TIME

LEAKAGE SEALING & THRADING

CLARITY MIXING TIME

R.P.M.

R.P.M.

DIP STICK

T E M P.

ADDITION OF EXCIPEINT

Prepared By

PH

MIXING TIME

SCREEN SIZE

pH ADJUSTMENT

Checked By

VOLUME

VOLUME MAKEUP & FINAL MIXING

Approved By




Page 10 of 24


B. No. :

Critical Process PARAMETERS:

Sr No

Critical process variable

Response parameter

Sugar Syrup Preparation 1

Final mixing and volume make up 2

Fixed speed.

Mixing time Load charge in to a Blender

Mixing time Load charge in to a Blender

Remarks

Uniformity of sugar

Uniformity of Active Drugs

Fixed batch size

Fixed speed.

Fixed batch size Washing

Fixed pressure for washing.

D.M. Water pressure

Fixed temperature for washing

D.M. Water temperature

Cleaning Of Bottle

3

Fixed pressure of air Fixed cycle

Compressed air pressure

Washing efficiency

Washing cycle

Fixed direction

Alignment & blockage of needles Fixed speed

Filling & Sealing 4

Speed of filling machine Leak test

5

Labeling & Packing

Volume Uniformity

Volume variation Leakage

Clean, Position &

Clean Label

Proper Sealing

Position Sealing

Prepared By

Checked By

Approved By




Page 11 of 24


Sr

Sugar syrup preparation Manufacturing

2

Machine setting

Process / Variable

No 1

B. No. :

Load time

( Control Variables)

Remarks

Mixing Time Temperature Mixing Time

Mixing time

3 4

Bottle washing

Washing Pressure

Bottle filling & Sealing

Adjustment Of Volume

Prepared By

Checked By

Approved By




Page 12 of 24


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

Checked By

Approved By

Total samples:________

Prepared By




Page 13 of 24


B. No. :

Sampling:

Stage / Test Parameter

Equipment

Acceptance Criteria

(Size, Location & Time) Sugar syrup Preparation

Manufacturing

Determination on each sample, for

Not more than ______

temperature, & Clarity

minutes

Sampling thief

Appearance

As specified in the BMR

pH

Ref. std. :

weight per ml


Identification

As per standard testing procedure Assay 90 % to 110 %

Assay

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


Colour

Visual inspection


Capping

Leak test

Complies leak test

Cap breaking and recapping Labeling & Packing

Prepared By

Clean, Position & Proper Sealing

Clean label and proper sealing

Checked By

Approved By




Page 14 of 24


B. No. :

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.

Prepared By

Checked By

Approved By




Page 15 of 24


B. No. : Data recording sheet no I

Sugar syrup preparation: Equipment name

:_______________________

Identification no

:_______________________

Capacity

: ______________________lt.

Date:____________________

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 Temperature

Points

Clarity

Weight per ml

Sample A Sample B Sample C

Analyst:

Date

Conclusions:

Checked By: _________________________

Prepared By

Date: ____________________

Checked By

Approved By




Page 16 of 24


B. No. : Data recording sheet no II

Manufacturing (Manufacturing Tank): Equipment Name

:_________________________

Identification no

:_________________________

Capacity

: ______________________lt.

Date:___________________

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

Between

Between

to

to

Identification

Assay 90 to 110%

Top Middle Bottom Mean Standard Deviation % Relative standard deviation

N.B. Calculation sheet attached

Assay of after mixing ____________ minutes Prepared By

Checked By

Approved By




Page 17 of 24

Title : Validation Protocol for Location

B. No. :

Appearance

pH

Weight per ml

Between

Between

to

to

Identification

Assay 90 to 110%


N.B. Calculation sheet attached Assay of after mixing ____________ minutes Location

Appearance

pH

Weight per ml

Between

Between

to

to

Identification

Assay 90 to 110%


N.B. Calculation sheet attached Conclusion:

Prepared By

Checked By

Approved By




Page 18 of 24


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

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.

Prepared By

Checked By

Approved By

10




Page 19 of 24

Title : Validation Protocol for Stage

B. No. :

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: ___________________________

Prepared By

Checked By

Date_________________________

Approved By




Page 20 of 24


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

Prepared By

Checked By

Approved By




Page 21 of 24


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

Prepared By

Checked By

Approved By




Page 22 of 24


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

No. 01

Description

02

pH

03

Specific Gravity

04

Uniformity Of volume

05

Assay

5.1

Results

Remark

% Labeled amount: 90 % - 110 % Quantity Found:

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. N.B. Calculation sheet attached

Prepared By

Checked By

Approved By




Page 23 of 24


B. No. : Data recording sheet VIII

Sr

Name of critical equipment / Utilities

No

Qualification /

Date of Qualification /

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

Prepared By

Checked By

Approved By




Page 24 of 24


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

Prepared By

Checked By

Approved By

Process Validation of Liquid

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