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Protocol No.: Quality Assurance Department Title : Validation Protocol for Process Validation Protocol for Oral liquid/Suspension Page 1 of 24 B. No. :

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

Number of batches studied: First Three Batches Batch numbers: 1. 2. 3.

Validation activity Approved by: _____________________________Date:_______________________ Validation Team: Department Production Validation Team

Quality Control

Quality Assurance

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

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Process Validation Protocol for Oral liquid/Suspension 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

Personnel Responsibilities:

Sr No 1 2 3 4

Activity

Responsibility

Remarks

Preparation of validation protocol Review of validation report. Production of validation Batches Testing of validation samples & Preparation of validation report

QA Department Q.A In charge Production In charge Q.C In charge

Approval of Validation protocol

Manager (Q.A)

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Protocol No.: Quality Assurance Department Title : Validation Protocol for 3.0 Process Description / Flow Sheet Process Validation Protocol for Oral liquid/Suspension Page 3 of 24 B. No. :

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.

DISPENSING OF MATERIAL

SUGAR SYRUP PREPARATION

BULK MANUFACTURING

PH ADJUSTMENT

VOLUME MAKE UP

FILTRATION

WASHING, FILLING AND SEALING

3.1

Formulation: Batch Size:

Sr No 1 2 3 4 5

Ingredients/Excipients

Unit per ml

Quantity in Kgs

Overages

Quantity with Overages

Dispensed Function Quantity

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Protocol No.: Quality Assurance Department Title : Validation Protocol for 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Note: Process Validation Protocol for Oral liquid/Suspension Page 4 of 24 B. No. :

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Protocol No.: Quality Assurance Department Title : Validation Protocol for 3.2 FLOW SHEET: MANUFACTURING PROCESS DIAGRAM:- _________________syrup Process Validation Protocol for Oral liquid/Suspension Page 5 of 24 B. No. :

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

Filling Of Bulk Into Bottles

Inspection

Testing

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Process Validation Protocol for Oral liquid/Suspension Page 6 of 24 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 SrNo 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 List of SOPS, Validation & Qualification report used as references Equipment Equipment No. SOP No

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

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

Remarks:

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Protocol No.: Quality Assurance Department Title : Validation Protocol for 4.3 Identification of Critical process variables parameter. Process Validation Protocol for Oral liquid/Suspension Page 9 of 24 B. No. :

4.3.1 Probable causes that may effect final product:

DISPENSING OF MATERIAL SUGAR SYRUP PREPARATION ADDITION OF ACTIVE ADDITION OF FLAVOUR & COLOUR WASHING, FILLING & SEALING

LOAD SIZE SPEED

ACTIVE

FINAL WASH STIRRER

CLARITY

PH & TEMP. EXCIPIENT R.P.M. MIXING TIME

VOLUME

CLARITY MIXING TIME

LEAKAGE SEALING & THRADING

R.P.M.

R.P.M. DIP STICK

T E M P.

MIXING TIME

PH SCREEN SIZE VOLUME

ADDITION OF EXCIPEINT

pH ADJUSTMENT

VOLUME MAKEUP & FINAL MIXING

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

Critical Process PARAMETERS:

Sr No

Critical process variable Sugar Syrup Preparation

Response parameter

Remarks

Mixing time Load charge in to a Blender Uniformity of sugar

Fixed speed.

Fixed batch size

Final mixing and volume make up 2 Mixing time Load charge in to a Blender

Uniformity of Active Drugs

Fixed speed.

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

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

Sr No 1

Process / Variable

Machine setting ( Control Variables) Mixing Time Temperature Mixing Time

Remarks

Sugar syrup preparation Manufacturing

Load time Mixing time Bottle washing

3 4

Washing Pressure

Bottle filling & Sealing

Adjustment Of Volume

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Process Validation Protocol for Oral liquid/Suspension 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 Total samples:________ ____________minutes A,B & C ________ minutes A,B & C

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Protocol No.: Quality Assurance Department Title : Validation Protocol for 5.2 Sampling: Process Validation Protocol for Oral liquid/Suspension Page 13 of 24 B. No. :

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

Sampling thief As specified in the BMR Ref. std. : As specified in the BMR As per standard testing procedure

Assay

Assay 90 % to 110 %

Bottle washing

Visual inspection

inspected for particulate matter

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

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Protocol No.: Quality Assurance Department Title : Validation Protocol for 6.0 Recording of data & Data treatment: 6.1 Data Recording: Process Validation Protocol for Oral liquid/Suspension Page 14 of 24 B. No. :

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 Sheet No 2 Sheet No 3 Sheet No 4 Sheet No 5 Sheet No 6 Sheet No 7 Sheet No 8 Sheet No 9 For recording sugar syrup preparation & results For recording of bulk manufacturing and results For recording of bottle washing and results For recording of bottle filling and sealing For recording of capping For recording of labeling and packing For recording of analysis report For recording general utilities /equipment / method qualitical /results. For recording analytical method validation.

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Data recording sheet no I Sugar syrup preparation: Equipment name Identification no Capacity :_______________________ :_______________________ : ______________________lt. Date:____________________ Process Validation Protocol for Oral liquid/Suspension Page 15 of 24 B. No. :

Ingredients and sequence of material addition: ____________________ Total Volume of ingredients : _______________ltr. Mixing time Setting stirrer Procedure Plan locations For Sugar syrup preparation: Result after mixing _________________ minutes Points Sample A Sample B Sample C Temperature Clarity Weight per ml : _______ minutes : slow : As outlined in the batch manufacturing record. : Samples to be drawn at of ___ minutes of mixing from 3 x 100 ml different

Analyst:

Date

Conclusions:

Checked By: _________________________

Date: ____________________

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Data recording sheet no II Manufacturing (Manufacturing Tank): Equipment Name Identification no Capacity :_________________________ :_________________________ : ______________________lt. Date:___________________ Process Validation Protocol for Oral liquid/Suspension Page 16 of 24 B. No. :

Ingredients and sequence of material addition: ____________________ Total weight of ingredients Mixing time Setting stirrer Procedure Plan : _______________ltr. : ______ minutes : slow : As outlined in the batch manufacturing record. : 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 Between to Top Middle Bottom Mean Standard Deviation % Relative standard deviation Weight per ml Between to Identification Assay 90 to 110%

N.B. Calculation sheet attached

Assay of after mixing ____________ minutes Prepared By Checked By Approved By

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Location Appearance pH Between to Top Middle Bottom Mean Standard Deviation % Relative standard deviation Weight per ml Between to Process Validation Protocol for Oral liquid/Suspension Page 17 of 24 B. No. : Identification Assay 90 to 110%

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

N.B. Calculation sheet attached Conclusion:

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Data recording sheet III Equipment Name: Bottle washing Machine Identification no Capacity :_________________________ Date:___________________ Process Validation Protocol for Oral liquid/Suspension Page 18 of 24 B. No. :

: ______________________ (Bottle per minutes)

Method reference: Visual inspection. Observation : Washed bottle shall be inspected for particulate matter. Stage Inspected by After setting Beginning washing Middle washing End of washing of of machine 1 2 3 4 5 6 7 8 9 10

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.: Quality Assurance Department Title : Validation Protocol for Stage Volume measured in measuring Cylinder Process Validation Protocol for Oral liquid/Suspension Page 19 of 24 B. No. : Appearance Inspected by 1 After machine setting Beginning of filling Middle filling End of filling Conclusion: of 2 3 4 5 6 7 8

Checked by: ___________________________

Date_________________________

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

Data recording sheet VII Analysis Report Product Name: Batch No.: Mfg. Date: Composition: Test method reference: In house Sr. No. 01 02 03 04 05 5.1 Description pH Specific Gravity Uniformity Of volume Assay % 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: Test Specification Results Remark Batch size: Exp. Date:

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

Sr No

Name of critical equipment / Utilities

Qualification / Validation file reference No

Date of Qualification / Validation

1 2 3 4 5 6 7 8

S.S. Manufacturing tank S.S. Storage vessel Filter press Transfer Pump Washing Machine Filling Machine Sealing Machine Labeling Machine

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

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Protocol No.: Quality Assurance Department Title : Validation Protocol for Data recording sheet IX Remark: Analytical Method Validation protocol attached Conclusion Sr. No. 1. Sugar Syrup Preparation 2. 3. Manufacturing Bottle Washing 4. Filling and Sealing 5. 6. Capping Volume shall be more than labeled claim Leak test Complies as per BMR No particulate matter observed Uniformity of sugar Stage Acceptance criteria Observation Process Validation Protocol for Oral liquid/Suspension Page 24 of 24 B. No. :

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 Date

Approved By Date

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