Reason for Performing the Validity Study
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XXXXXXXXXXXXXXXXXXXXXXX Protocol No.: Process Validation Protocol for Oral liquid/Suspension Quality Assurance Department Page 1 of 22 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
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
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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)
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
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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 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
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22
Note:
3.2 FLOW SHEET: MANUFACTURING PROCESS DIAGRAM:- ______syrup
Receipt and holding Dispensing Of Raw of materials Material
SyrupExcipient Preparation and active addition
Colour & Flavour Materials
Bulk Preparation & Final Volume Make up Approved By Prepared By Checked By Cleaning And Setting Of Filling, Sealing, Labeling FiltrationFilling ThroughFinal Of Mixing Bulk Filter Press Inspection Testing Machine Into Bottles XXXXXXXXXXXXXXXXXXXXXXX Protocol No.: Process Validation Protocol for Oral liquid/Suspension Quality Assurance Department Page 5 of 22 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
4.2 Details of equipment to be used.
Equipment Details S.S. Manufacturing Tank Type : Model:
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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 : Model: Capacity: Manufacturer: Tag No. Speed M.O.C. Filling Machine Type :
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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:
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 SEALING & CLARITY THRADING Approved By Prepared By Checked By XXXXXXXXXXXXXXXXXXXXXXX Protocol No.: Process Validation Protocol for Oral liquid/Suspension Quality Assurance Department Page 8 of 22 Title : Validation Protocol for B. No. :
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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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. Fixed temperature for washing D.M. Water pressure Fixed pressure of air D.M. Water temperature Cleaning Of Bottle Fixed cycle 3 Compressed air pressure Washing efficiency Fixed direction Washing cycle Alignment & blockage of needles Filling & Sealing Fixed speed Volume variation 4 Speed of filling machine Volume Uniformity Leakage Leak test Clean, Position & Clean Label 5 Labeling & Packing Proper Sealing Position Sealing
Sr Machine setting Process / Variable Remarks No ( Control Variables) Approved By Prepared By Checked By XXXXXXXXXXXXXXXXXXXXXXX Protocol No.: Process Validation Protocol for Oral liquid/Suspension Quality Assurance Department Page 10 of 22 Title : Validation Protocol for B. No. :
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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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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5.2 Sampling:
Stage / Test Parameter Equipment Acceptance Criteria (Size, Location & Time) Sugar syrup Preparation Determination on each sample, for Not more than ______minutes temperature, & Clarity 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
6.0 Recording of data & Data treatment: 6.1 Data Recording:
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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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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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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 Location Appearance pH Weight per ml Identification Assay Between Between 90 to 110% to to Approved By Prepared By Checked By XXXXXXXXXXXXXXXXXXXXXXX Protocol No.: Process Validation Protocol for Oral liquid/Suspension Quality Assurance Department Page 16 of 22 Title : Validation Protocol for B. No. :
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:
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 Approved By Prepared By Checked By XXXXXXXXXXXXXXXXXXXXXXX Protocol No.: Process Validation Protocol for Oral liquid/Suspension Quality Assurance Department Page 17 of 22 Title : Validation Protocol for B. No. :
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.
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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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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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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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
Data recording sheet VIII
Sr Name of critical equipment / Utilities Qualification / Date of Qualification / No Validation file Validation
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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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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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