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
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
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
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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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
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
Prepared By Checked By Approved By 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 :
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:
Prepared By Checked By Approved By EXCIPIENT ACTIVE LOAD SIZE T E M P. 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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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
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
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
Prepared By Checked By Approved By 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
Prepared By Checked By Approved By 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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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:
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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 to Between to 90 to 110% Top Middle Bottom Mean Standard Deviation % Relative standard deviation
N.B. Calculation sheet attached
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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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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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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:
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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
Prepared By Checked By Approved By
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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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.
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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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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