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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
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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. :
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 :
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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. :
Prepared By Checked By Approved By
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. :
Prepared By Checked By Approved By
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. :
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
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. :
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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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 15 of 24
Title : Validation Protocol for B. No. :
Prepared By Checked By Approved By
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. :
Prepared By Checked By Approved By
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. :
Prepared By Checked By Approved By
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. :
Prepared By Checked By Approved By
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. :
Prepared By Checked By Approved By
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. :
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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Protocol No.: Process Validation Protocol for Oral liquid/Suspension
Quality Assurance Department Page 22 of 24
Title : Validation Protocol for B. No. :
Prepared By Checked By Approved By
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. :
Prepared By Checked By Approved By
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