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SHRI BMCPER, MODASA NIKITA 11
Seminar on
VALIDATION PROTOCOLS
DEPARTMENT OF PHARMACEUTICSSHRI B. M. SHAH COLLEGE OF PHARMACEUTICAL EDUCATION AND
REASERCH, MODASA-2013
GUIDED BY: Dr. M. R. PATELPrincipale & HOD in pharmaceutics
PRESENTEDE BY:
SAHILHUSEN I . JETHARAM. PHARM – I (2013-14)ROLL NO. - 02
SHRI BMCPER, MODASA NIKITA2
LIST OF CONTENTS………
INTRODUCTION TABLETSPHARMACEUTICAL POWDERSORAL LIQUID SEMISOLID DOSAGE FORM
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INTRODUCTIONVALIDATION
It is a documented programme which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications & quality attributes.
Why validation is required? Manufacturers require by law to conform to cGMP. To avoid possibility of rejected or recalled batches.
- To ensure the product uniformity , reproducibility, &
quality
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Validation Protocol
It gives Details of the critical parts of the of the
manufacturing process. Information about the key parameters that are
to be measured. Allowable range of variability in case of
measured parameters. The manner in which the system will be tested.
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Types of validation Prospective Validation:- an experimental protocol is
run before starting of actual use. Concurrent Validation:-In process monitoring of critical
processing steps & end product testing of current production
Retrospective Validation:-It is chosen for established products where their manufacturing processes are considered to be stable ( i.e. long history state of control)
Validation is done for.:- a) Raw materials
b) Process
c) Product.
TABLETS
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It is unit solid dosage forms containing drug substances with or without suitable diluents and prepared by compressing powdered or granulated medicinal substances in die.
Validation
IN CASE OF TABLETS IT IS DONE FOR:-
1. RAW MATERIAL
2. PROCESS
3. PRODUCT
4. FINISHED PRODUCT
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RAW MATERIAL VALIDATION:- Raw material is validated for particle size, surface area,
particle size distribution, colour , Appearance, texture, density, flowability , compressibility etc
PROCESS VALIDATION:-
Two stage First identify the critical process parameter and design
protocol Manufacture three batches of product controlling the
critical parameter and test it for complianceSHRI BMCPER, MODASA NIKITA
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PRODUCT VALIDATION:-
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1. Raw Material2. Packaging Material3. Granules 4. Compressed Tablets5. Coated Tablets6. Packed Final Product
FINISHED PRODUCT VALIDATION:-1. ORGANOLEPTIC PROPERTY2. PHYSICAL CHARACTERISTIC3. CHEMICAL CHARACTERISTIC4. BIOLOGICAL CHARACTERISTIC5. MICROBIOLOGICAL CHARACTERISTIC6. STABILITY TESTING7. STORAGE CONDITION
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PHARMACEUTICAL POWDERS
API + EXCIPIENT POWDER (BOTH ARE IN POWDERED FORM) DOSAGE FORM
Powder are homogeneous mixture of drug/drugs and excipient/excipients in a dry, fine state of subdivision.
It is important to note that term" POWDER” is restricted only to “POWDERS FOR INTERNAL USE ONLY”.
But not used for other powder mixtures. For EX. like powder for external use they rather called as “Dusting powders”.
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POWDERS AS A PRIMARY REQUIREMENT FOR DOSAGE FORM
VALIDATION1. Validation of Raw material
2. Validation of Blending Equipments
3. Validation of Blending operation
4. Validation of final packed material
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1. VALIDATION OF RAW MATERIAL
Physical characteristics of raw material can vary among manufacturers of drug substances.
Inspection should cover the firm’s data for the specification for drug substances.
RAW MATERIAL SPECIFICATION Description, identification, melting range, ph, water,
residue on ignition, chloride, sulfate, sulfide, heavy metals, readily carbonizable substances, total aerobic microbial count, mould and yeast count, E. Coli, acceptable container, approved expiry date, approved suppliers.
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2. VALIDATION OF BLENDING EQUIPMENTS
What is the working capacity of equipment? Does the equipment operate more efficiently with the density
of fluffy powders? What is the working load range, i.e. the proper blender load to
ensure good uniformity of blend? What feature does the equipment have for ease of handling of
powders, automated charging and discharging Can the equipment heat the powder blend if needed for
application as a dryer as well as a granulator? Is the method of heating electric or steam?
May a vacuum be used with the equipment? Does the equipment have the capacity to wet the powder
blend?
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3. Validation of Blending
operation
Determination of the optimum blending time De-mixing or segregation Verification of homogeneity of mixed powders Interaction between process & material Validation of characteristics of blend. -Bulk density -Particle size distribution -Moisture content Load size in blending apparatus Powder flow
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4. Validation of final packed material
Checking integrity of foils
Checking integrity of sealing
Checking opening ease
Permeability of foils
Classification
1. PROCESS VARIABLES
2. PRODUCT VALIDATION
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1. Process VariablesProcess Equipme-
ntsProcess variables Properties
affected by variables
Monitoring output
Mixing of
liquid
Kettle & Tank fitted with agitator
Capacity of unit,
Shape & position
of agitation system,
Order of addition,
Rate of addition,
Fill volume,
Mixing speed of agitator,
Temperature of liquid,
Mixing time.
Appearance of liquid, Viscosity of liquid.
Potency, Appearance, pH,
Viscosity, Specific gravity.
Process Equipment Process variables
Properties affected by variables
Monitoring output
Dispersing Homogenizer, Colloid mill, ultrasonic device
Bore opening/
clearance of rotor & stator/power setting,
Pressure/rotor speed/power consumption,
Feed rate,
Temperature,
Dispersion time,
Order of mixing.
Particle size of solids,
Viscosity of liquid.
Potency,
Particle size
Distribution,
Viscosity,
Specific gravity.
2. PRODUCT VALIDATION
Major test parameters used for final product testingAppearance
pH
Viscosity
Specific gravity
Microbial count
Leakage test for filled bottle (By plastic vacuum dessicator)
Check the cap sealing
Fill volume determination
Particulate matter testing
Water vapour permeability test
Stress test
Test parameters specific for suspension • Sedimentation rate• Resuspendibility• Particle size & particle size distribution• Zeta potential measurement
Type of emulsion determination by• Dilution test • Conductivity test• Dye solubility test• COCl2 filter paper• Fluorescence test• Direction of creaming
Test parameters specific for solution • Clarity of solution• Color of solution
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Semisolid Dosage Form
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Process validation protocol
Contents
1. Protocol Approval2. Objective3. Scope4. Validation Approach5. Document Required 6. List of Equipments7. Product Detailed8. Parameter to be tested9. Sampling plan10. Acceptance Criteria
NameName DesignationDesignation SignatureSignature
Prepared ByPrepared By
Checked ByChecked By
Approved ByApproved By
ABC Pharmaceuticals.27, Mahalaxmi Estate, Vatva, Ahmedabad.
Prepared by Checked by
ABC Pharmaceuticals.27, Mahalaxmi Estate, Vatva, Ahmedabad.
5. Document required DocumentDocument Effective Date Effective Date Ref. No.Ref. No.
MFRMFR
BMRBMR
BPRBPR
Test data sheetTest data sheet
6. List of equipments
7. Product detailed
Generic name: Brand name: Product description: Dosage form: Labeled claim: Category: Composition with specification:
Prepared by Checked by
ABC Pharmaceuticals.27, Mahalaxmi Estate, Vatva, Ahmedabad.
8. Parameters to be tested
ABC Pharmaceuticals.27, Mahalaxmi Estate, Vatva, Ahmedabad.
Prepared by Checked by
Process stageProcess stage Process variableProcess variable Validation responseValidation response
1)1) MixingMixing a)a) Mixing timeMixing time
b)b) Mixing rateMixing rate
c)c) Mixing temp.Mixing temp.
→→By assayBy assay
→→Consistency TestConsistency Test
2)2) FillingFilling a)a) Filling rateFilling rate
b)b) SpeedSpeed
→→Weight variationWeight variation
→→Sealing temp.Sealing temp.
→→Pressure, CrimpingPressure, Crimping
→→Coding.Coding.
9. Sampling plan
ABC Pharmaceuticals.27, Mahalaxmi Estate, Vatva, Ahmedabad.
Prepared by Checked by
Process StageProcess Stage No. of sample No. of sample takentaken
Qty Qty TestTest
1) Mixing1) Mixing 22 30 gm from 30 gm from each locationeach location
Qty of sample Qty of sample takentaken
TestTest
2) Filling2) Filling Equivalent to no Equivalent to no of filling stationof filling station
10. Acceptance criteria
ABC Pharmaceuticals.27, Mahalaxmi Estate, Vatva, Ahmedabad.
Prepared by Checked by
StageStage TestsTests Acceptance CriteriaAcceptance Criteria
1) Mixing1) Mixing Assay of ingredientsAssay of ingredients
Consistency testConsistency test Spread smoothly & Spread smoothly & homogeneouslyhomogeneously
2) Filling2) Filling FOR FOR 15 gm15 gm
Wt of empty tubeWt of empty tube
Wt of filled tubeWt of filled tube
Net contentNet content
Crimping Crimping
CodingCoding
Sealing Sealing
Sealing temp.Sealing temp.
Air trappingAir trapping
Pressure Pressure
Assay of ingredientsAssay of ingredients
LegibleLegible
Straight & SmoothStraight & Smooth
Complete & Leak proofComplete & Leak proof
280280°°C – 300C – 300°°CC
Free from air bubbleFree from air bubble
3.5 – 4.0 Kg/cm3.5 – 4.0 Kg/cm22
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REFERENCES
Pharmaceutical process validation by Loftus and.Nash
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Ph. No. :- +918460378336Address:- 44, Assiyana Society; Dugarvada Road, Taluko & City : Modasa State: Gujarat Country: IndiaEmail: [email protected]
BEST OF LUCK TO ALL . . . . . . . . . .
SHRI BMCPER, MODASA NIKITA 36