1. Seminar
on
VALIDATION PROTOCOLS
GUIDED BY:
PRESENTEDE BY:
SAHILHUSEN I . JETHARA
M. PHARM – I (2013-14)
ROLL NO. - 02
Dr. M. R. PATEL
Principale & HOD in
pharmaceutics
DEPARTMENT OF PHARMACEUTICS
SHRI B. M. SHAH COLLEGE OF PHARMACEUTICAL EDUCATION AND
REASERCH, MODASA-2013
SHRI BMCPER, MODASA NIKITA
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2. LIST OF CONTENTS………
INTRODUCTION
TABLETS
PHARMACEUTICAL
ORAL
POWDERS
LIQUID
SEMISOLID
SHRI BMCPER, MODASA NIKITA
DOSAGE FORM
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3. INTRODUCTION
VALIDATION
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, &
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quality
4. 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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5. 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.
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6. TABLETS
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.
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7. Validation
IN CASE OF TABLETS IT IS DONE FOR:1.
2.
3.
4.
RAW MATERIAL
PROCESS
PRODUCT
FINISHED PRODUCT
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8.
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 compliance
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10. PRODUCT VALIDATION:1.
2.
3.
4.
5.
6.
Raw Material
Packaging Material
Granules
Compressed Tablets
Coated Tablets
Packed Final Product
FINISHED PRODUCT VALIDATION:1. ORGANOLEPTIC PROPERTY
2. PHYSICAL CHARACTERISTIC
3. CHEMICAL CHARACTERISTIC
4. BIOLOGICAL CHARACTERISTIC
5. MICROBIOLOGICAL CHARACTERISTIC
6. STABILITY TESTING
7. STORAGE CONDITION
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11. PHARMACEUTICAL
POWDERS
API +
EXCIPIENT
(BOTH ARE IN POWDERED FORM)
POWDER
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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SHRI BMCPER, MODASA NIKITA
12. POWDERS AS A PRIMARY
REQUIREMENT FOR DOSAGE FORM
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13. VALIDATION
1.
Validation of Raw material
2.
Validation of Blending Equipments
3.
Validation of Blending operation
4.
Validation of final packed material
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14. 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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15. 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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16. 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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17. 4. Validation of final packed
material
Checking integrity of foils
Checking integrity of sealing
Checking opening ease
Permeability of foils
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21. 1. Process Variables
Process
Equipments
Process variables
Mixing of
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.
liquid
Properties
affected by
variables
Appearance
of liquid,
Viscosity of
liquid.
Monitoring
output
Potency,
Appearance,
pH,
Viscosity,
Specific
gravity.
23. 2. PRODUCT VALIDATION
Major test parameters used for final product testing
Appearance
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
24. 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
29. ABC Pharmaceuticals.
27, Mahalaxmi Estate, Vatva, Ahmedabad.
5. Document required
Document
Effective Date
Ref. No.
MFR
BMR
BPR
Test data sheet
6. List of equipments
Prepared by
Checked by
31. ABC Pharmaceuticals.
27, Mahalaxmi Estate, Vatva, Ahmedabad.
8. Parameters to be tested
Process stage
1)
Mixing
Process variable
Validation response
Mixing time
Mixing rate
Mixing temp.
→By assay
→Consistency Test
Filling rate
Speed
→Weight variation
→Sealing temp.
→Pressure, Crimping
→Coding.
a)
b)
c)
2)
Filling
a)
b)
Prepared by
Checked by
32. ABC Pharmaceuticals.
27, Mahalaxmi Estate, Vatva, Ahmedabad.
9. Sampling plan
Process Stage
1) Mixing
No. of sample
taken
2
Qty of sample
taken
2)
Filling
Prepared by
Qty
Test
30 gm from
each location
Test
Equivalent to no
of filling station
Checked by
33. ABC Pharmaceuticals.
27, Mahalaxmi Estate, Vatva, Ahmedabad.
10. Acceptance criteria
Stage
Tests
1) Mixing
Assay of ingredients
Consistency test
2) Filling
Spread smoothly &
homogeneously
FOR 15 gm
Wt of empty tube
Wt of filled tube
Net content
Crimping
Coding
Sealing
Sealing temp.
Air trapping
Pressure
Assay of ingredients
Prepared by
Acceptance Criteria
Legible
Straight & Smooth
Complete & Leak proof
280°C – 300°C
Free from air bubble
3.5 – 4.0 Kg/cm2
Checked by
