2. VALIDATION
Documented program
Pre-determined specifications and quality attributes
WHO - Validation is documented act of providing that any procedure,
process, equipment, material, activity or system actually leads to the
expected results
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3. SCOPE OF VALIDATION
1. Instrument calibration
2. Process utility services (support services)
3. Raw materials and Packaging materials (Stage 1 & 2)
4. Equipment
5. Manufacturing
6. Product design
7. Cleaning
8. Operators (knowledge,
skills, attitude)
9. Analytical test methods
i. Accuracy
ii. Precision
a. Repeatability
b. Reproducibility
c. Intermediate precision
iii. Linearity
iv. Range
v. Limit of detection (LOD)
vi. Limit of quantification
(LOQ)
vii. Ruggedness
viii. RobustnessAasawaree Jeevan Yadav
4. 1. Manufacturing process control (raw material)
2. Pre-formulation evaluation
3. Stability studies
4. Environmental control/checks
5. Cleaning controls (contamination)
APPLICATIONS OF VALIDATION
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6. USFDA - establishing documented evidence which provides a
high degree of assurance that a specific process (such as the
manufacture of pharmaceutical dosage forms) will
consistently produce a product meeting its predetermined
specifications and quality characteristics.
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7. OBJECTIVE OF PROCESS VALIDATION
1. Reduces variation between various batches.
2. Assurance of quality of the product.
3. Decreases the risk of regulatory
noncompliance.
4. Ensure the consistency of the manufacturing
operation and reproducibility of the process.
5. Ensure the existence of all necessary quality assurance system within
organization.
6. More rapid and reliable start-up of new equipment.
7. Easier scale-up from development work.
8. Easier maintenance of equipment.
9. Improve employee awareness for processes.
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8. REASONS FOR PROCESS VALIDATION
Changes in:
1. New product or existing products as per
SUPAC (Scale-Up and Post Approval
Changes)
2. Site of manufacturing.
3. Batch size.
4. Equipment.
5. Process existing products.
6. Composition or components.
7. Critical control parameters.
8. Vendor of API or critical excipient.
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9. ADVANTAGES OF PROCESS VALIDATION
1. Simple process
2. Moisture sensitive and heat sensitive products
3. Consistent through output.
4. Reduction in rejections and reworks.
5. Fewer complaints about process related failure.
6. Reduced testing in process and finished goods.
7. Easier scale-up from development work.
8. Easier maintenance of equipment.
9. More rapid and accurate investigations process deviation.
10. Increased confidence about process reproducibility and product
quality.
11. Improve employee awareness of processes.
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10. STRATEGY FOR VALIDATION METHODS
1. Define the application purpose
and scope of the method
2. Define the performance
parameters and acceptance
criteria
3. Define validation experiments
4. Develop SOPs for executing the
method routinely
5. Define criteria for revalidation
6. Document validation
experiments and results in the
validation report
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12. PHASES OF PROCESS VALIDATION
1. Pre-validation Qualification
2. Process Validation
3. Validation Maintenance
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13. expected or expecting to be the
specified thing in the future
existing, happening, or done at the
same time
looking back on or dealing with
past events or situations
repetition of a validation process
TYPES OF PROCESS VALIDATION
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14. PRINCIPLES OF VALIDATION
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
CRITICAL FACTORS OF PROCESS VALIDATION
1. All the critical point of the process should be clearly identified.
2. The process should run using the extremes of the system at the
critical points.
3. The quality system should support the validation effort by way of
document control, preventive maintenance, calibration, etc.
4. Adequate data are required to provide statistical support to
demonstrate product consistency.
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15. 1. Validation Master Plan (VMP)
2. Validation Protocol (VP)
3. Validation Reports (VR)
4. Standard Operating Processes
(SOPs)
DOCUMENTATION IN VALIDATION PROCESS
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19. LIQUID DOSAGE FORMS CAN BE PREPARED
1. By dissolving the active drug substance(s) in an aqueous or
nonaqueous (e.g. alcohol, ether, glycerin) solvent
2. By suspending the drug in appropriate medium
3. By incorporating the drug substance into an oil or water phases
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20. MANUFACTURING OF MONOPHASIC LIQUIDS
Process Flow
Mixing
Addition of Raw
Materials
Active
Excipients
Mixing time
RPM
Temperature
Final volume
Measured ResponsesControl Variables
Clarity
Viscosity
Assay
ClarityMesh size
Filter integrity
Filtration
VolumeFilling machine speedFilling
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21. MANUFACTURING OF BIPHASIC LIQUIDS
Water
Continuous
Phase
Other
helping
agents
Mixing
Aqueous
solution
Dispersed
Phase
For
suspension
Preservatives
Surfactants
Drug solution
in oil
Grinding of
Drug and
other solids
Dissolved
drug in oil
For
emulsion
Milled
drug
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24. OBJECTIVES OF PROCESS VALIDATION FOR LIQUIDS
To do the process
systematically to assure the
quality of the product
Ensures that the product meet
the predetermined
specifications
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26. NUMBER OF VALIDATION TRIALS
For New Product, Product Transfer or Having Major Changes
generally at least three consecutive successful batches are required:
1. One Right = Accident
2. Two Right = Coincidence
3. Three Right = Validated
SAMPLING FOR VALIDATION
For Solution, take at least 2 samples at top and bottom of the bulk
For Suspension, take at least 2 samples at top, Middle and Bottom of
the bulk
Finished Product Testing (Net content, Microbiology, Content
Uniformity)
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27. CRITICAL PARAMETERS
Equipment
Mixing speed
Homogenizing speed
Mixing time
Heating/ cooling time
Flow rate
Manufacturing
Dissolving step
Melting step
Homogenizing step
Processing
Mixing speed
Mixing time
Cooling time
Homogenizing speed
Homogenizing timeAasawaree Jeevan Yadav
29. TEST PARAMETERS FOR SUSPENSIONS AND EMULSIONS
TEST PARAMETER SUSPENSION EMULSION
Appearance √ √
Viscosity √ √
pH √ √
Content uniformity √ √
Sedimentation √ ˟
Re-suspendability √ ˟
Particle size √ √
Release rate √ √Aasawaree Jeevan Yadav
30. OPERATIONS IN PROCESS VALIDATION
Raw material validation
1. Particle size and size distribution
2. Particle shape or morphology
3. Microbial count
4. pH of the solvent or vehicle
Monitoring outputs
1. Appearance
2. pH value and Viscosity
3. Microbial count
4. Content uniformity
5. Dissolution testing
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31. OPERATIONS IN PROCESS VALIDATION
Filling and Packaging
Operation Validation
1. Leakage test for filled
bottle
2. Cap sealing test
3. Fill volume
determination
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32. VALIDATION REPORT
Validation Team must prepare
the report
Report must be reviewed and
approved by QA.
Written Notification or either
successful completion or
failure of the process
validation must be issued to
top management.
In case of failure, an
investigation must be
completed and documented
prior to repeat the validation
study.
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33. CHANGES AND REVALIDATION
Change of any of the following may need revalidation
1. Formula Composition
2. Raw Material Source
3. Manufacturing Process
4. Manufacturing Location
5. Equipments
6. Batch Size
1. Minor
2. Intermediate
3. Major
CHANGES
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34. accurate and reliable method of
estimation
quality, identity, strength, purity,
stability, effectiveness and safety
better acceptability of the drug
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