Process Validation - Pharma Industry
Process Validation - Pharma Industry
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Presentation
1. Introduction
2. Technology Transfer
3. Process Validation
4. Manufacturing Optimization
5. Developed Work: Production of Injectables for Submission
6. Conclusions and Future Work
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1. Introduction
OBJECTIVES
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2. Technology Transfer
DEFINITION AND CLASSIFICATION
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2. Technology Transfer
ADVANTAGES AND OBSTACLES
Barriers:
Solutions:
Low government funding;
Political stability;
High cost for pre-qualification;
Flexibility.
Restrictions on technology exportation.
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3. Process Validation
DEFINITION AND STAGES
“Documented evidence with high degree of assurance that a process, operated within established
parameters, can perform effectively and reproducibly to produce a medicinal product meeting its
predetermined specifications and quality attributes” (World Health Organization)
Continued Process
Process Design Process Qualification Verification
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3. Process Validation
ADVANTAGES AND OBSTACLES
Barriers:
High costs to complete all stages; Solutions:
Extensive regulatory approvals; 21st century approach: wider
Lack of flexibility for alterations. lifecycle knowledge and flexibility
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4. Manufacturing Optimization
RISK ASSESSMENT
“Identification of hazards and evaluation of risks associated with exposure to those hazards.”
(ICH Q9)
Applicable to
Technology Transfer Scale-up between
between laboratory, pilot
manufacturing sites Manufacturing and production
processes
Probability
Potential Effect
Severity
Critical
Process Failure Cause Criticality
Parameters Detectability
Control
Risk Priority Number
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4. Manufacturing Optimization
PROCESS ANALYTICAL TECHNOLOGY (PAT)
Monitoring of Critical Process Parameters which affect the Critical Quality Attributes
In-line On-line
Continuous
Near-infrared spectroscopy
Biosensors
Improvement
Raman spectroscopy
Fiber optics
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5. Developed Work
Production of Injectables for Submission
INDUSTRIAL FACILITY AND PRODUCTION LINES
Hikma 1 Hikma 2
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5. Developed Work
Production of Injectables for Submission
PRODUCTION LINE 5
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5. Developed Work
Production of Injectables for Submission
STAGES
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5. Developed Work
Production of Injectables for Submission
PRODUCT A VALIDATION - DESCRIPTION
Injectable for the treatment of heart complications
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5. Developed Work
Production of Injectables for Submission
PRODUCT A VALIDATION – RISK ASSESSMENT
Failure Mode Effect Analysis (Process)
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5. Developed Work
Production of Injectables for Submission
PRODUCT A VALIDATION – MANUFACTURING PROCESS
Sparge of Addition of
Addition of
WFI with Mixture excipient 1
initial WFI
nitrogen and mixture
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5. Developed Work
Production of Injectables for Submission
PRODUCT A VALIDATION – RESULTS
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5. Developed Work
Production of Injectables for Submission
PRODUCT A VALIDATION – PROCESS OPTIMIZATION
Oxygen Monitored by
headspace PAT tool
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5. Developed Work
Production of Injectables for Submission
PRODUCT B VALIDATION – DESCRIPTION
Injectable used for heart surgery
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5. Developed Work
Production of Injectables for Submission
PRODUCT B VALIDATION – RISK ASSESSMENT
(For Technology Transfer)
Mixing speed 8-12 minutes (excipient) 178-182 minutes Challenging on each step Low. New mixing speeds/times
and time (API). Mixing speed: 550-600 rpm evaluated
Filling Platinum cured silicone tubing Teflon tubing Low. Teflon has lower extractables
Raw-materials API from Reliable. Bedford excipient suppliers Hikma excipient suppliers Low. Compounding evaluated
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5. Developed Work
Production of Injectables for Submission
PRODUCT B VALIDATION – MANUFACTURING PROCESS
Addition of WFI.
Addition of excipient Addition of API.
Adjustment to
1. Mixture Mixture
temperature
Discontinue of
Filling of solution
Adjustment of pH. mixing, sealing of
into vials, stoppering
Mixture vessel and transfer to
and cappsulation
filtration area
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5. Developed Work
Production of Injectables for Submission
PRODUCT B VALIDATION – RESULTS
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5. Developed Work
Production of Injectables for Submission
PRODUCT B VALIDATION – PROCESS OPTIMIZATION
Solution: NIR probe in the compounding tank can control dissolution and assure
a consistent quality product output.
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5. Developed Work
Production of Injectables for Submission
PRODUCT B VALIDATION – SCALE UP
Batch size 50L (8928 units) 200L (7604 units) Maximum size 383 L 1821 L
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6. Conclusions & Future Work
CONCLUSIONS
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6. Conclusions & Future Work
FUTURE WORK
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Development of Injectable Drugs
Technology Transfer and Process Validation
THESIS TO OBTAIN THE MASTER OF SCIENCE DEGREE IN PHARMACEUTICAL ENGINEERING
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