PROCESS VALIDATION (PV)
Interactive Overview Dashboard
Process Validation
Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.
Purpose
- Demonstrate process consistency
- Minimize product variability
- Ensure regulatory compliance
- Reduce quality risks
When Done
Process validation is performed following successful development and process characterization, but prior to commercial distribution. It bridges the gap between R&D and full-scale manufacturing.
Stage 2: Process QualificationPV Protocol
- Objective and Scope: Define validation goals
- Batch Size and Number: Typically 3 consecutive batches
- Critical Parameters: CPPs and CQAs identification
- Responsibilities: Define roles and approvals
- Acceptance Criteria: Pre-defined limits
PV Report
- Executive summary
- Data analysis and trending
- Deviation assessment
- Conclusion on process capability
- Recommendations for improvements
Compliance
- 21 CFR Part 211.100 & 211.110
- EU GMP Annex 15
- ICH Q7, Q8, Q9, Q10, Q11
- GAMP 5 Guidelines
Continuous Improvement Framework
📈 Trend Analysis
Ongoing monitoring of critical process parameters and quality attributes to identify patterns and potential issues before they impact product quality.
🔄 CAPA System
Corrective and Preventive Actions to address deviations, enhance process understanding, and drive continuous improvement initiatives.
🔍 Stage 3 Validation
Continued Process Verification through ongoing monitoring, periodic reviews, and statistical process control throughout product lifecycle.
🎲 Risk-Based Validation Approach
ICH Q9 Risk Management
- Risk Identification: FMEA/FMECA, Hazard Analysis
- Risk Assessment: Severity × Probability × Detectability
- Risk Control: Mitigation strategies for CPPs
- Risk Review: Periodic reassessment and trending
GAMP 5 Category Approach
- Category 3: Non-configured products (standard validation)
- Category 4: Configured products (configuration testing)
- Category 5: Custom applications (full CSV/CSA)
Scalable Approach: Validation effort proportional to system complexity, business risk, and patient safety impact per GAMP 5 RBA principles.
Critical Thinking Methodology
- CPPs: Critical Process Parameters affecting CQAs
- CQAs: Critical Quality Attributes for product safety/efficacy
- Design Space: Proven acceptable ranges (ICH Q8)
- Control Strategy: How CPPs are monitored and controlled
🔒 ALCOA+ Data Integrity Principles
Attributable
Data traceable to individual who generated it (21 CFR Part 11 e-signatures, audit trails)
Legible
Data must be readable and permanent throughout retention period
Contemporaneous
Data recorded at time of activity, not retrospectively entered
Original
First capture of data or certified true copy with metadata
Accurate
Data free from errors, complete, and reflects true observation
Complete, Consistent, Enduring, Available
Full data lifecycle integrity from creation through retention and retrieval
🔄 Process Validation Lifecycle (FDA Guidance 2011)
Process Design
Quality by Design (QbD) approach defining commercial manufacturing process based on development and scale-up knowledge
- Design of Experiments (DOE)
- Risk assessments (FMEA)
- Process characterization
- URS/FRS development
Process Qualification
Evaluation confirming process capable of reproducible commercial manufacturing (PV focus area)
- Design Qualification (DQ)
- Installation Qualification (IQ)
- Operational Qualification (OQ)
- Performance Qualification (PQ)
Continued Process Verification
Ongoing assurance that process remains in control during routine production
- Real-time release testing (RTRT)
- Statistical Process Control (SPC)
- Annual Product Review (APR)
- Periodic revalidation