Method Validation in Pharmaceutical Analysis

Chapter 1: Analytical Validation Within the Pharmaceutical Lifecycle

• • 1.1 Development of Process and Analytical Validation Concepts
• • 1.2 Alignments Between Process and Analytics: Three-Stage Approach
• • 1.3 Predefined Objectives: ATP
• • 1.4 Analytical Lifecycle
• • References

Chapter 2: Data Governance, Data Integrity, and Data Quality

• • 2.1 Terminology Used in This Chapter
• • 2.2 Data Governance and Data Integrity Model
• • 2.3 Interaction Between Levels 1 and 2
• • 2.4 Overview of Data Integrity
• • 2.5 ALCOA Criteria for Data Integrity
• • 2.6 Understanding Level 3: Right Analysis for the Right Reportable Result
• • 2.7 Second-Person Review
• • 2.8 Summary
• • References

Chapter 3: Analytical Instrument Qualification and System Validation Lifecycle

• • 3.1 Data Integrity and Data Quality in a GMP Environment
• • 3.2 AIQSV Approach as an Essential Part of the Analytical Procedure Lifecycle
• • 3.3 USP General Chapter <1058>
• • 3.4 Enhancement of <1058> and Harmonization of a Risk-Based Approach to Instruments and Systems with GAMP
• • 3.5 Risk-Based Approaches to Analytical Instrument and System Qualification [3]
• • References

Chapter 4: Continued HPLC Performance Qualification

• • 4.1 Introduction
• • 4.2 Development of the Revised OQ/PQ Parameters List
• • 4.3 Transfer of Modular Parameters into the Holistic Approach
• • 4.4 OQ/PQ Data in Comparison with SST Data
• • 4.5 Performance Monitoring: Trending Plots/Control Charts
• • 4.6 General Procedure for cPQ
• • 4.7 Example
• • 4.8 Concluding Remarks
• • Acknowledgment
• • References

Chapter 5: Analytical Target Profile

• • 5.1 Introduction
• • 5.2 Components of an ATP
• • 5.3 The Probability Statements
• • 5.4 Metrics for Assessment
• • 5.5 Summary
• • Acknowledgments
• • References

Chapter 6: Decision Rules and Fitness for Intended Purpose

• • 6.1 Introduction
• • 6.2 Defining the Fitness for Intended Purpose
• • 6.3 Decision Rules
• • 6.4 Overview of Process to Develop Requirements for Procedure Performance
• • 6.5 Decision Rules and Compliance
• • 6.6 Calculating Target Measurement Uncertainty
• • 6.7 Types of Decision Rules
• • 6.8 Target Measurement Uncertainty in the ATP
• • 6.9 Bias and Uncertainty in a Procedure
• • 6.10 ATP and Key Performance Indicators
• • 6.11 Measurement Uncertainty
• • 6.12 Example
• • 6.13 Conclusion
• • References

Chapter 7: Performance Characteristics of Analytical Procedures

• • 7.1 Precision
• • 7.2 Accuracy
• • 7.3 Specificity/Selectivity
• • 7.4 Response (Calibration Model)
• • 7.5 Detection and Quantitation Limits
• • Acknowledgments
• • References

Chapter 8: ICHQ14 Analytical Procedure Development

• • 8.1 Introduction
• • 8.2 The ATP
• • 8.3 Connection Between Product and Analytical Procedure Understanding
• • 8.4 Prior and Platform Knowledge
• • 8.5 Robustness and Method Operable Design Region (MODR)
• • 8.6 Link and Impact with Analytical Procedure Validation
• • 8.7 Analytical Procedure Control Strategy and Ongoing Procedure Performance Verification
• • 8.8 Lifecycle Strategy Including Enhanced Approaches in Submission
• • 8.9 Summary
• • References

Chapter 9: Method Selection, Development, and Optimization

• • 9.1 Introduction
• • 9.2 Method Selection
• • 9.3 Method Development
• • 9.4 Method Optimization
• • Acknowledgments
• • References

Chapter 10: Multivariate Analytical Procedures

• • 10.1 Introduction
• • 10.2 Sampling and Data Quality
• • 10.3 Development of Multivariate Models
• • 10.4 Model Optimization and Validation
• • 10.5 Model Maintenance and Lifecycle Management
• • 10.6 Summary
• • Acknowledgments
• • References

Chapter 11: Case Study: Robustness Investigations

• • 11.1 Introduction
• • 11.2 General Considerations in the Context of Robustness Testing
• • 11.3 Examples of Computer-Assisted Robustness Studies
• • Acknowledgment
• • References

Chapter 12: Risk Assessment and Analytical Procedure Control Strategy

• • 12.1 Background
• • 12.2 Risk Management Process
• • 12.3 ICH Q9
• • 12.4 Using Risk Management to Develop a Control Strategy
• • 12.5 Analytical Procedure Control Strategy
• • References

Chapter 13: ICH Q2(R2): Validation of Analytical Procedures

• • 13.1 How to Read This Chapter
• • 13.2 Introduction
• • 13.3 General Considerations for Analytical Procedure Validation
• • 13.4 Validation Tests, Methodology, and Evaluation
• • 13.5 Annex 2: Illustrative Examples for Analytical Techniques
• • 13.6 Conclusion
• • References

Chapter 14: Case Study: Validation of a High-performance Liquid Chromatography (HPLC) Method for Identity, Assay, and Degradation of Products

• • 14.1 Introduction
• • 14.2 Experimental
• • 14.3 Validation Summary
• • 14.4 Validation Methodology
• • 14.5 Conclusion
• • References

Chapter 15: Case Study: Design and Qualification of a Delivered Dose Uniformity Procedure for a Pressurized Metered Dose Inhaler with a Focus on Sample Preparation

• • 15.1 Introduction
• • 15.2 Designing a DDU Procedure that will Meet an ATP
• • 15.3 Performance Characteristics of the DDU Procedure
• • 15.4 Qualification of the DDU Procedure
• • 15.5 Summary of the Analytical Procedure Control Strategy for a DDU Procedure
• • Acknowledgments
• • References

Chapter 16: Case Study: Validation of a Bioassay Method

• • 16.1 Introduction
• • 16.2 Material Considerations
• • 16.3 Study Design
• • 16.4 Specificity/Selectivity
• • 16.5 Accuracy
• • 16.6 Precision
• • 16.7 Range
• • 16.8 Robustness
• • 16.9 Conclusion
• • Acknowledgments
• • References

Chapter 17: Implementation of Compendial/Pharmacopeia Test Procedures

• • 17.1 Background of Pharmacopeia Procedures
• • 17.2 How Pharmacopeia Methods Are Generated and Published
• • 17.3 Challenges with Compendial Procedures and the Need to Verify
• • 17.4 Using Pharmacopeia Procedures in a Laboratory for the First Time
• • 17.5 Verification of Pharmacopeia Procedures
• • 17.6 Integration of the Verification Process and the Lifecycle Approach
• • 17.7 Implementation of a Pharmacopeia Procedure Using the Lifecycle Approach
• • 17.8 Performance Qualification
• • 17.9 Conclusion
• • References

Chapter 18: Transfer of Analytical Procedures

• • 18.1 Transfer Process and Strategy
• • 18.2 Comparative Testing
• • References

Chapter 19: Lifecycle Approach to Transfer of Analytical Procedures

• • 19.1 Facilitation of Transfer by Risk Assessment
• • 19.2 Facilitation of Transfer by the APCS
• • 19.3 “Lean” Transfer Strategy
• • 19.4 Conclusion
• • References

Chapter 20: Continuous Improvements, Adjustments, and Changes

• • 20.1 Drivers for Change
• • 20.2 Control of Change in the Pharmaceutical Industry
• • 20.3 Implementing a Change
• • References

Chapter 21: Monitoring of Analytical Performance

• • 21.1 Sources of Performance Data and Information
• • 21.2 Systematic Monitoring Program
• • 21.3 Analytical Performance Evaluation Tools
• • 21.4 Assessment of Analytical Performance
• • 21.5 Conclusion
• • References