Method Validation in Pharmaceutical Analysis

Foreword ANALYTICAL VALIDATION WITHIN THE PHARMACEUTICAL LIFECYCLE Development of Process and Analytical Validation Concepts Alignment between Process and Analytics: Three-Stage Approach Predefined Objectives: Analytical Target Profile Analytical Life Cycle ANALYTICAL INSTRUMENT QUALIFICATION Analytical Instrument and System Qualification Efficient and Economic HPLC Performance Qualification ESTABLISHMENT OF MEASUREMENT REQUIREMENTS - ANALYTICAL TARGET PROFILE AND DECISION RULES Introduction Defining the Fitness for Intended Use Decision Rules Overview of Process to Develop Requirements for Procedure Performance Decision Rules and Compliance Calculating Target Measurement Uncertainty Types of Decision Rules Target Measurement Uncertainty in the Analytical Target Profile Bias and Uncertainty in a Procedure ATP and Key Performance Indicators Measurement Uncertainty Example Conclusion ESTABLISHMENT OF MEASUREMENT REQUIREMENTS - PERFORMANCE-BASED SPECIFICATION Introduction Intended Purpose Identification Assay Impurities Limit Tests Quantitative Tests Summary METHOD PERFORMANCE CHARACTERISTICS Introduction Precision Accuracy and Range Specificity Linearity Detection and Quantitation Limit Glossary METHOD DESIGN AND UNDERSTANDING Introduction Analytical Quality by Design and Robustness Investigations Case Study: Robustness Investigations System Suitability Tests METHOD PERFORMANCE QUALIFICATION Introduction Case Study: Qualification of an HPLCMethod for Identity, Assay, and Degradation Products Design and Qualification of a Delivered Dose Uniformity Procedure for a Pressurized Metered Dose Inhaler Implementation of Compendial/Pharmacopeia Test Procedures Transfer of Analytical Procedures CONTINUED METHOD PERFORMANCE VERIFICATION Introduction Routine Monitoring Investigating and Addressing Aberrant Data Continual Improvement Index

Joachim Ermer is Head of Quality Control Services Chemistry at Sanofi in Frankfurt, Germany, and Global Reference Standards Coordinator of Sanofi. He studied biochemistry at University of Halle, Germany, and obtained a PhD in enzyme kinetics in 1988. He has more than 20 years of experience in pharmaceutical analytics including development projects, global responsibilities as Director of Analytical Processes and Technology, and Head of Quality Control. He is member of the USP Expert Panel on Validation and Verification, of the EFPIA Quality by Design Working Group, and of the Focus Group Analytics and Quality Assurance of the International Association of Pharmaceutical Technology (APV). From 2000 till 2008, he was Deputy Head of the Working Group Quality Control / Pharmaceutical Analytics of the German Pharmaceutical Society (DPhG). His special interest has been focused early on analytical validation and related topics, such as performance evaluation, statistics, and transfer of analytical procedures.. Phil Nethercote is the Analytical Head and API Analytical Lead for the Global Manufacturing and Supply division of GSK. He has a degree in chemistry from Herriot Watt University in Edinburgh and obtained a PhD in HPLC retention mechanisms from the University of Stirling in 1987. He is a Chartered Chemist and a member of the Royal Society of Chemistry. He has over 25 years of experience in the pharmaceutical industry the majority of which has been with Glaxo, Glaxo Wellcome and GSK where he has led analytical development and new product introduction teams in the UK and in Singapore. In his current role he provides leadership for analytical systems, processes and standards across GSKs global network of manufacturing sites. He is member of the USP Expert Panel on Validation and Verification, of the EFPIA Analytical Quality by Design Working Group and led the revision of the analytical section of the second edition of the ISPE technology transfer guide He has a passion for