Analytical Scientists in Pharmaceutical Product Development: Task Management and Practical Knowledge

ISBN-13: 9781119547822 / Angielski / Twarda / 2020 / 272 str.

Kangping Xiao

Spis treści

Preface ix1 Pharmaceutical Development at a Glance 11.1 Prescription Medicinal Product Development 11.1.1 Active Pharmaceutical Ingredient (API) Development 21.1.2 Preclinical Research 31.1.3 Clinical Research - Phase 1, Safety and Dosage 41.1.4 Clinical Research - Phase 2, Efficacy and Side Effects 41.1.5 Clinical Research - Phase 3, Efficacy and Monitoring of Adverse Reactions 41.1.6 Clinical Research - Phase 4, Post-Market Safety Monitoring 51.1.7 FDA Approval of a Prescription Medicine 61.2 Over-the-Counter (OTC) Medicinal Product Development 61.2.1 FDA Monograph System 71.2.2 New Drug Application Process for an OTC Medicinal Product 81.2.3 Clinical Trials in OTC Product Development 91.2.4 Prescription to OTC Switch 9References 92 Analytics in Fast-Paced Product Development 112.1 Overall Development Process for New Products 132.2 RegulatoryStrategy and Analytical Development 202.2.1 NDA and ANDA Filing 222.2.2 Module 3 (CMC) of Common Technical Document 232.2.3 Supplements and Other Changes to an Approved NDA or ANDA 262.2.3.1 Major Changes - Prior Approval Supplement 282.2.3.2 Moderate Changes - CBE-30 292.2.3.3 Moderate Changes - CBE 292.2.3.4 Minor Changes - Annual Report 302.2.4 Analytical Development with FDA Guidelines in Mind 302.3 ICH Guidelines and Analytical Development 322.4 Pharmacopoeia Monographs and Analytical Development 372.5 Formulation Development and Analytical Development 382.5.1 Method Development Based on an Ideal, Comprehensive Quality by Design 402.5.2 Fit-for-Purpose, Teamwork, Knowledge Sharing, and Platform Approach 482.6 Methods for Scale-Up and Manufacturing QC Laboratories 552.7 Process Analytical Technology 592.8 Quality Assurance, Compliance, and Analytical Development 62References 643 Effective, Efficient, and Innovative Analytical Development 673.1 Task Management by Fishbone Diagrams and Time-Bars 683.2 Project Management - Waterfall Versus Agile 823.3 Resource and Cost Estimations 883.4 Desired Skill Sets 923.5 Analytical Scientists and Innovation 943.5.1 Think Outside the Box 943.5.2 Think Inside the Box 953.5.3 Be Analytically Creative 97References 994 Analytical Chemistry and Separation Science at Molecular Level 1014.1 Ions and Ionic Strength 1044.2 Protonation and Deprotonation 1054.3 Hydrolysis of Salts 1074.4 Charge-Dipole and Dipole-Dipole Interaction 1094.5 Hydrogen Bonding 1104.6 Electron Donor-Acceptor Interaction 1134.7 Hydration and Solvation Energy 1144.8 Hydrophobic Interactions 1164.9 Events Happening on the Column Surface 1184.10 Example Thought Processes of Chromatographic Method Development 1264.10.1 General Considerations 1264.10.2 Case Study - Method Development for Assay of Benzalkonium Chloride 1294.10.2.1 Method Development 1314.10.3 Case Study - Method Development for Analysis of Stereoisomers 1334.10.3.1 Considerations of Column Stationary Phases 1354.10.3.2 Considerations of Mobile Phase Compositions 1374.10.3.3 Degradation Analysis Method Development 141References 1475 Degradation Chemistry and Product Development 1515.1 Hydrolysis 1525.2 Oxidation 1555.3 Reactions of Common Functional Groups 1605.3.1 Carboxylic Acid 1605.3.2 Hydroxyl Group 1625.3.3 Carbon-Carbon Double Bond 1635.3.4 Amine Reactions 1645.4 Summary of API Degradations 1685.5 Stability Study and Forced Degradation 1695.5.1 Guidelines on Long-Term Stability Study 1695.5.2 Forced Degradation Study Considerations 1715.6 Excipient Compatibility 1745.6.1 General Remarks 1745.6.2 Direct Reactions Between APIs and Excipients 1755.6.3 Impurities in Excipients 1765.6.4 Solid-State Stability - Role of Water 1775.6.5 Experimental Considerations - Formulation Relevancy 1805.7 Accelerated Stability Evaluation of Finished Products 183References 1866 Practical Statistics for Analytical Development 1936.1 Basic Statistical Terms 1956.1.1 Sample Versus Population 1956.1.2 Mean, Variance, Standard Deviation, and Relative Standard Deviation 1966.1.3 Normal Distribution 1996.1.4 t-Statistics, F-Test, and ANOVA 2016.1.5 Hypothesis Setting 2056.1.6 Level of Significance and p-Value 2116.1.7 Confidence Interval, Prediction Interval, and Tolerance Interval 2146.2 Application of Statistics - Analytical Method Equivalency 2196.3 Application of Statistics - Stability Data Trending 224References 2267 Thoughts on Conventional Chromatography Practices 2297.1 Linear Regression 2297.2 Response Factor, Linearity Slope, and y-Intercept 2327.3 Relative Response Factor, Linearity Slope, and y-Intercept 2357.4 Linearity and Method Accuracy 2387.5 Injection Precision in System Suitability 2407.6 Sample Preparation 2427.7 Method Validation and Transfer: Mathematical Exercises or Analytical Sciences 2457.8 Miscellaneous Considerations 249References 251Index 253

O autorze

Kangping Xiao - Head of Analytical Development, Bayer Consumer Health R&D in NJ. His team plays critical roles in new product development such as the launch of Aleve PM, Claritin Cool Mint Chewables, and various Aspirin containing products globally. Bachelor of Science Wuhan University, Ph.D. University of Tokyo, Postdoctoral Michigan State University and University of Michigan.