Analytical Scientists in Pharmaceutical Product Development

This book explains task management concepts and outlines practical knowledge to help pharmaceutical analytical scientists become productive and enhance their career.

• Presents broad topics such as product development process, regulatory requirement, task and project management, innovation mindset, molecular recognition, separation science, degradation chemistry, and statistics.

• Provokes thinking through figures, tables, and case studies to help understand how the various functions integrate and how analytical development can work efficiently and effectively by applying science and creativity in their work.

• Discusses how to efficiently develop a fit-for-purpose HPLC method without screening dozens of columns, gradients, or mobile phase combinations each time, since the extra effort may not provide enough of a benefit to justify the cost and time in a fast-paced product development environment.

Auteur

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.

Résumé
This book explains task management concepts and outlines practical knowledge to help pharmaceutical analytical scientists become productive and enhance their career. •Presents broad topics such as product development process, regulatory requirement, task and project management, innovation mindset, molecular recognition, separation science, degradation chemistry, and statistics. •Provokes thinking through figures, tables, and case studies to help understand how the various functions integrate and how analytical development can work efficiently and effectively by applying science and creativity in their work. •Discusses how to efficiently develop a fit-for-purpose HPLC method without screening dozens of columns, gradients, or mobile phase combinations each time, since the extra effort may not provide enough of a benefit to justify the cost and time in a fast-paced product development environment. This book explains task management concepts and outlines practical knowledge to help pharmaceutical analytical scientists become productive and enhance their career.

•Presents broad topics such as product development process, regulatory requirement, task and project management, innovation mindset, molecular recognition, separation science, degradation chemistry, and statistics.

•Provokes thinking through figures, tables, and case studies to help understand how the various functions integrate and how analytical development can work efficiently and effectively by applying science and creativity in their work.

•Discusses how to efficiently develop a fit-for-purpose HPLC method without screening dozens of columns, gradients, or mobile phase combinations each time, since the extra effort may not provide enough of a benefit to justify the cost and time in a fast-paced product development environment.

Contenu
Preface ix

1 Pharmaceutical Development at a Glance 1

1.1 Prescription Medicinal Product Development 1

1.1.1 Active Pharmaceutical Ingredient (API) Development 2

1.1.2 Preclinical Research 3

1.1.3 Clinical Research Phase 1, Safety and Dosage 4

1.1.4 Clinical Research Phase 2, Efficacy and Side Effects 4

1.1.5 Clinical Research Phase 3, Efficacy and Monitoring of Adverse Reactions 4

1.1.6 Clinical Research Phase 4, Post-Market Safety Monitoring 5

1.1.7 FDA Approval of a Prescription Medicine 6

1.2 Over-the-Counter (OTC) Medicinal Product Development 6

1.2.1 FDA Monograph System 7

1.2.2 New Drug Application Process for an OTC Medicinal Product 8

1.2.3 Clinical Trials in OTC Product Development 9

1.2.4 Prescription to OTC Switch 9

References 9

2 Analytics in Fast-Paced Product Development 11

2.1 Overall Development Process for New Products 13

2.2 Regulatory

Strategy and Analytical Development 20

2.2.1 NDA and ANDA Filing 22

2.2.2 Module 3 (CMC) of Common Technical Document 23

2.2.3 Supplements and Other Changes to an Approved NDA or ANDA 26

2.2.3.1 Major Changes Prior Approval Supplement 28

2.2.3.2 Moderate Changes CBE-30 29

2.2.3.3 Moderate Changes CBE 29

2.2.3.4 Minor Changes Annual Report 30

2.2.4 Analytical Development with FDA Guidelines in Mind 30

2.3 ICH Guidelines and Analytical Development 32

2.4 Pharmacopoeia Monographs and Analytical Development 37

2.5 Formulation Development and Analytical Development 38

2.5.1 Method Development Based on an Ideal, Comprehensive Quality by Design 40

2.5.2 Fit-for-Purpose, Teamwork, Knowledge Sharing, and Platform Approach 48

2.6 Methods for Scale-Up and Manufacturing QC Laboratories 55

2.7 Process Analytical Technology 59

2.8 Quality Assurance, Compliance, and Analytical Development 62

References 64

3 Effective, Efficient, and Innovative Analytical Development 67

3.1 Task Management by Fishbone Diagrams and Time-Bars 68

3.2 Project Management Waterfall Versus Agile 82

3.3 Resource and Cost Estimations 88

3.4 Desired Skill Sets 92

3.5 Analytical Scientists and Innovation 94

3.5.1 Think Outside the Box 94

3.5.2 Think Inside the Box 95

3.5.3 Be Analytically Creative 97

References 99

4 Analytical Chemistry and Separation Science at Molecular Level 101

4.1 Ions and Ionic Strength 104

4.2 Protonation and Deprotonation 105

4.3 Hydrolysis of Salts 107

4.4 ChargeDipole and DipoleDipole Interaction 109

4.5 Hydrogen Bonding 110

4.6 Electron DonorAcceptor Interaction 113

4.7 Hydration and Solvation Energy 114

4.8 Hydrophobic Interactions 116

4.9 Events Happening on the Column Surface 118

4.10 Example Thought Processes of Chromatographic Method Development 126

4.10.1 General Considerations 126

4.10.2 Case Study Method Development for Assay of Benzalkonium Chloride 129

4.10.2.1 Method Development 131

4.10.3 Case Study Method Development for Analysis of Stereoisomers 133

4.10.3.1 Considerations of Column Stationary Phases 135

4.10.3.2 Considerations of Mobile Phase Compositions 137

4.10.3.3 Degradation Analysis Method Development 141

References 147

5 Degradation Chemistry and Product Development 151

5.1 Hydrolysis 152

5.2 Oxidation 155

5.3 Reactions of Common Functional Groups 160

5.3.1 Carboxylic Acid 160

5.3.2 Hydroxyl Group 162

5.3.3 CarbonCarbon Double Bond 163

5.3.4 Amine Reactions 164

5.4 Summary of API Degradations 168 5.5 Stability Study and Forced Deg...