Pharmaceutical Quality by Design

A practical guide to Quality by Design for pharmaceutical product development

Pharmaceutical Quality by Design: A Practical Approach outlines a new and proven approach to pharmaceutical product development which is now being rolled out across the pharmaceutical industry internationally. Written by experts in the field, the text explores the QbD approach to product development. This innovative approach is based on the application of product and process understanding underpinned by a systematic methodology which can enable pharmaceutical companies to ensure that quality is built into the product.

Familiarity with Quality by Design is essential for scientists working in the pharmaceutical industry. The authors take a practical approach and put the focus on the industrial aspects of the new QbD approach to pharmaceutical product development and manufacturing. The text covers quality risk management tools and analysis, applications of QbD to analytical methods, regulatory aspects, quality systems and knowledge management. In addition, the book explores the development and manufacture of drug substance and product, design of experiments, the role of excipients, multivariate analysis, and include several examples of applications of QbD in actual practice. This important resource:

• Covers the essential information about Quality by Design (QbD) that is at the heart of modern pharmaceutical development
• Puts the focus on the industrial aspects of the new QbD approach
• Includes several illustrative examples of applications of QbD in practice
• Offers advanced specialist topics that can be systematically applied to industry

Pharmaceutical Quality by Design offers a guide to the principles and application of Quality by Design (QbD), the holistic approach to manufacturing that offers a complete understanding of the manufacturing processes involved, in order to yield consistent and high quality products.

Auteur

Editors Walkiria S. Schlindwein is Associate Professor of Pharmaceutics at the School of Pharmacy, De Montfort University. Walkiria is the programme leader of two Postgraduate courses in Pharmaceutical Quality by Design. Mark Gibson is Director of AM PharmaServices Ltd. He is a practicing Pharmaceutical Consultant and was formerly with AstraZeneca.

Résumé
A practical guide to Quality by Design for pharmaceutical product development Pharmaceutical Quality by Design: A Practical Approach outlines a new and proven approach to pharmaceutical product development which is now being rolled out across the pharmaceutical industry internationally. Written by experts in the field, the text explores the QbD approach to product development. This innovative approach is based on the application of product and process understanding underpinned by a systematic methodology which can enable pharmaceutical companies to ensure that quality is built into the product. Familiarity with Quality by Design is essential for scientists working in the pharmaceutical industry. The authors take a practical approach and put the focus on the industrial aspects of the new QbD approach to pharmaceutical product development and manufacturing. The text covers quality risk management tools and analysis, applications of QbD to analytical methods, regulatory aspects, quality systems and knowledge management. In addition, the book explores the development and manufacture of drug substance and product, design of experiments, the role of excipients, multivariate analysis, and include several examples of applications of QbD in actual practice. This important resource: Covers the essential information about Quality by Design (QbD) that is at the heart of modern pharmaceutical development Puts the focus on the industrial aspects of the new QbD approach Includes several illustrative examples of applications of QbD in practice Offers advanced specialist topics that can be systematically applied to industry Pharmaceutical Quality by Design offers a guide to the principles and application of Quality by Design (QbD), the holistic approach to manufacturing that offers a complete understanding of the manufacturing processes involved, in order to yield consistent and high quality products.

Contenu

List of Figures xiii

List of Tables xix

List of Contributers xxi

Series Preface xxiii

Preface xxv

1 Introduction to Quality by Design (QbD) 1
*Bruce Davis and Walkiria S. Schlindwein*

1.1 Introduction 1

1.2 Background 2

1.3 Science?] and Risk?]Based Approaches 4

1.4 ICH Q8-Q12 5

1.5 QbD Terminology 6

1.6 QbD Framework 7

1.7 QbD Application and Benefits 7

1.8 Regulatory Aspects 8

1.9 Summary 9

1.10 References 9

2 Quality Risk Management (QRM) 11
*Noel Baker*

2.1 Introduction 11

2.2 Overview of ICH Q9 13

2.2.1 Start QRM Process 15

2.2.2 Risk Assessment 15

2.2.3 Risk Control 16

2.2.4 Risk Review 16

2.3 Risk Management Tools 17

2.4 Practical Examples of Use for QbD 22

2.4.1 Case Study 26

2.4.2 Pre?]work 26

2.4.3 Scoring Meeting 32

2.4.4 FMECA Tool 32

2.4.5 Risk Score 32

2.4.6 Detectability Score 34

2.4.7 Communication 35

2.5 Concluding Remarks 36

2.6 References 44

3 Quality Systems and Knowledge Management 47
*Siegfried Schmitt*

3.1 Introduction to Pharmaceutical Quality System 47

3.1.1 Knowledge Management - What Is It and Why Do We Need It? 47

3.2 The Regulatory Framework 48

3.2.1 Knowledge Management in the Context of Quality by Design (QbD) 48

3.2.2 Roles and Responsibilities for Quality System 49

3.2.3 Roles and Responsibilities for Knowledge Management 50

3.2.4 Implicit and Explicit Knowledge 50

3.3 The Documentation Challenge 51

3.4 From Data to Knowledge: An Example 56

3.5 Data Integrity 58

3.6 Quality Systems and Knowledge Management: Common Factors for Success 58

3.7 Summary 59

3.8 References 60

4 Quality by Design (QbD) and the Development and Manufacture of Drug Substance 61
*Gerry Steele*

4.1 Introduction 61

4.2 ICH Q11 and Drug Substance Quality 62

4.2.1 Enhanced Approach 63

4.2.2 Impurities 63

4.2.3 Physical Properties of Drug Substance 64

4.3 Linear and Convergent Synthetic Chemistry Routes 65

4.4 Registered Starting Materials (RSMs) 67

4.5 Definition of an Appropriate Manufacturing Process 68

4.5.1 Crystallization, Isolation and Drying of APIs 68

4.5.2 Types of Crystallization 69

4.5.3 Design of Robust Cooling Crystallization 70

4.6 In?]Line Process Analytical Technology and Crystallization Processes 78

4.6.1 Other Unit Operations 80

4.7 Applying the QbD Process 82

4.7.1 Quality Risk Assessment (QRA) 83

4.8 Design of Experiments (DoE) 87

4.9 Critical Process Parameters (CPPs) 88

4.10 Design Space 88

4.11 Control Strategy 89

4.12 References 91

5 The Role of Excipients in Quality by Design (QbD) 97
*Brian Carlin*

5.1 Introduction 97

5.2 Quality of Design (QbD) 98

5.3 Design of Experiments (DoE) 100

5.4 Excipient Complexity 102

5.5 Composition 105

5.6 Drivers of Functionality or Performance 105

5.7 Limited Utility of Pharmacopoeial Attributes 106

5.8 Other Unspecified Attributes 107

5.9 Variability 107

5.10 Criticalities or Latent Conditions in the Finished Product 108

5.11 Direct or Indirect Impact of Excipient Variability 110

5.12 Control Strategy 111

5.13 Communication with Suppliers 112

5.14 Build in Compensatory Flexibility 113

5.15 Risk Assessment 113

5.16 Contingencies 114

5.17 References 114

6 Development and Manufacture of Drug Product 117
*Mark Gibson, Alan Carmody, and Roger Weaver*

6.1 Introduction 117

6.2 Applying QbD to Pharmaceutical Drug Product Development 119

6.3 Product Design Intent and the Target Product Profile (TPP) 120

6.4 The Quality Target Product Profile (QTPP) 126

6.5 Identi…