Quality Systems and Controls for Pharmaceuticals

List of figures xv

List of tables xix

Glossary of terms and acronyms xxi

Glossary of mathematical and statistical symbols xxiii

SECTION A Most Suitable Environment 1

1. Introduction 3
1.1 The process of finding new lead medicines 4
1.2 A drug discovery framework 6

2. Technology transfer and the climate of change 11
2.1 Innovation and research 11
2.2 Method transfer 14

3. Quality systems structure and a maximum quality environment 15
3.1 The quality gurus and models for assurance 18
3.2 A cycle of continual improvement 22
3.3 Management structure and a functioning department 22

SECTION B Setting Process Bounderies 29

4. Validation 31
4.1 Process and manufacturing validation activities 35
4.2 Valid analytical methodologies (VAMs) 43

5. Good manufacturing practices 57
5.1 Manufacture of standard products 60
5.2 Manufacture of materials requiring specialised production facilities 75
5.3 Quality assurance aspects of medical gases, devices and miscellaneous product manufacture 88

6. Process control via numerical means 97
6.1 Charting and quality inspection 99
6.2 Sampling plans 104
6.3 Measures of process compliance and variation 108

7. Product verification and the role of qualified personnel 111
7.1 Batch documentation 113
7.2 Standard operating procedures 114
7.3 Guides, overviews and validation plans 115
7.4 The duties of the qualified person 116

8. In-process and on-process QC testing and control 119
8.1 Process analytical technologies 120
8.2 Analytical validation and clinical test validation (CTV) 121
8.3 LIMS and automation 126

SECTION C Starting from Scratch 131

9. Applications of QA to new medicinal products and new chemical entities formulation 133
9.1 Start-up and initialisation 134
9.2 Raw materials control 134
9.3 The validation life cycle 134
9.4 Top-down or bottom-up validations 135

10. New products manufacturing 137
10.1 From inception to market place 139
10.2 New product development: product design and specification 146

11. Questions and problems 151
11.1 Specimen examples and exam questions 151
11.2 Model answers to examples 162

References 169

Index 177