Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals

Tim Sandle is Head of Microbiology at the Bio Products Laboratory, Elstree, UK and a visiting tutor with the School of Pharmacy and Pharmaceutical Sciences, Manchester University, UK.

Dedication

List of figures and tables

Preface

About the author

Introduction

Chapter 1: Sterility, sterilisation and microorganisms

Abstract:

1.1 Introduction

1.2 Sterility

1.3 Sterility Assurance and the Sterility Assurance Level (SAL)

1.4 Sterility testing

1.5 Parametric release

1.6 Sterile products

1.7 Sterilisation

1.8 Factors affecting sterilisation

1.9 Risk assessment

1.10 Conclusion

Chapter 2: Pyrogenicity bacterial endotoxin

Abstract:

2.1 Introduction

2.2 Pyrogenicity

2.3 Endotoxin

2.4 The LAL test

2.5 Alternative assays

2.6 Water: the source of endotoxins in pharmaceutical manufacturing

2.7 Conclusion

Chapter 3: Regulatory requirements and Good Manufacturing Practices (GMP)

Abstract

3.1 Introduction

3.2 A brief history of compliance

3.3 Key terminology

3.4 Current regulatory requirements

3.5 Federal Drug Administration (FDA)

3.6 European Good Manufacturing Practices

3.7 Pharmaceutical Inspection Convention (PIC) and the Pharmaceutical Inspection Co-operation Scheme (PIC Scheme)

3.8 World Health Organisation

3.9 ISO

3.10 ICH

3.11 Pharmacopoeias

3.12 National standards

3.13 Other sources of guidance

3.14 Regulatory inspections

3.15 Conclusion

Chapter 4: Gamma radiation

Abstract:

4.1 Introduction

4.2 Application of gamma radiation

4.3 Sterilisation method

4.4 Process requirements

4.5 Regulatory aspects

4.6 Conclusion

Chapter 5: Electron beam processing

Abstract:

5.1 Introduction

5.2 Application of e-beam radiation

5.3 Sterilisation method

5.4 Microbial destruction

5.5 Process requirements

5.6 Advantages of e-beam radiation

5.7 Disadvantages of e-beam radiation

5.8 Conclusion

Chapter 6: Dry heat sterilisation

Abstract:

6.1 Introduction

6.2 Microbial kill and endotoxin inactivation

6.3 Application of dry heat sterilisation

6.4 Validation of dry heat devices

6.5 Advantages and disadvantages of dry heat sterilisation

6.6 Conclusion

Chapter 7: Steam sterilisation

Abstract:

7.1 Introduction

7.2 Microbial destruction

7.3 Steam sterilisation devices

7.4 Applications of steam sterilisation

7.5 Cycle development

7.6 Validation of steam sterilisation cycles

7.7 In-use evaluation

7.8 Flash sterilisation

7.9 Advantages and disadvantages of steam sterilisation

7.10 Conclusion

Chapter 8: Gaseous sterilisation

Abstract:

8.1 Introduction

8.2 Applications

8.3 Ethylene oxide

8.4 Ozone

8.5 Chlorine dioxide gas

8.6 Summary

Chapter 9: Hydrogen peroxide vapour sterilisation

Abstract:

9.1 Introduction

9.2 Chemical composition

9.3 Antimicrobial effectiveness

9.4 Barrier devices and isolators

9.5 HVP cycles

9.6 Validating VHP cycles

9.7 Cycle failures

9.8 Conclusion

Chapter 10: Sterilisation by filtration

Abstract:

10.1 Introduction

10.2 Sterilising grade filters

10.3 Application of sterilising grade filters

10.4 Filter testing

10.5 Filter failures

10.6 Selection of sterilising grade filters

10.7 Validation of sterilising grade filters

10.8 Conclusion

Chapter 11: Other methods of sterilisation

Abstract:

11.1 Introduction

11.2 Ultraviolet light

11.3 Pulsed light

11.4 Microwaves

11.5 Infrared radiation

11.6 Ultrasonics

11.7 Supercritical gases

11.8 Formaldehyde steam

11.9 X-rays

11.10 Plasma

11.11 Nitrogen dioxide

11.12 Non-sterilising processes

11.13 Conclusion

Chapter 12: Depyrogenation and endotoxin

Abstract:

12.1 Introduction

12.2 Different types of depyrogenation

12.3 Case study 1: Dry heat depyrogenation

12.4 Case study 2: Removal of endotoxin through rinsing

12.5 Conclusion

Chapter 13: Cleanrooms, isolators and cleanroom technology

Abstract:

13.1 Introduction

13.2 Cleanrooms and contamination control

13.3 Cleanroom classification

13.4 Cleanroom operating conditions

13.5 Measuring the physical operation of cleanrooms

13.6 Clean air devices and isolators

13.7 Ongoing monitoring

13.8 Conclusion

Chapter 14: Aseptic processing filling

Abstract:

14.1 Introduction

14.2 Selecting aseptic manufacture in place of terminal sterilisation

14.3 Regulatory aspects

14.4 Aseptic processing risks and sources of contamination

14.5 Contamination control

14.6 Types of aseptic filling

14.7 Single-use sterile disposable items

14.8 Conclusion

Chapter 15: Media simulation trials

Abstract:

15.1 Introduction

15.2 Defining a media simulation trial

15.3 Objectives of a media simulation trial

15.4 The media trial protocol

15.5 Conducting media simulation trials

15.6 Frequency of media simulation trials

15.7 Media fill failures

15.8 Media fill invalidation

15.9 Conclusion

Chapter 16: Cleaning disinfection of sterile processing facilities

Abstract:

16.1 Introduction

16.2 Cleaning

16.3 Disinfection

16.3.3 Factors affecting disinfectant efficacy

16.4 Cleaning and disinfection in practice

16.5 Environmental monitoring

16.6 Validation of disinfectants

16.7 Conclusion

Chapter 17: Biological indicators

Abstract:

17.1 Introduction

17.2 Application of biological indicators

17.3 Characteristics of biological indicators

17.4 Use of biological indicators

17.5 Areas of concern and testing errors

17.6 Conclusion

Chapter 18: The Sterility Test

Abstract:

18.1 Introduction

18.2 Sterility Test methods

18.3 Pharmacopeia Sterility Test

18.4 Test environment

18.5 Sterility Test media

18.6 Sterility Test method validation

18.7 Stasis Test

18.8 GMP requirements

18.9 Can the Sterility Test really confirm product sterility?

18.10 Rapid microbiological methods

18.11 Conclusion

Chapter 19: Investigating sterility test failures

Abstract:

19.1 Introduction

19.2 Failure investigations

19.3 Sterility Test and process area link

19.4 Re-testing

19.5 Concluding Sterility Test failure investigations

19.6 Conclusion

Chapter 20: Auditing sterilisation processes facilities

Abstract:

20.1 Introduction

20.2 The audit process

20.3 Scope of audits

20.4 Key focal points for auditing sterile manufacturing facilities

20.5 Conclusion

Conclusion

Index