Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals - 1st Edition - ISBN: 9781907568381, 9781908818638

Sterility, Sterilisation and Sterility Assurance for Pharmaceuticals

1st Edition

Technology, Validation and Current Regulations

Authors: Tim Sandle
eBook ISBN: 9781908818638
Hardcover ISBN: 9781907568381
Imprint: Woodhead Publishing
Published Date: 31st October 2013
Page Count: 362
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Table of Contents


List of figures and tables


About the author


Chapter 1: Sterility, sterilisation and microorganisms


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


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)


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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




Failure to adequately control any microbial challenge associated within process or product by robust sterilisation will result in a contaminated marketed product, with potential harm to the patient. Sterilisation is therefore of great importance to healthcare and the manufacturers of medical devices and pharmaceuticals. Sterility, sterilisation and sterility assurance for pharmaceuticals examines different means of rendering a product sterile by providing an overview of sterilisation methods including heat, radiation and filtration. The book outlines and discusses sterilisation technology and the biopharmaceutical manufacturing process, including aseptic filling, as well as aspects of the design of containers and packaging, as well as addressing the cleanroom environments in which products are prepared. Consisting of 18 chapters, the book comprehensively covers sterility, sterilisation and microorganisms; pyrogenicity and bacterial endotoxins; regulatory requirements and good manufacturing practices; and gamma radiation. Later chapters discuss e-beam; dry heat sterilisation; steam sterilisation; sterilisation by gas; vapour sterilisation; and sterile filtration, before final chapters analyse depyrogenation; cleanrooms; aseptic processing; media simulation; biological indicators; sterility testing; auditing; and new sterilisation techniques.

Key Features

  • Covers the main sterilisation methods of physical removal, physical alteration and inactivation
  • Includes discussion of medical devices, aseptically filled products and terminally sterilised products
  • Describes bacterial, pyrogenic, and endotoxin risks to devices and products


Pharmaceutical professionals; Quality assurance personnel; Microbiologists


No. of pages:
© Woodhead Publishing 2013
Woodhead Publishing
eBook ISBN:
Hardcover ISBN:

Ratings and Reviews

About the Authors

Tim Sandle Author

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.

Affiliations and Expertise

Bio Products Laboratory, UK