Implant and device manufacturers are increasingly facing the challenge of proving that their products are safe and biocompatible, and that they will perform as expected. Biocompatibility and performance of medical devices provides an essential guide to the performance analysis of these vital devices.
Part one introduces the key concepts and challenges faced in relation to biocompatibility in medical devices, with consideration of biological safety evaluation planning and biomechanical and biochemical compatibility in innovative biomaterials. Part two goes on to discuss the evaluation and characterisation of biocompatibility in medical devices. Topics covered include material and chemical characterisation, allowable limits for toxic leachables, in vivo and in vitro testing and blood compatibility assessment. Testing and interpreting medical device performance is the focus of part three, with chapters describing preclinical performance studies for bone, dental and soft tissue implants, and mechanical testing of soft and hard tissue implants. Part four provides information on the regulation of medical devices in the European Union, Japan and China, and the book concludes with part five, a review of histopathology principles for biocompatibility and performance studies.
With its distinguished editor and international team of expert contributors, Biocompatibility and performance of medical devices is a vital tool for all those involved in the research, design, production and application of medical devices, including research directors, production companies and medical regulatory agencies, as well as industry professionals and academics.
- Examines the key concepts and challenges faced in relation to biocompatibility in medical devices
- Discusses evaluation and characterisation issues, including material and chemical characterization, allowable limits for toxic leachables, in vivo and in vitro testing, and blood compatibility assessment
- Delivers a comprehensive overview of testing and interpreting medical device performance
Part one introduces the key concepts and challenges faced in relation to biocompatibility in medical devices, with consideration of biological safety evaluation planning and biomechanical and biochemical compatibility in innovative biomaterials. Part two goes on to discuss the evaluation and characterisation of biocompatibility in medical devices. Topics covered include material and chemical characterisation, allowable limits for toxic leachables, in vivo and in vitro testing and blood compatibility assessment. Testing and interpreting medical device performance is the focus of part three, with chapters describing preclinical performance studies for bone, dental and soft tissue implants, and mechanical testing of soft and hard tissue implants. Part four provides information on the regulation of medical devices in the European Union, Japan and China, and the book concludes with part five, a review of histopathology principles for biocompatibility and performance studies.
With its distinguished editor and international team of expert contributors, Biocompatibility and performance of medical devices is a vital tool for all those involved in the research, design, production and application of medical devices, including research directors, production companies and medical regulatory agencies, as well as industry professionals and academics.
- Examines the key concepts and challenges faced in relation to biocompatibility in medical devices
- Discusses evaluation and characterisation issues, including material and chemical characterization, allowable limits for toxic leachables, in vivo and in vitro testing, and blood compatibility assessment
- Delivers a comprehensive overview of testing and interpreting medical device performance
Table of Contents
Contributor contact detailsWoodhead Publishing Series in Biomaterials
Foreword
Introduction
Dedication
Part I: Introduction to biocompatibility in medical devices
Chapter 1: Concepts in biocompatibility: new biomaterials, new paradigms and new testing regimes
Abstract:
1.1 Introduction: traditional biomaterials and biocompatibility test procedures
1.2 The evolution from implantable medical devices to regenerative medicine and bionanotechnology
1.3 New concepts and definitions for biocompatibility
1.4 A proposed conceptual framework for new biocompatibility concepts and testing regimes
1.5 Conclusions and future trends
Chapter 2: Challenges in biocompatibility and failure of biomaterials
Abstract:
2.1 Introduction
2.2 Concept of biocompatibility
2.3 Examples of device recalls or alerts during the last decade in which biocompatibility issues were considered
2.4 Challenges in biocompatibility evaluation
2.5 Conclusion
Chapter 3: Biological safety evaluation planning of biomaterials
Abstract:
3.1 Introduction
3.2 The fundamentals of safety evaluation planning
3.3 Safety evaluation planning for biomaterials
3.4 Developing and documenting plans
3.5 Using safety evaluations
3.6 Conclusion
Chapter 4: Biomechanical and biochemical compatibility in innovative biomaterials
Abstract:
4.1 Introduction
4.2 Selection of biomaterials
4.3 Three generations of biomedical materials
4.4 State-of-the-art development
4.5 Future trends
4.6 Conclusion
Part II: Evaluation and characterisation of biocompatibility in medical devices
Chapter 5: Material and chemical characterization for the biological evaluation of medical device biocompatibility
Abstract:
5.1 Introduction
5.2 Background
5.3 Requirements of ISO 10993
5.4 Characterization of materials
5.5 Chemical characterization of extracts
5.6 Using chemical and material characterization to demonstrate equivalency
5.7 Acceptance criteria for equivalency
5.8 Risk assessment of extracts
5.9 Conclusion and future trends
Chapter 6: Allowable limits for toxic leachables: practical use of ISO 10993-17 standard
Abstract:
6.1 Introduction
6.2 Process for setting tolerable intake (TI) values for compounds released from medical device materials
6.3 Derivation of non-cancer TI values
6.4 Derivation of cancer-based TI values
6.5 Derivation of TI values for local effects
6.6 Other issues to consider
6.7 Conclusion
Chapter 7: In vivo and in vitro testing for the biological safety evaluation of biomaterials and medical devices
Abstract:
7.1 Introduction
7.2 Pre-testing considerations
7.3 Sample preparation
7.4 In vitro testing
7.5 In vivo testing
7.6 Conclusion
Chapter 8: Practical approach to blood compatibility assessments: general considerations and standards
Abstract:
8.1 Introduction
8.2 Background: blood composition
8.3 Critical distinguishing factors presented by blood-contacting medical devices
8.4 Responses in fluid blood in contact with medical devices
8.5 Responses by materials, or upon their surfaces, in contact with blood
8.6 Assessing hemocompatibility according to international standards
8.8 Sources of further information and advice
Chapter 9: Medical device biocompatibility evaluation: an industry perspective
Abstract:
9.1 Introduction
9.2 Developing a biological evaluation plan
9.3 Implementing a biological evaluation plan
9.4 Biological safety testing
9.5 Creating a biological evaluation report
9.6 Conclusion and future trends
9.7 Sources of further information and advice
9.9 Appendix: example of a material component biological evaluation report template
1.0 Introduction
2.0 Chemical characterization
3.0 Manufacturing processing
4.0 Tissue contact
5.0 Evaluation of ISO 10993-1 compliance
6.0 Discussion
7.0 Conclusions
Chapter 10: Case study: overcoming negative test results during manufacture
Abstract:
10.1 Introduction
10.2 Cardio Medical: a fictitious case study
10.3.The biological safety program
10.4.Extractables and leachables
10.5 Controlling risk at the manufacturing level
10.6 Sterilization residuals
10.7 Conclusion
Chapter 11: Methods for the characterisation and evaluation of drug-device combination products
Abstract:
11.1 Introduction to combination products
11.2 Combination product regulation
11.3 Demonstrating safety and efficacy of combination products
11.4 Pre-clinical testing of combination products
11.5 Aspects to consider in the manufacture of combination products
11.6 Clinical studies for combination products
11.7 Conclusion and future trends
Part III: Testing and interpreting the performance of medical devices
Chapter 12: Methods and interpretation of performance studies for bone implants
Abstract:
12.1 Introduction
12.2 Definitions
12.3 Scope
12.4 Principles for the selection of an in vivo model to evaluate performance of bone implants
12.5 Designing a study to evaluate performance of bone implants
12.6 Selection of reference products and controls
12.7 Osteoinductive and osteogenic performances
12.8 In vitro limitations
12.9 Fracture repair models
12.10 Spinal fusion models
12.11 Cylindrical defect models
12.12 Segmental defect models
12.13 Antimicrobial performances of implants
12.14 Bioabsorbable and biodegradable materials
12.15 Bone debris interaction with implant performance
12.16 Conclusion
Chapter 13: Methods and interpretation of performance studies for dental implants
Abstract:
13.1 Introduction and definitions
13.2 Importance of performance evaluation studies for dental implants
13.3 Experimental design of a performance trial for dental implants
13.4 Choice of model
13.5 Statistical power calculation and analysis
13.6 Analysis
13.7 Translation from animal studies to human clinical trials
13.8 Acknowledgments
Chapter 14: Non-clinical functional evaluation of medical devices: general recommendations and examples for soft tissue implants
Abstract:
14.1 Introduction and definitions
14.2 The purpose of functional studies
14.3 Standards and documentation
14.4 How to design a functional study
14.5 Combining non-clinical functional studies with requirements of safety standards
14.6 Conclusion
Chapter 15: Mechanical testing for soft and hard tissue implants
Abstract:
15.1 Introduction
15.2 Principles of setting up a mechanical test
15.3 Implant-specific mechanical performance testing
15.4 Advanced therapy products (ATPs) - cartilage
15.5 Conclusion and future trends
15.6 Sources of further information and advice
Part IV: International regulation of medical devices
Chapter 16: Biological evaluation and regulation of medical devices in the European Union
Abstract:
16.1 Introduction
16.2 The regulatory and legislative framework
16.3 Essential requirements
16.4 Presumption of conformity
16.5 Using the EN ISO 10993 series of standards to meet the essential requirements
16.6 The notified body
16.7 Common pitfalls in biological evaluations
16.8 Managing positive results in the biological safety assessment
16.9 Presenting the biological evaluation within the technical file
16.10 Conclusion
16.11 Sources of further information and advice
16.12 Appendix: model content of the biological evaluation submission
Chapter 17: Biological evaluation and regulation of medical devices in Japan
Abstract:
17.1 Introduction
17.2 Outline of biological safety testing in Japan
17.3 Biological safety tests
17.4 Relationship and comparison between the International Organization for Standardization (ISO) standard and American Society for Testing and Materials (ASTM) standard
17.5 Relationship between classification, examination, and certification in Japan
17.6 Outline of the medical device Good Laboratory Practice (GLP)
17.7 Conclusion
Chapter 18: Medical device regulations in China
Abstract:
18.1 Introduction
18.2 Interpretation of ISO 10993 and additional State Food and Drug Administration (SFDA) requirements
18.3 Major professional bodies
Part V: Histopathology principles for biocompatibility and performance studies
Chapter 19: Microscopic and ultrastructural pathology in medical devices
Abstract:
19.1 Introduction
19.2 Morphologic assessment in the safety studies of biomaterials and medical devices
19.3 Assessment of the performance of biomaterials and medical devices
19.4 Processing and sectioning of specimens
19.5 Staining recommendations
19.6 Qualitative and quantitative pathology used in the evaluation of biomaterials and medical devices
19.7 Ultrastructural pathology
19.8 Morphologic assessment of ocular medical devices
19.9 Conclusion
19.10 Acknowledgments
Index
Authors
Boutrand, Jean-PierreJean-Pierre Boutrand is General Manager and Scientific Director for the European division of NAMSA (the world leading medical device evaluation company). Dr Boutrand has been involved in more than 100 public presentations and publications on topics related to medical device evaluation and is registered as an expert on the biological safety of medical devices for ANSM (the French agency for the safety of health products).
