Contributors Author bios Introduction

1.Cytotoxicity Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Sandhiya Thamizharasan, Safura Fathima and Krithaksha V.

Introduction ISO 10993-5 Cytotoxicity Detection methods Test by indirect contact Quantitative method Abbreviations References

2. Sensitization Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Sandhiya Thamizharasan and Safura Fathima

Introduction ISO 10993-10 Test methods Guinea pig tests Guinea pig tests and sensitization potency assessment Guinea pig maximization and Buehler tests Open epicutaneous test Advantages and limitations Local lymph node assay The LLNA and sensitization potency assessment Advantages and limitations Human skin-sensitization testing Advantages and limitations Application of test methods in risk assessment Guinea pig tests Local lymph node assay Human repeat-insult patch test Abbreviation References

3. Irritation test Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath and Indumathy Jagadeeswaran

Introduction Selection of animals Test procedure Alternative methods In vitro tests methods for irritation References

4. Material-mediated pyrogenicity Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Sandhiya Thamizharasan and Safura Fathima

Introduction Broad range of pyrogens Tests using fluid extracts Selection of animal species Animal status Animal care and husbandry Size of groups Number of groups Treatment controls Route of exposure Test sample administration Pyrogen tests LAL test Rabbit test: sham test (in vivo) Interpretation of results Monocyte activation test (in vitro test) Procedure of MAT Advantages Abbreviations References

5. Acute systemic toxicity Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath and Indumathy Jagadeeswaran

Introduction Considerations Acute systemic toxicity Selection of animals Animal status Animal care and husbandry Size and number of groups Routes of exposure Dosing Body weight and food/water consumption Clinical observations Clinical pathology Anatomic pathology Evaluation criteria Final report References

6. Repeated-exposure systemic toxicity (subacute, subchronic, and chronic systemic toxicity) Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran and Harini Sriram

Introduction Animal care and husbandry Size and number of groups Routes of exposure Dosing Clinical observations Clinical pathology Anatomic pathology Evaluation criteria Final report References

7. Implantation Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath and Indumathy Jagadeeswaran

Introduction Selection of animals Test procedure References

8. Hemocompatibility Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Krithaksha V., Vinod P. Bhalerao and Sandhiya Thamizharasan

Highlights Introduction Types of devices in contact with blood Characterization of blood interactions Categories of tests and blood interactions Preclinical evaluation of cardiovascular devices and prostheses Advantages and limitations of animal and in vitro testing Laboratory testsdprinciples, scientific basis, and interpretation Evaluation of hemolytic properties of medical devices and their components Hemolysis testingdgeneral considerations Abbreviations References

9. Tests for genotoxicity Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran and Harini Sriram

Introduction Requirements Genotoxicity Example test method: mouse lymphoma mutagenesis assay Evaluation criteria Results Conclusion References

10. Carcinogenicity Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Safura Fathima and Sandhiya Thamizharasan

Introduction Carcinogenicity test-specific considerations Abbreviations References

11. Reproduction toxicity Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Sandhiya Thamizharasan and Safura Fathima

Introduction Principle of the test Description of the method Procedure Data and reporting Abbreviations References

12. Toxicokinetics Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Vinod P. Bhalerao, Sandhiya Thamizharasan, Krithaksha V. and Jayanta Saha

Introduction Principles for design of toxicokinetic studies Guidance on test methods Toxicokinetic study sampling Toxicokinetic study report Guidance on specific types of test Absorption Distribution Metabolism and excretion Abbreviations References

13. Data leverage Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath and Indumathy Jagadeeswaran

Introduction Leverage from literature Leverage from Threshold of Toxicological Concern (TTC) Leverage from reviewed devices Leverage from vendors testing References

14. Chemical characterization Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath, Indumathy Jagadeeswaran, Sandhiya Thamizharasan and Krithaksha V.

Introduction Why characterize materials? Chemical characterization Material characterization Plasticizers Sterilization techniques used for medical devices Corrosion Extractables and leachables Set up a chemical characterization study Conclusion References

15. Biological evaluation report Prakash Srinivasan Timiri Shanmugam, Thamizharasan Sampath and Indumathy Jagadeeswaran

Contents Index