Biocompatibility Protocols for Medical Devices and Materials

Prakash Srinivasan Timiri Shanmugam, PhD, is currently a Senior Toxicologist at Avanos Medical, Inc. in Alpharetta, Georgia. He was previously contracted as an SME–Biocompatibility at Baxter International, Inc. in Round Lake, IL, United States, and at Johnson & Johnson Medical Device Sector. He has an MSc and a PhD in the specialization of Pharmacology and Toxicology with Chemistry (interdisciplinary) from the University of Madras, Tamil Nadu, and completed his postdoctoral research at Tulane University and LSUHSC-Shreveport, Louisiana. He has authored 5 books, contributed several book chapters, and published research articles in various peer-reviewed international journals and conference proceedings/abstracts. Thamizharasan Sampath, PhD, PGDCR, is currently Dean of Research and Professor of Pharmacology & Toxicology at the University of Health Sciences (SBIMS), Raipur, CG, India. He has done his MS and PhD specializing in pharmacology under the faculty of medicine from the Post Graduate Institute of Basic Medical Sciences, University of Madras, and also did his Postgraduate diploma in clinical research at State University. He has 17 years of teaching and research experience. His research areas include cancer pharmacology, clinical research, neurotoxicology, nutraceuticals, reproductive toxicology, endocrine pharmacology, phytopharmacology, molecular pharmacology, drug design, and drug discovery. He has published more than 60 research articles in national and international indexed journals and is the author of the book Bamboo - The Golden seed and has also contributed more than 20 book chapters. He has received many awards from various central organizations for his outstanding research and contribution in the field of medicine. He serves as a Chief Editor, Editorial Board Member, and Reviewer in many medical journals. He is a member of Institutional Research Ethics Committee, Animal Ethics Committee, Indian Pharmacological Society, and UNESCO Bioethics Committee. Indumathy Jagadeeswaran, PhD, is currently working as a Senior Research Associate in the Department of Pediatrics at UT Southwestern Medical Center, Dallas, Texas, United States. She has an MS in Biotechnology with Biochemistry (interdisciplinary) and PhD in Medical Physiology from the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) in Pondicherry, India. She has been working in the field of physiology since 2011 and has completed her postdoctoral training from prestigious institutes including the UT Southwestern Medical Center, Dallas, Texas. She has editorial experience including being an Associate Editor (2014–2017) for a peer-reviewed international journal and is presently a Peer-Review Member of the Scientific Committee and Society. She has contributed book chapters on regulatory standards and has also published research articles in various peer-reviewed international journals.

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