In vivo and in vitro testing for the biological safety evaluation of biomaterials and medical devices

Medical devices and the materials they are composed of need to be evaluated for their safety within the context of a risk management process. Safety issues related to toxicity can be evaluated using the ISO 10993 series of international standards for biological evaluation of medical devices. It provides an approach that combines the review and evaluation of existing data from all sources with, where necessary, the selection and application of additional tests, thus enabling a full evaluation to be made of the biological responses to each medical device, relevant to its safety in use. This chapter focuses on the various test methods, both in vitro and in vivo, that can be used for this evaluation. In addition to general in vitro cytotoxicity tests, more specific in vitro tests for genotoxicity, interaction with blood, and irritation are highlighted. Furthermore, in vivo tests for irritation and sensitization, hemocompatibility, genotoxicity, carcinogenicity, implantation, and systemic toxicity are described. Finally, immunotoxicity testing is presented and guidance is provided on how to apply the various in vitro and in vivo test methods for the biological evaluation of medical devices that contain or are composed of nanomaterials.