Toxicological Considerations in Relation to the Regulatory Safety Evaluation of Medical Devices

Medical devices and their component materials are potential sources of toxins that may produce undesirable local and/or systemic toxic responses when used clinically. The evaluation of toxic responses of medical devices using various toxicological test methods is also called biocompatibility evaluation of medical devices. The evaluation of toxicity (biocompatibility) of medical devices has been a complex task, because the devices are made of a diverse range of materials and have various intended uses, with body contact ranging from transient skin contact to permanent implantation. The safety and effectiveness of medical devices marketed in the United States (USA) is regulated by the Center for Devices and Radiological Health (CDRH) of the US Food and Drug Administration (FDA). The medical devices marketed in the European Union (EU) are required to comply with EU Medical Devices Directive 93/42/EEC, which specifies requirements for safety assessment. There are several national and international standards that address the toxicological evaluation of medical devices. In recent years the FDA—in particular the CDRH—uses and accepts toxicological data generated using the national and international biocompatibility standards to evaluate the safety of medical devices. The EU and Japan (MHLW) also use and accept toxicological data generated using international standards. This chapter is an introduction to a relatively new and rather complicated field in toxicology—the toxicological testing of medical devices. It discusses the toxicological considerations for establishing the safety of medical devices to meet the requirements of regulatory agencies. The guidelines for testing of medical devices are discussed and a general description of the various test procedures given. Developments in the field of biocompatibility regarding international harmonization are also addressed. Keywords: medical devices; biocompatibility of medical devices; toxicity testing of medical devices; regulatory requirements; classification of medical devices; International Standards and Guidelines