While the safety assessment (“biocompatibility”) of medical devices has been focused on issues of local tissue tolerance (irritation, sensitization, cytotoxicity) and selected quantal effects (genotoxicity and acute lethality) since first being regulated in the late 1950s, this has changed as devices assumed a much more important role in healthcare and became more complex in both composition and in their design and operation. • As the duration (and rate) of exposure to moieties released from a device are most frequently different (longer) than what available data speaks to, transformation across tissue is required.