Abstract
During their clinical use, medical devices contact, directly or indirectly, tissue of the person (patient) whose medical condition is being treated or monitored by the device. During contact, substances present in or on the medical device can be leached from the device. Medical devices are chemically characterized to establish the patient's actual exposure to leachables. Establishing actual leachables from implanted methodical devices is problematic as so doing would require sampling of the in vivo environment in which the device is implanted. Thus, leachables from implanted medical devices are estimated by performing extraction studies. Often, such extraction studies use extraction solvents of multiple polarities to establish the device's total extractables profile (all possible extractables at their highest possible levels). As the potential range of extractables' polarities is large, using a small number of extraction solvents with widely different polarities can produce polarity gaps in which an extractable is either not revealed by the selected extraction solvents (an omission gap) or is underestimated in the extraction solvents (a magnitude gap). In either circumstance, the patient's exposure to extractables (as potential leachables) is underestimated. Furthermore, extraction studies that use extraction solvents with polarities outside of the polarity range of in vivo environments are inefficient, as they reveal extractables that cannot possibly be leachables at levels that cannot possibly be achieved during clinical use. After discussing these challenges from a thermodynamic and conceptual perspective, this author proposes that extraction studies for implanted medical devices use extraction solvents whose polarities bracket the polarity of the implanted in vivo environment and that a non-polar solvent never be used for bracketing purposes. To accomplish bracketing, this author introduces the polarity range termed "seminonpolar", establishes the polarity of in vivo environments, and specifies polarity brackets.