WHAT IS THE SIGNIFICANCE of a residue or a mixture of residues on an implantable biomedical device? If I perform chemical characterization of materials, do I need risk assessment? With similar processes, historical performance data of the device can provide a level of assurance. However, with new products and new processes, there is the need for a better understanding not only of the identity of the residue but of the significance of the residue. One of the greatest challenges in chemical characterization is performing adequate assessment of biological or toxicological risks from extractables or chemical residuals that can compromise patient safety. ISO-10993-17 has clearly articulated to the medical device community why and how risk assessments are a part of material biocompatibility [1]. But what is not clear is when and if they are absolutely required.

A Decision-Making Tool
Risk assessment is not new, but has only recently been promulgated by international standards and government agencies as a necessary part of chemical characterization and biocompatibility studies. It is really a tool for decision making that has evolved with time. Toxicological risk assessments have a long history with strong ties to the U.S. FDA, EPA, and OSHA. Risk Assessment is important and absolutely necessary to understand the ultimate biological or toxicological human response to materials and chemical processes. It becomes clear that to understand or predict human response to chemicals or materials, there must be close collaboration between the analytical chemist and the toxicological risk assessor.

Risk assessment is a scientific attempt to identify and estimate the true risks, and is the result of considerations of four primary steps. (1) Hazard Identification: identification of adverse health effects associated with exposure to a specific chemical; (2) Hazard Characterization: determination of the quantitative potency of any adverse effect of a chemical; (3) Exposure Assessment: measurement or prediction of the intake a chemical in terms of magnitude, duration, and frequency of exposure; (4) Risk Characterization: the integration of hazard identification, hazard characterization, and exposure assessment to determine the probability of occurrence and severity of risk to human health from the chemical(s).

Protocols for Complex Data
Those who are accustomed to a standard calling out of a specific procedure to identify or quantify a specific analyte may find themselves in unfamiliar territory with ISO 10993-17. Because toxicological data inherently consists of a wealth of complex variables and because the data and supporting studies for a given substance may vary in quantity and quality, a one-size-fits-all standard is impossible.

Instead, ISO 10993-17 is an ambitious, much needed step to define and document consistent protocols for evaluation of the risk factors for specific leachable substances.

This standard provides a systematic method for assessing complex studies. For example, the modifying factor is derived as the product of various component uncertainty factors. One example of a commonly used uncertainty factor is the factor used in extrapolating the effects of animal studies to humans. If only limited long-term exposure studies were available, a higher uncertainty factor leading to a lower acceptable exposure in the human population would be employed. It is noted in the standard that when this factor is combined with other uncertainty factors, modifying factors may be expected to differ by two orders of magnitude. Uncertainty factors and ultimately, the modifying factors, are derived on a case-by-case basis and are highly dependant on the quality of the toxicological database.