Why chemical characterization is the best way to assess patient risk

Although chemical characterization is not a fool-proof technique, Christopher Pohl, associate toxicologist, Nelson Labs explains why this method is still considered to be the best and strongest way to assess patient risk.

Everyone is very familiar with the phrase when buying a house: All that really matters are three things - location, location, and location. This same principle applies to extractables and leachables chemistry analysis – the three things that truly matter are identification, identification, and identification.

The greatest growth in the past ten years in demonstrating the safety of medical devices and container closure systems for drugs has been using analytical chemistry to determine what chemicals can leach from the device and what the patient is exposed to during its intended use. The use of analytical chemistry can significantly improve the safety of medical devices by allowing for the assessment of long-term endpoints which are very difficult to assess using traditional animal models.

That being said, analytical chemistry is only as good as the identification of the compounds that are detected. If, for instance, the compounds cannot be identified, the hazards posed by the chemicals cannot be known. Also, if compounds are misidentified, it could cost the company thousands of dollars in mitigating hazards that are not real, or even worse, luring the company into thinking that a device does not pose a hazard when in fact there is a significant risk introduced to the patient. These examples are not just theoretical; many of these have been experienced recently in the medical industry.

For example, a medical device manufacturer was testing a new device. Their first step to determine if the device was safe was to perform an extractables and leachables study followed by a toxicological risk assessment. When the analytical chemistry was completed, there was a set of compounds tentatively identified as tetrachlorodibenzo-p-dioxin. P-dioxin is a carcinogen, a mutagen and a teratogen and is not acceptable to have in a medical device at any level. Detecting this compound was controversial, as it was not known how it got onto the finished device. To have a compound like p-dioxin being detected during verification could potentially scrap the entire project, and so additional identification work was deemed necessary to confirm the identity of the chemical compound. The additional work, however, cost in excess of ten thousand dollars and it took two to three months for the actual identification to be confirmed. In the end, it turned out that the substance was not p-dioxin, but was identified as chlorobenzoic acid instead, which has a much higher tolerable exposure.

On the flip side, as indicated above, there have been cases where a compound was identified as non-hazardous when, in actuality, it is hazardous. This is the most dangerous of situations, as this is the scenario where patients, clinicians, and caregivers can be exposed to toxic and even carcinogenic chemicals without even knowing about it. In some instances, this can occur when chemicals are lower than the detectable limit of the analytical test. 

Through being aware of possible hindrances, chemical characterization is still the best and strongest option to assess risks to patients and the people that we are trying to help during their time of need when conducted correctly. Chemistry plays a crucial role in helping to characterize and mitigate the biocompatibility, systemic toxicity and carcinogenicity risks that would be difficult to detect and identify otherwise.