With an ever-increasing emphasis across the medical device industry on chemical characterization via ISO 10993, and the 2020 update to ISO 10993-18, more and more companies are finding themselves required or “encouraged” to perform extractables and leachables testing on medical devices which previously sailed through regulatory hurdles.
For example, EKG Labs has recently been working with multiple clients to develop and execute extractables and/or leachable studies on nasal cannulas.
While nasal cannulas might seem to be lower risk compared to implantable and/or long-term exposure medical devices, the FDA has been asking for more thorough filings due to skin contact and concepts related to inhalation potential of outgassing plasticizers. This heightened focus on nasal cannulas partially comes from the increasing attention to high-flow nasal cannula oxygen therapy as an alternative to mechanical ventilation and other invasive forms of respiratory support for critically ill patients.
A Nasal Cannula Case Study
For one such client, EKG Labs performed an exaggerated extractable study per ISO 10993-18. An exaggerated extractable study is performed to purposely inflate the number or amount of chemical compounds pulled out from the cannula relative to clinical use. In this case, the extraction was performed in a polar (water), mid-polar (ethanol), and non-polar (hexane) solvent in order to capture a wide range of extractable compound chemistries. The extraction was performed at 50°C, a temperature far above human body temperature, for 72 hours.
Extraction solutions were analyzed for volatile compounds by GC-MS direct injection, for semi- and non-volatile compounds by LC-UV-MS, and for elemental impurities by ICP-MS (water extracts only). GC-MS headspace analysis was additionally performed on the water extracts and a direct preparation of the cannula itself. Across all of these methods, we were able to achieve the client’s targeted analytical evaluation threshold (AET) of 1.5 µg/cannula.
Essentially no extractables elements were observed by ICP-MS. There were a number of phthalate fragments observed by LC-MS. The GC-MS analysis represented the most exaggerated conditions of extraction and showed:
- A handful of plasticizers and plasticizer fragments (including DEHP at very high concentration)
- BHT and a similar antioxidant
- An unreacted precursor to nylon
- Some smaller branched alkanes, residuals of PE production
- Palmitic acid (a surfactant) and related compounds
Potential next steps for this project include a targeted extractable study for any compounds flagged by the toxicologist for routine monitoring and/or a leachable study. While hopefully very little would be observed during a leachable study, this can be an important checkbox to include with an FDA submission.
ISO 10993 Testing at EKG Labs
At EKG Labs we specialize in chemical characterization of medical devices and device materials to provide ISO 10993 biocompatibility data for regulatory filings. Our team has years of experience working with diverse pharmaceutical products and a variety of medical device materials.
Our medical device extractables/leachables program is constructed around ISO 10993-12 (sample preparation) and ISO 10993-18 (chemical characterization). We routinely carry out exhaustive extractions (assessed by gravimetric analysis), exaggerated extractions, simulated-use extractions, accelerated aging studies, and leachable studies—all per ISO 10993 guidance.
You can read more EKG case studies here. EKG Labs has also published a general overview of ISO 10993 on our website.
About EKG Labs
EKG Labs is an analytical service provider for the pharmaceutical and medical device industries. Our wide variety of analytical services support product development, regulatory filings, and analytical chemistry investigations.
To find out more about ISO 10993 chemical characterization testing, contact EKG Labs at firstname.lastname@example.org or at 810-354-5229.