Extractable and leachable testing for medical devices

Medical devices

For a while extractable and leachable testing for medical devices has had a far less thorough set of guidelines and recommendations when compared to medicinal products.  As a simplistic view of medical products these are things that act primarily pharmacologically on the body whilst medical devices primarily act physically.  There are a large number of nuances in what can constitute a medical device or a product.  For those developing devices/products to check with the appropriate regulatory body

The guidance changed for medical devices with the significant changes to ISO 10993-18, the latest version was released in January 2020.  This new version has dramatically increased in size from 17 pages to 66.

The new guidance takes a number of points from the key guidance from the PQRI best practises such as the Analytical evaluation threshold (AET) for the determination of the limits of detection required for the analysis.  There are also a number of other similarities, the choice of solvents being one with the requirement in certain circumstances for a polar, non-polar and a mid-polar extracting solvent.  The guidances do discuss a range of extracting techniques such as reflux, Soxhlet but also more instrument based techniques such as super critical fluid extraction and pressurised solvent extraction to name a couple that are applicable to both devices and products.  One area that is identical between medicinal products and devices is the selection of analytical techniques to identify the extractables.  As no single analytical technique can identify, volatile, semi-volatile non-volatile organic compounds and metals a range of techniques are required.  These include gas chromatography, liquid chromatography both with mass spectrometry and inductively coupled plasma for metals.

Two main areas of divergence are the end points for the extraction study, for medicinal products the end point can be determined when asymptotic levels of extractables have been reached in the extraction study.  For devices there are two end points depending on the duration of contact of the device with the patient.  Short term contact (<24 Hours) requires exaggerated conditions (at least worst case clinical conditions) .  For longer term contact exhaustive extractions are required which require multiple repeat sequential extractions until the last extraction amount is less than 10% of the initial  extraction value.  This should be carried out in a reasonable number of steps.  For all extraction conditions the extractions should not be so harsh as to deform or degrade the material and so produce chemical species that the patient would not be exposed to.

It will be interesting to see if and how the potential ICH Q3E proposed guidance will encompass medicinal products and medical devices in all the varieties.

Andrew Feilden
E&L European Strategic Director

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