What has happened?

After a development process that stretches back to the beginning of 2018, ISO has published the updated version of the International Standard ISO 10993-17. It has been a mammoth effort, involving over 100 scientists from 20 different countries (including bibra Senior Toxicologist, Chris Waine), and one that the toxicological and medical device worlds have been waiting for with bated breath.

Why is this important?

ISO 10993-17 is the guideline that describes how toxicologists across the globe conduct health risk assessments on medical devices. Crucially, this Standard had not been updated since 2002 and the well-thumbed pages decorating many thousands of toxicologists’ desks had, in truth, ceased to represent the best science available.

Part 17 is one of 23 Standards that make up the ISO 10993 series covering all aspects of the biological evaluation of medical devices. Recent updates to other parts have, for example, introduced in vitro testing for skin irritation and improved the methodology of chemical characterisation based on best analytical practices. It was critical, then, that Part 17 was brought up to date as soon as possible.

So, what’s new..?

For starters, the name of the Standard has been changed to reflect its slightly broader scope. Where the 2002 edition talked of establishing “allowable limits for leachable substances”, the new version is clearly titled “toxicological risk assessment of medical device constituents.” The whole Standard is now placed within the context of biological evaluation, with clear reference to ISO 10993-1 and the rest of the series.

Several terms and concepts have been removed. Gone are “tolerable exposures”, “utilization factors” and “benefit factors”, among others. In fact, even “allowable limits” are no longer mentioned. In comes the “toxicological screening limit”, essentially a Threshold of Toxicological Concern (TTC)> based on the total quantity of extractable/leachable detected in the chemical characterisation. Greater emphasis is placed on the estimation of patient exposure, too, with clear guidance on how to determine this. There are also more specific Uncertainty Factors for specific cases, including difference in routes of administration, duration of exposure and quality of data, bringing this ISO Standard in line with common practice in other sectors.

…and what remains the same?

The science of hazard and risk assessment hasn’t changed. ISO 10993-17 still requires a careful consideration of the available scientific literature, with appropriate Uncertainty Factors applied to a conservative Point of Departure to derive either a Tolerable Intake (TI) for systemic effects or a Tolerable Contact Level (TCL) for local effects. The TI or TCL is then compared to the estimated patient exposure to generate a Margin of Safety. In the absence of suitable data, the TTC approach is still encouraged.

Summary

Bibra has been monitoring these modern developments by regular attendance and presentation at conferences relating to biocompatibility and extractables and leachables assessments for some time. Indeed, where we felt it was appropriate, we had already been using several of these newer concepts in our own medical device assessments. This publication makes these approaches official and marks the start of the modern era in medical device risk assessment.

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