ISO 10993-17:2023 assessment of extractables and leachables data: tolerable intake, worst-case exposure and margin of safety, reviewed by a board-certified toxicologist.
A toxicological risk assessment (TRA) establishes whether the chemical constituents a medical device can release are present at levels that could harm a patient. It is carried out under ISO 10993-17:2023 and takes the results of chemical characterization, the extractables and leachables testing described in ISO 10993-18, as its starting point.
Chemistry shows what is there and how much; the assessment shows whether that amount matters. For each constituent above the toxicological screening limit, a tolerable intake is derived from the available toxicity data, a worst-case exposure is estimated from the amount measured and the way the device is used, and the two are compared as a margin of safety.
The conclusions feed the device’s biocompatibility evaluation, where they can be used as evidence for endpoints such as systemic toxicity, genotoxicity and carcinogenicity. Groenakker carries out the assessment on its own or together with the chemistry as a ChemTox™ extractables and leachables study.
A toxicological risk assessment is only as sound as the chemistry behind it and the reasoning recorded in it. Each tolerable intake in a Groenakker report is shown with the study it came from and the factors applied, so a reviewer can follow the value back to its source.
The conclusions are written to be cited. Each one names the endpoint it addresses, so your biological evaluation report can reference it directly, and every assessment is reviewed by a board-certified toxicologist (DABT).
Included
Within a ChemTox™ study the data analysis and toxicological review take an estimated one to two weeks, and reporting about a further week. A standalone assessment takes an estimated two to three weeks from receipt of complete chemistry data.
Phase I
Scope and data review
01 – Agree the scope: the device, its contact type and duration, and the chemistry data to be assessed.
02 – Groenakker reviews the chemical characterization report and confirms it identifies and quantifies constituents to the level the assessment needs.
Phase II
Screening
03 – Reported constituents are compared with the toxicological screening limit; those above it are carried forward.
04 – Constituents are screened against EU MDR CMR substances and cohort-of-concern compounds.
Phase III
Assessment
05ᵃ – Toxicity data are gathered and a tolerable intake is derived for each constituent carried forward.
05ᵇ – Worst-case exposure is estimated and a margin of safety is calculated for each constituent.
Phase IV
Reporting
06 – The report is reviewed by a board-certified toxicologist (DABT) and issued to the client.
The 2023 edition of ISO 10993-17 sets out the assessment as a sequence. Constituents reported by the chemistry are first compared with the toxicological screening limit. Those above it are assessed one by one, and each assessment ends in a margin of safety that can be traced back to the data it came from.
The amount of a constituent a patient can be exposed to without appreciable harm.
How much of the constituent a patient could receive from the device.
The comparison that gives the conclusion for each constituent.
Not every extractable has a published toxicity study. Where data are missing, the assessment draws on:
It is the assessment of whether the chemical constituents a device can release could harm a patient at the amounts measured. Under ISO 10993-17:2023, each constituent of concern is given a tolerable intake, the worst-case patient exposure is estimated, and the two are compared as a margin of safety.
ISO 10993-17 is the part of the ISO 10993 series that covers the toxicological risk assessment of medical device constituents. The current edition, ISO 10993-17:2023, sets out how to screen constituents, derive tolerable intakes, estimate exposure and calculate a margin of safety.
No. It is a documented assessment, not a laboratory test. It uses the results of chemical characterization testing under ISO 10993-18, together with published and predicted toxicity data.
A chemical characterization report that identifies and quantifies the extractable or leachable constituents, a description of the device, its contact type and duration, the number of devices a patient may be exposed to, and the intended patient population.
It can address some endpoints. ISO 10993-1 allows chemical characterization with a toxicological risk assessment to be used as evidence for endpoints such as systemic toxicity, genotoxicity and carcinogenicity, where the data support it. Whether that evidence is sufficient for a given device is decided in the biological evaluation.
The toxicological screening limit (TSL) is a cumulative exposure below which a constituent is not expected to pose a toxicological concern and does not need an individual assessment. Constituents above it are carried forward.
A margin of safety below 1 means the worst-case estimate exceeds the tolerable intake, so the constituent needs further work. That can mean refining the exposure estimate with more realistic data, further chemistry, a targeted biological test, or a change to the material or process.
Every Groenakker toxicological risk assessment is reviewed by a board-certified toxicologist (DABT).
Within a ChemTox™ study, data analysis and toxicological review take an estimated one to two weeks once the chemistry is complete, and reporting about a further week. A standalone assessment on chemistry data you already hold takes an estimated two to three weeks from receipt of complete data.
