The biological evaluation of medical devices is an important aspect of ensuring that medical devices do not cause harm to the patients using them.

With the release of the ISO-10993-18:2020 guidance[1] (chemical characterization of medical device materials within a risk management process) the importance and priority of the use of chemical characterisation to support the evaluation of a medical device’s health risk has increased.

A key change from the previous version of ISO10993-18 has been the introduction of the AET (analytical evaluation threshold) concept. The AET can be thought of as an identification threshold, analytes detected above this threshold should be identified and quantified to allow toxicological evaluation of chemical species which migrate from materials used in the medical device. Analytes below this threshold are considered (apart from some exceptions known as a cohort of concern compounds) are considered to pose negligible risk to human health, specifically carcinogenic risk.

It is, therefore, important to design the chemical characterisation study with the AET in mind. Several factors can affect the AET for a particular chemical characterisation study for a medical device. These include:

  • Clinical use of the medical device
    • Number of devices used by a patient
    • Length of patient exposure to the medical device
  • The volume of solvent required to extract/cover the medical device
    • Including sample concentration
  • The type of extraction (e.g. exaggerated/exhaustive) – is affected by the length of patient exposure
  • Limit of detection of the analytical technique. This can be affected by:
    • The individual technique
    • The sample introduction technique
  • Analytical uncertainty

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Many of these factors are fixed and cannot be changed to achieve the required AET. Generally, the only factor which is in the analytical chemist can change to ensure the AET is achieved is the volume of solvent used to extract the medical device and/or concentration steps. However, the size/dimensions of the medical device can’t always be changed; thus, the volume of solvent required to completely cover and extract the medical device may also be fixed.

The clinical use of the medical device is fixed, and the duration of contact will dictate if the extraction is exaggerated or exhaustive which can affect the amount of solvent used to extract the medical device. The limit of detection of the analytical techniques is also fixed with a few options to improve detection e.g. injection volume. Therefore, the main factor that is available to the analytical chemist to affect the AET is the amount of sample concentration that is applied to the extracts.

Case Studies

We are producing a series of case studies focusing on various examples of medical devices, looking at some of the challenges and considerations when designing the chemical characterisation study for these devices. As a way of illustrating the variations between various devices, we have scored them in a “top trump” style format. Find the first case study, the femoral stem implant, below.


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