Where does Contact begin for Biocompatability?



Dear cove experts,

I am in the process of trying to ensure that our new CPAP prototype is certifiably biocompatible for CE marking, but I am having trouble figuring out what needs to be biocompatible and what testing needs to be done.

The biggest question I have is based on the contact of the device. We have air streaming from the walled oxygen and the compressors through the internal tubing, filters, and etc inside the device to the external humidifier then to the tubing, then to the patient interface. From ISO 10992-1, I classified the patient interface (which is not currently involved in our CE marking process, we may recommend buying a CE marked one already) as having prolonged contact with the mucosal membranes.

The air, oxygen, or a combination of the two pass a long way before they enter the patient's lungs. Would everything need to be biocompatability tested from the air compressor to the filters to the external tubing or would just the external parts of the device (tubing and humidifier) that are disinfected regularly need to be certified biocompatable. Also, would the same cytotoxicity, sensitization, and irritation or intracutaneous reactivity testing be required for each component (filter, regulator, tubing, humidifier, etc.)?

Also, why is ISO 10993-10 "Tests for irritation and delayed-type hypersensitivity" not on the on the harmonized standards list?

Thanks in advance,

Elsmar Forum Sponsor


I don't think the particular question is answered adequately by existing standards and guidances. The ISO 10993 standard-series of course does say that it's non-applicable to non-patient-contact devices, but that's not the same question.

I used to think that the requirement was that only that part of a medical device that would, or plausibly could, have patient (or in some cases, clinician) contact needed to be biocompatible. For me, anyway, that approach is logical.

I recently was informed by a US FDA examiner, though, that their view (or at least, that particular examiner's) is that if any part of a device is required to be biocompatible, the entire device--including non patient contact elements, I guess including fully enclosed, internal components if such are present--must be biocompatible.

That of course isn't definitive for the EU. I don't know of a definitive answer for EU...maybe someone else does.
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Contact to the healthy skin is the first level of the contact for bio.
The air, O2 or the combination of other gases are not a part of your device. Your device assists in its delivery. The purity of these may not be compromised by your device in terms of contaminating or adding particulate matter, and your design and material selection must be addressing this.


Thanks for you help.

I will just conduct the cytotoxicity, sensitization, and irritation or intracutaneous reactivity biocompatibility tests on the humidifier, connectors, and tubing then.

As for the rest, I will have to make sure everything is ROHS compliant (along with the rest of the device), and free of DEHP, BPA, and latex.

Take care,


Ronen E

Problem Solver

In my opinion, there's a significant grey area WRT this issue.

The approach "only direct contact must be investigated" is detached from 10993 itself. For instance, one of the contact categories is "externally communicating, blood path, indirect". it's intended for all sorts of administration tubing (among aother things), and accounts for the possible conveyance of substances from components not-directly contacting the patient, by means of fluid media.

The opposite approach of "everything must be compatible" is ridiculous / outrageous. If an eletrical device has a fully enclosed circuitry that is detached from any applied parts in terms of substance transfer, does that circutry have to be biocompatible to the same level as the applied part?... I believe the majority of MEE on the market would fail such a requirement.

As with all things grey, a reasonable and fairly-efficient approach can be based on risk management. For instance, if you have a set of components behind a filter in a flow path (with known filter performance and reliability characteristics), there's not much point in testing for stuff that won't go past the filter. You probably need to start off with a detailed, structured analysis along the flow path, identifying the possible concerns and their sources, then evaluate the risks in terms of amounts and likelyhood of anything ending up in direct contact with a patient tissue. once you've identified the hazards, focus on those with significant risk and implement appropriate mitigation means. Back to the filter example, such means may make actual biocompatibility testing redundant in some cases. In case of doubt, you could consult an expert toxicologist (such as those working for any respectable biocompatibility test house), to frame those risks that need actual testing. For some of the lower risks, a documented opinion from such toxicologist may suffice.

This issue is not unique to you, about every CPAP device developer had to deal with it at some point. If you go to one of the big test houses, I guess that they will already have some relevant experience.

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