Duration of use - repeat use


Hello everyone,

We have got Biocompatibility Clarification Question (510k submission) related to the categorization of our device. Our system is an active, non-invasive therapeutic device. The device produces an electromagnetic field that interacts with the tissues of the human body. The parts in direct contact with the patient body, namely intact skin, are applicator covers. These applicator covers are made of PC ABS, RAL 7035 + UV stabilizer. Biocompatibility studies were carried out in the past (cytotoxicity, irritation and sensitization).
When we consider the nature and method of therapy application, the worst case scenario of device (applicator housing) contact with the patient is a situation where the patient undergoes a total of 29 therapy sessions every working day over a period of 6 weeks (29 contacts over 39 days).
The worst case scenario is as follows:

- 18 minutes is considered as a possible time of finding the patient's motor threshold before the therapy application,
- 18 minutes of OCD therapy session time and an additional time reserve of approx. 20% of the total time for setting up the device, fixing the applicator in the arm and positioning the patient, etc.

In total we get a patient contact time of approx. 44 minutes per one day of therapy. If we consider the therapy would be applied every consequent day (not only on a working day) the total contact time of the patient with the applied part of the device is 44 minutes x 29 therapies which is approx. 22 hours in total.
This cumulative exposure time corresponds to a classification according to Annex A of 10993-1 standard in category A - limited patient contact time for less than 24 hours.

The CDRH expert does not agree with calculated duration, stating that:

For biocompatibility considerations, CDRH does not support adding up minutes or hours to determine device categorization (duration of use) for devices with repeat use. If chemicals are leached from the device, those chemicals can bioaccumulate such that with repeat device use, higher levels of chemicals may be present in amounts that could result in toxicity. Thus, based on the proposed intended us, the system should be categorized as an intact skin contacting device with long-term/permanent (> 30 days) contact.

The FDA Guidance for biological evaluation defines the limited duration as:
Limited exposure: “Medical devices whose cumulative sum of single, multiple, or repeated duration of contact is up to 24 hours.”
[SOURCE: ISO 10993-1:2018, Clause 5.3.1 a)]

I think that the approach of cumulative sum is the correct one but I also understand his point of view ... It is hard to find the correct defence.


Quite Involved in Discussions
What the FDA reviewer told you is consistent with what I've seen personally. I doubt that you will be able to persuade them on this point because it's consistent with the FDA's viewpoint on this topic.

However, for intact skin contacting devices the biological endpoints you need to evaluate are the same for short term/long term. Even if it is permanent/long term contact, you shouldn't have to do additional testing, unless the test analysis was not sufficient for the contact duration. Have you looked at the testing to see if it can be applied for long term/permanent contact? I would reach out to the test lab you worked with to ask if they can do an evaluation of the data you have in consideration of the longer contact duration.

IMO the contact duration is really only important for defining the endpoints that need to be tested. If you have testing that is sufficient to show safety for the permanent/long term contact duration, I don't think I'd fight this battle.


But by this logic, almost every medical device intended for repeated use would be classified as long term, which I have not encountered in practice. At least not in the EU. So far, no one has disputed the classification, including NBs under the MDR. And most of out MDs are just skin contacting devices which we classified as limited. So what approach is the correct one. The classification is the first step and it is performed based on the MDs intended use. The risk of degradation and toxicity of the material should be evaluated if the risk based approach identify this danger, at least we did it this way.

Anyway, thanks for the answer. Unfortunately, the testing conditions were not set up to comply long term condition contact. The extraction time for cytotoxicity was 24h at 37°C for example. For GMPT test, the extracts were prepared at 50 ºC for 72 h which could be fine.


Quite Involved in Discussions
There is a difference between the contact duration for biocompatibility and the contact duration for device classification, so maybe that's why this hasn't come up before with your NB. When determining Class I, Class IIa, etc, your device would still be considered short term. I've only ever heard the concept of "cumulative exposure" in reference to biocompatibility. FWIW, I also work with a device that is intended to be used on a regular basis for years...and our duration of contact for biocomp is permanent/long term even though there are single use components.

The "limited use" of each individual device does matter, because obviously cumulative exposure of a device in 10 min intervals is different from a truly permanent device. Do you have extractable/leachable testing or any other material characterization testing that can help prove that the material does not degrade or leach anything over the duration of time that it's used?

I would still ask your test lab for help in justifying. YMMV based on their expertise but they should be able to advise on whether there's any justification based on the testing you do have. The route I would try to take is accepting the classification as long term, but justifying that the testing you have is sufficient evidence based on your use case. I'm not a biocomp expert in any way so I don't have much insight on how to justify from a technical perspective, but that would be my starting point.
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