Chemical characterization of medical devices (part VI)

Part VI   I need a shortcut! What about certified materials?

Great idea, but what do you mean with certified material, what kind of certification? Indeed, medical devices do get a CE marking which is a certification mark and allows the manufacturer to put the devices into the EEA (European Economic Area). But there is no general certification scheme for materials. Why not?

Probably as the legislation is just mean. Or, maybe, it is not as easy as it seems. Before going into details for some material-related topics and tests, a reminder from the ISO 10993-12 which I intentionally did not mention in a previous part of my series: “Testing shall be performed on the final product, representative samples from the final product, materials processed in the same manner as the final product (see ISO 10993-1), or on appropriate extracts of any of these. The choice of test sample shall be justified.”

In other words: test the final device in exactly the state as you will put it into the market. This includes packaging and especially sterilization in case it will be offered as a sterile medical device. All other choices including representative sample(s), or the sole material will need a sound rationale. And, honestly, to write this rationale could get tricky. I’ll try to explain this on the example of “material processed in the same manner as the final product”. Your supplier delivers a polymeric granulate / compound to you which is processed e.g. via injection molding. The parameters used, e.g. temperature, speed / pressure, etc. can have an influence on the outcome of your process, not only in terms of stability or durability but also in terms of biocompatibility and chemical properties.

How can this be? Polymers are made of monomers which got polymerized; sounds obvious, no? This results in a polymer with some kind of properties, which can fluctuate depending on the initial synthesis as well as on processing steps. I don’t want you to bore you to death with the molar mass distribution like Mn, Mw or Mz, but coming back to the initial aspect: using different parameters in processing steps can lead to the formation of oligomers which have different biological, chemical and technical properties than the initial polymer.

Probably you’re now disappointed but you shouldn’t. You learned that there is no certification scheme for materials in general and that during processing steps it can occur that properties change due to the applied parameters. But now it’s getting better: of course, you benefit from previously performed material-related tests of your supplier. If it was shown that the amount of toxic substances leaching out of or extracted from the material is low to zero, it will give you more confidence in your own process and technical documentation submission. Additionally, having negative test results regarding the base material in regard to the ‘big three’ of the biological endpoints, you would have a better basis for a rationale why you might omit one or more of these or other tests on your final device.

In order to elucidate two aspects: negative results in biological tests are the favorable ones; the ‘big three’ in the field of biocompatibility for medical devices are cytotoxicity, irritation and sensitization tests. The three mentioned ones have to be considered for all medical devices, no matter of type of contact or contact duration. Pay attention, ‘considered’ does not mean to be tested at all times.

In order to bring down to a round figure I would like to mention the USP plastic class testing. Six different classes do exist, the highest (VI) is the one usually used in pharmaceutical applications as well as for medical devices. For this classification the systemic toxicity in mice, the irritation in rabbits and an implantation in rabbits have to be tested. With negative (= favorable) results the requirement of USP plastic class VI are fulfilled. Nevertheless, it is not a certification like one from a Notified Body or other authorities, but a test report from a laboratory. However, purchasing und using such a tested material gives you an advantage in your justifications in your technical documentations or risk analysis. To sum things up: certifications for materials do not exist in general, tested material do exist and might be helpful and worth the surcharge.