Biocompatibility on aged devices


Hi there,

Did anybody ever test biocompatibility specifically on aged devices? Iso 10993-1 does not say anything about that, however the question came up during our shelf-life Evaluation and i am considering doing it (e.g. initially a chemical characterization of both aged and non-aged device and then compare leachables profile. Then, if significantly different leachables profile conduct biological testing).
One question that comes up now is if accelarated aging would be appopriate, or if we would have to use real-time aged products (end of shelf life).




Involved In Discussions
Accelerated agging is not apporite since heat can evaporate chemicals might cause toxicity. simple example EtO. Most of the cases manufacturing aids causes toxicity.

You can plan for real time agging products.


Hi all,
I am still stuck with this Topic. I did an E&L study on aged vs non-aged devices, but the results are disappointing, since i get a lot of "unidentified" leachables and can't really compare the two test items.
I am currently considering doing a paper-based Evaluation regarding the stability and possible degradation of all the materials used in the device, but i am not sure where to gather data for this.
I really want to avoid doing all the biological tests again on aged devices.
Anybody got any ideas?




Super Moderator

your initial plan to compare E&L profiles of aged vs. non-aged devices sounds reasonable and justified in line with ISO 10993-1:2018. Since you have performed a comparative study, the exact chemical nature of the compounds related to your leachables profile is of minor importance, as long as the same pattern/fingerprint can be observed for the aged product in comparison the non-aged product. If you have detected leachables in the aged product that are different in quantity and/or chemical nature - well then you will have to evaluate these E&L's, either through ISO 10993-17, or by further studies.

In any case, you may consider performing a cytotoxicity test according to ISO 10993-5 both on the aged and non-aged devices, respectively: the test is fast and provides a very sensitive biological endpoint and thus, gives you a first indication whether you might have to deal with toxic degradation products.

Some more items to consider:
  • Have you aged your product in its final packaging? If yes, can you exclude degradation products migrating to your product out of the packaging materials?
  • Are your materials reported in the literature to be susceptible to degradation, or reported to be stable?
  • Is your product (terminally) sterilized? If yes, have you excluded that sterilization plays are role in your differing E&L profiles? Is there any other (subtle) manufacturing process difference between your sample groups, that may have an impact?
  • E&L analysis method(s): which one(s) did you actually use and how did you determine its/their appropriateness?



Regulatory Affairs
Can we skip any of the below mentioned test, for sutures? (Ref. ISO 10993-1:2018)

Irritiation or Intracutaneous Reacitivity
Acute Systemic Toxicity
Sub-acute toxicity
Sub-chronic toxicity
Chronic toxicity
Implantation effects
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