Sterile Disposable Cardiac Guidewire 3yr Real Time Sterility Failure When Confirming Accelerated Aging / Labeling


Hi! I am new so please bear with me :)
A real-time study of 3yrs completed recently to confirm the results of an accelerated aging study. The sterile disposable single packaged device is 510(k) cleared and CE marked, labeled with 3yr shelf-life. The first real-time samples unfortunately were evaluated at the 3yr real-time timepoint and 4/58 exhibited test failure (dye penetration / perforation of foil.) Most likely due the cap damaging the seal (sterile barrier) which could occur during the transport simulation prior to placing devices on real-time study 3-yrs ago. The drop height sequence was 970 mm, part of standard testing (prior to placing the devices on test.) No field complaints noted in the 3yrs of displaced caps or torn packaging, etc. The company is conducting studies on a new pouch however that takes time.

The initial accelerated aging study demonstrated the sterile barrier was suitable however the real-time (pulled at 3-yrs) testing failed. Of course there is a risk of non-sterile product distributed over the prior 3yrs, and there is a new packaging evaluated due to the observed real-time 3yr packaging failures. The company believes that the shake test (per ISTA 2a) and transport simulation process (prior to placing on test) contributed to the cap of the guidewire dispenser damaging the pouch seal seam. There were no observed failures originally during the accelerated aging study submitted to the 510(k) 3-yrs ago.

In addition to what to do with remaining devices in the field, the question is how to share the pouch integrity issue with FDA and then if the new packaging (once validated and accelerated aging study is acceptable) is this a new 510(k) or LTF?

Any help appreciated! The device is also distributed in the EU.



Super Moderator
In order to decide whether any field action is warranted you may want to consider the following points among others:

1) Substantiate/Refute your suspected root cause:
"Most likely due the cap damaging the seal (sterile barrier) which could occur during the transport simulation prior to placing devices on real-time study 3-yrs ago.",

by e.g. inspecting devices that have undergone transport simulation at timepoint = 0. Is there anything noteworthy different about the 4 failed samples, compared to the 54 other samples? (E.g. too weak seals, which might be verified by peel test done on remaining intact seals)

Just be aware that in case you confirm packaging performance being the root cause, you will have to proceed your investigation whether you are still in a position to defend your transport simulation result.

2) Did you formally risk assess your validation failure? With regards to (the absence of) potentially related complaints: sterility failures may be hard to detect in the field. So a lack of complaint is not sufficient to argue that there are no issues in the field.

3) ISO 11607-1:2019, section 8.1:
NOTE 2 Stability testing and performance testing are separate entities. Performance testing evaluates the interaction between the packaging system and the products in response to the stresses imposed by the manufacturing and sterilization processes and the handling, storage and shipping environment

You may want to consider this note in future validation.



Forum Moderator
My comments/questions are from a reliability perspective. I have no background in the medical/regulatory aspects.

When using ALT (Accelerated Life Testing) it is a good practice to use the lower confidence limits as a worst case scenario to predict real time performance. When performing the ALT testing, did you use multiple stress levels or a single level? Good practice is to use multiple stress levels. Has your acceleration model (e.g., Arrhenius, etc.) been validated?


Super Moderator
@Miner: fortunately, for accelerated stability testing of sterile barrier systems, there is a quite specific standardised approach per ASTM1980 that is accepted by medical-device regulators worldwide.
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