Sterilizing media filter 0.2 micrometer by autoclave

integrity test for media filter 0.2 micro was failed after filtration. what are causes probability for this failed, note that the filter has been sterilized by autoclave without housing?

By the information that you give in your question, one of the potential root cause for the failure could be that the sterilization of the filter compromised its integrity.

These are some recommendations for your investigation and how to support whether or not this could be the probable root cause of the integrity test failure:

  • Confirm that the certificate or any technifal document of the filter gives you the confidence that the filter design is compatible with growth medium filtration.

  • Confirm that the fiiltration parameters were met, as indicated by filter technical documen (if you have this filtration process validated, then make sure the filtration process met validated parameters). If differencial pressure is too high, because of media fill being less fluent, it could lose integrity. Other parameters like time and temperature could be relevant.

  • Confirm that the filter moist heat sterilization process did not exceeded the maximum parameters stated by the filter technical document. For example: sterilization temperature, and time. It is common good practice to perform integrity testing when doing sterilization cycle vlaidation of the filter; this way you can have evidence demonstrating that the sterilization paramters (vlaidated) do not impact filter integrity.

Current regulatory expectation (at least enforced en Europe by EMA since Annex 1 to GMP was updated) is the use of PUPSIT for aseptic process control. This is also included in PIC/S annex 1 to GMP, which FDA and many other regulatory egancies are part of.

PUPSIT stands for Pre-Use Post-Sterilization Integrity Testing. This control was put into the guidelines/regulation to itigate this specific risk. It means that you hace to design a process where you could perform an integrity test of your sterilizing filter, afte rsterilization, before its use in the process, to make sure that the sterilization in situ (SIP) of the filter did not impact its integrity.

Of course, you are talking about media filtration (I assume it is for media fill tests), so the risk is much lower, but you get the idea.

I hope my recommendations lead you to the root cause of the failure.

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