Frequency and sample size for lot release of EtO sterilized products

[shimonv]

Hi everyone,
I would like to do some benchmarking with you:
I was given to understand that EtO residuals and biological indicators are tested for each lot and bio-burden and LAL are done periodically (quarterly or after a certain number of manufactured LOTs).

What is your experience with that and what sample size to you use (I suspect there is no explicit guidance on that)?

Thanks,
Shimon

 

[Cthames]

Hello Shimon,

From my experience (this was for one company, not sure how others do it), ETO residuals are validated and not measured every lot. This validation usually is the final piece of a sterilization validation and is repeated when new risks are introduced or every 1-2 years. Granted, the company I was working for had 600 SKUs which fit into 4 finished product families. We didn't specifically validation individual SKUs, so I'm not sure what the standard practice is for that.

We used 34 biological indicators with each sterilization run of 14 pallets of medical devices. We placed these inside worst cases devices (within pouches) and had the sterilizer place them in strategic locations within the sterilization chamber. The consultant (who worked closely with the sterilizer) came up with this sample size. I don't have access to that validation anymore, but I believe it was based off a combination of how many biological indicators we tested during our validation runs, and how many strategic locations we had to account for (gas entry points, gas exit points, center of room, hardest to reach locations, etc).

There may be guidance in ISO11135:2014, but I cannot remember.

 

[chris1price]

Hi, as Cthames said, you validate the residuals, so there is no requirement for monitoring each lot. However, I am aware that some companies do perform this on every lot.

I do not think there is any standard for LAL frequency, I have seen it done for every lot, once per month and once per quarter. I suspect this is very dependent on the risk posed by the product and the manufacturing processes.

Bioburden is again validated, so monthly should be sufficient, there is nothing in the standard but 10 samples per quarter would match the frequency used for gamma sterilization. ISO11737-1 A.8.1 says "It is common practice to use a sample size of between three to ten items for routine monitoring of bioburden levels."

ISO11135, table C.3 lists the number of BIs to use. for routine monitoring of N cubic meters of load space over 10m3, it is (30+(N-10))/2