Product Bio-burden Limits and Sublethal Cycle Requirements

Hello Everyone,

I wanted to get some guidance on following issue: -

Our company conducted sub-lethal cycle for 'X' Product in 2013. the sub-lethal cycle was passed.
we have the Bio-burden history for 'X' product which is average 560 cfu/item.
At the time of Sub-lethal cycle the 'X' product bio-burden was 190 cfu/item and on other occasion it's fluctuating and giving more than 190 cfu/item.

1. I want to ask that the Sub-lethal cycle validated, On the basis of External PCDs sterility we can release the product where product Bio-burden are equal or less than 190 cfu/item.

is this Sub-lethal cycle still valid if we have higher bio-burden than 190 cfu/item?

Also How can we determine the Bio-burden limits for this Product.

Thanks in advance,

I guess you are employing an EO sterilization process, and you have validated your process following the overkill approach as outlined in ISO 11135-1?

If yes, you should have more data at hand than a sub-lethal cycle, e.g. you have demonstrated at one point in time that your sterilization process reproducibly delivers an SAL of 10^(-6) in a half cycle, right? So from a lethality point of view, you should be safe, no matter whether you have 560 CFU or less (provided you had no major change in microbial resistance).

Presuming that you have already characterized your bioburden and determined in a risk management process that your encountered levels are safe for the product's indented use, established limits mainly serve the purpose to keep control and catch changes in your manufacturing processes.

Establishing limits: have a look at this paper:
www.mddionline.com/article/establishing-bioburden-alert-and-action-levels

HTH,

Gerhard

planB said:

I guess you are employing an EO sterilization process, and you have validated your process following the overkill approach as outlined in ISO 11135-1?

If yes, you should have more data at hand than a sub-lethal cycle, e.g. you have demonstrated at one point in time that your sterilization process reproducibly delivers an SAL of 10^(-6) in a half cycle, right? So from a lethality point of view, you should be safe, no matter whether you have 560 CFU or less (provided you had no major change in microbial resistance).

Presuming that you have already characterized your bioburden and determined in a risk management process that your encountered levels are safe for the product's indented use, established limits mainly serve the purpose to keep control and catch changes in your manufacturing processes.

Establishing limits: have a look at this paper:


HTH,

Gerhard

Click to expand...

Thanks you for your guidance, i really appreciate your help

[FONT=&quot]Hi there,[/FONT]
[FONT=&quot] In relation to my previous question, for new product, how can I demonstrate that the ETO sterilisation process is effective at the most difficult to sterilize location within the new product packed in the manner in which it is presented for sterilisation?[/FONT]
[FONT=&quot]How can I show that the process challenge device presents an equivalent or greater challenge to the process than the product bio-burden? [/FONT]
[FONT=&quot] [/FONT]
? [FONT=&quot]We have already conducted sub-lethal cycle with worst case product and it was passed, [/FONT]
? [FONT=&quot]We also conduct half cycle validation every two year.[/FONT]
? [FONT=&quot]We conduct Annual review of Cycle Validation every year.[/FONT]
[FONT=&quot] [/FONT]
[FONT=&quot]What else do I need to do to show ETO sterilisation process is effective at the most difficult to sterilisation location?[/FONT]

[FONT=&quot][/FONT]
[FONT=&quot]Thanks for your assistance
[/FONT]

Hi,

from what you wrote you must have already demonstrated in a sub-lethal cycle that your worst-case product's bioburden is no greater challenge to your sterilization cycle than any other product of your product family.

What remains for your new product is to show that your original worst-case product remains indeed worst-case. Consult AAMI TIR28:2009/(R)2013
"Product adoption and process equivalency for ethylene oxide sterilization", and especially the annex containing questions that can be used as a checklist, for detailed guidance on how to evaluate your new product.

Generally, you define your most difficult location based on a scientific rationale which location the sterilant gas has to pass the most tortuous pathway to get to.

Apart from the effectiveness of your sterilization process, do not forget to think about your residuals ...

HTH,

Gerhard