Ethylene Oxide Sterilization Validation question

Sam Lazzara

Trusted Information Resource
#1
In reviewing a contract manufacturer's EO sterilization process I see no evidence that a "bioburden resistance" study was performed to demonstrate that the resistance of the natural bioburden is equal to or less than the resistance of the biological indicator as per ISO 11135-1:2007 8.6.b and B.1.4.

This is typically achieved by performing short, sublethal cycles comparing natural product sterility to BI sterility, and there should be more growth among the BIs than the actual products. It can also be achieved by identifying the type and amount of natural bioburden on the product and doing a literature review to (hopefully) show that the natural bioburden organisms are less resistant than the indicator organism (B. atrophaeus).

The contractor's rationale is that the product bioburden is less than 1000 CFU. However, there is no evidence that the bioburden organisms have ever been identified so their resistance can be compared to B. atrophaeus. Nor have they done any sublethal studies as mentioned above.

I am pretty sure the rationale of having bioburden less than 1000 CFU is from a now superseded standard.

Any ideas about this?
 
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Sam Lazzara

Trusted Information Resource
#5
Note to self: "Save superseded standards".

I confirmed that the requirement to address bioburden resistance was first added to ISO 11135-1 in the 2007 (current) version.
 
C

cfeezor

#6
I know this discussion has been dead for over a year, but a related questions/topic recently surfaced as I was reviewing an previous EO sterilization validation and drafting a new one.

First, I have to say that I do not claim to be a sterilization expert, but I have been involved and led sterilization validation activities on a number of projects, but have always left the nitty-gritty details to others.

There seems to be a general understanding that a natural bioburden less than 100 CFU/device is sufficient to say that the natural bioburden is less resistant to the biological indicator; however, I can not find this definitive threshold in 11135 or any of the related standards. Am I missing something? In reports, I have seen the rationale for this threshold based on the fact that a majority of natural bioburden is aerobic and that the natural bioburden is generally considered less resistant to EO sterilization compared to the bacillus atrophaeus used as the BI. I can generally accept this rationale; however, I have not been able to find any evidence to support these statements.

Can anyone suggestion where to find evidence to support the 100 CFU threshold or a means to support the rationale for the threshold?

I know that my alternative is to run "real" product alongside my PCDs in a fractional cycle and run a test of sterility on those devices; but for the sake of being efficient I want to minimize testing if the rationale is solid.

Thanks,Chris
 
M

MIREGMGR

#7
There seems to be a general understanding that a natural bioburden less than 100 CFU/device is sufficient to say that the natural bioburden is less resistant to the biological indicator
Never heard of it.

And how would you prove that the measured bioburden is "natural", and what the biological characterization of that bioburden is? If your manufacturing uses synthetic materials that have been shipped and processed in man-created, technically managed environments, defining "natural" in my view is hopeless.

Can anyone suggestion where to find evidence (...for such a...) threshold?
Not me, and I sure wouldn't go there.
 
#8
Hi,

I am aware that this thread is inactive, however, my intention is to share my doubts on the same issue. Recently I came across the same thing, by reviewing sterilization validation protocol & report from our subcontractor. They validated the process with three half cycles and one full cycle. Therefore, no fractional/short-time cycle performed.
I was digging into ISO 11135:2014 as I usually do, but found no concrete guidance on this.
Would it be the right thing to approve this without the fractional cycle? I am a bit skeptical.
Thanks in advance!
 
L

locutus

#9
Emina I would be skeptical if fractional or challenge cycles were not done, especially if using a PCD or another BI method for routine sterilisation. The purpose of the fractional cycles is to hopefully establish your D-value showing some killed, some live, so that can get that sterility assurance level to the 10-6. My read of ISO 11135 is that one (1) fractional cycle is performed for establishing BI recovery between the PCD and natural product. Personally, I would not accept without a fractional cycle and have not done so in the past.
 
#10
Emina I would be skeptical if fractional or challenge cycles were not done, especially if using a PCD or another BI method for routine sterilisation. The purpose of the fractional cycles is to hopefully establish your D-value showing some killed, some live, so that can get that sterility assurance level to the 10-6. My read of ISO 11135 is that one (1) fractional cycle is performed for establishing BI recovery between the PCD and natural product. Personally, I would not accept without a fractional cycle and have not done so in the past.
Thank you. Exactly what I was thinking. :)
However, they informed me afterwards that this actually was a revalidation. Even though it wasn't stated anywhere. :agree:
 
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