Ethylene Oxide Sterilization Validation-Reference Load

[erj526]

Hello! My company is about to run an EtO sterilization validation on medical devices. We were told that our reference load, or dunnage load, needed to be filled with all products that represent the worst case load and that these products will be scrap. For a small company like us, this is just not possible to have that many products (800 something products) going to waste.

Does anyone know if the reference load needs to actually consist of the same product? Can it just be boxes of the same filled with something else like packing peanuts or something? Is there any possible way around this?

Any help with this is greatly appreciated!

 

[Rincewind]

Hello,

you should perform a documented worst case evaluation of your products and run the validation with those worst case products. Only by doing this you can claim that the chosen sterilization method is able to provide a sterile product.

You don't necessarily have to this with all 800 products of yours, only with the ones you deemed to be the most difficult to sterilize (the worst case products).

 

[Ed Panek]

What Rince said. Give them samples of your highest burden products to make a worst case example. There is a lot of upfront cost in this but once established you can paper adopt new products. Try to have the validation cover a "family" of products where you can (Similar products grouped together)

 

[vaderlander]

Hello everybody
I need your help as professionals in the sterilization validation


we performed temperature/relative humidity distribution study within the reference load (data loggers were placed inside of the boxes over pallets)

there is the acceptance criteria that the temperature in the chamber during exposure phase shall be 40 - 50 degrees

does it mean that the same temperature have to be inside the boxes with products?
if not - what difference is allowed?

 

[planB]

there is the acceptance criteria that the temperature in the chamber during exposure phase shall be 40 - 50 degrees
does it mean that the same temperature have to be inside the boxes with products?

Applicable standard ISO 11135:2014 does not prescribe specific numerical values but generally requires - quote from section 9.4.3.1:

a) that the specified acceptance criteria are met throughout the load for the duration of the proposed routine process specification, and
b) reproducibility of the process.

and in the related guidance D.9.4.3.3:

During PQ, it is important to take into account the relationship between the load temperature and the chamber temperature in order to ensure adequate load temperature in the routine process.

So would your measurements meet your specified acceptance criteria? If yes - and if you are also meeting the specified requirements for sterility and other requirements (e.g. residual levels and continued device functionality after sterilization), you should be all settled.

HTH,

 

[vaderlander]

Applicable standard ISO 11135:2014 does not prescribe specific numerical values but generally requires - quote from section 9.4.3.1:


and in the related guidance D.9.4.3.3:


So would your measurements meet your specified acceptance criteria? If yes - and if you are also meeting the specified requirements for sterility and other requirements (e.g. residual levels and continued device functionality after sterilization), you should be all settled.

HTH,

PlanB, thank you
I have read this clauses of ISO11135

As I mentioned, we have preestablished temperature/RH range at the each stage: preconditionning, sterilization (exposure) and aeration but these limits are for outside of load

My issue is: should be the temperature inside sterile barrier system the same as outside of the package during the exposure phase?

Is the difference in 1-2 degrees is significant if the sterility is achieved? (as you mentioned "During PQ, it is important to take into account the relationship between the load temperature and the chamber temperature in order to ensure adequate load temperature in the routine process. "

how to justify it?

 

[planB]

As I mentioned, we have preestablished temperature/RH range at the each stage: preconditionning, sterilization (exposure) and aeration but these limits are for outside of load

Have a look into ISO 11135:214, section 9.5.4: in this list you will find requirements to also physically characterize / specify your load.

My issue is: should be the temperature inside sterile barrier system the same as outside of the package during the exposure phase?

Not necessarily. This really depends on how you have set up your cycle. The important point is though, that within the specified _load_ temperature range your sterilization cycle reproducibly meets all defined acceptance criteria.

Is the difference in 1-2 degrees significant if sterility is achieved?

In case you meet your microbiological and physical acceptance criteria, then this difference may be OK.

HTH,

 

[vaderlander]

[QUOTE="planB,
Not necessarily. This really depends on how you have set up your cycle. The important point is though, that within the specified _load_ temperature range your sterilization cycle reproducibly meets all defined acceptance criteria.
HTH,[/QUOTE]

PlanB, thank you a lot.
I got the approach that you described referring to the standard.

then the issue is to set up a correct acceptance criteria.

To be more specific
During the validation it was set that the temperature range in the sterilization chamber should be 40 - 50 degrees

When we perform requalification we place data-loggers inside the boxes within the load and see that part of values are within and comparable with the chamber temperature range
part of results are to close to the lower limit (40 degrees)
a value of an individual data-logger can be 32-33 degrees.

does it mean if we have achieved SAL -10^6, accepted EO?ECH residuals and functionality then may we say that the minimal load temperature of 32 degrees is acceptable for the aim of sterilization?

 

[planB]

It seems to me that you have not specified your load temperature according to ISO 11135:2014, section 9.5.4.f.5, which is another parameter, independent from the chamber temperature (refer to ISO 11135:2014, section 9.5.4.f.3) during you initial validation. You might want to add this parameter to your process specification.

Have you performed mapped (i.e. with data loggers) half and full cycles, reproducibly demonstrating the required lethality at a reproducible temperature range then 32 - 33 °C may be acceptable (though this would be a very narrow range in a specification, that might be hard to meet in all runs)

Validation of residuals is a separate activity - have a look into ISO 10993-7; continued functionality can be evaluated, but you might want to consider more potentially significant parameters other than the load dwell temperature in your assessment.

HTH,