Sterilisation ISO 11135 EtO-in-a-Bag (Novel Non-Traditional EtO Sterilization)

[Quarma]

This is about a Novel non-traditional method of ETO sterilisation:

It is called Ethylene Oxide-in-a-Bag (EtO-in-a-Bag, Diffusion method, or Injection method)
This method differs from traditional EtO methods in that Ethylene Oxide-in-a-Bag specifies a volume of EtO instead of a concentration (e.g., 7.2 grains instead of 500-600 mg/L), uses an EtO cartridge or capsule, uses humidichips, or uses a long gas dwell time (e.g., greater than 8 hours).

This method consists of injecting or inserting ETO into a 7 or 35 liter bag which contains the packed products. The ETO diffuses into the product which is in the bag and finally diffuses out of the bag. Temperature is maintained at about 50°Celsius at ambient pressure.

FDA classifies this method as Novel non-traditional
Sterilisers that use that method are marketed by Andersen.

Is there any scientific literature on this ?
Has anybody experience in validating this method ?
Does anybody use this method for sterile medical devices (US or Europe or elsewhere) ?
Would you follow ISO 11135 or ISO 14937 for validating this process ?

There is thread Sterilization Validation ISO 14937 - Sterilizer that uses EO gas diffusion with a similar question but no answer.

Thanks for answering
(Please only answer if you are familiar with this method)

 

[Stijloor]

A Quick Bump!

Can someone help?

Thank you very much!!

Stijloor.

 

[MIREGMGR]

Would you follow ISO 11135 or ISO 14937 for validating this process ?

I don't meet your familiarity/experience requirement, but I can answer the above question from Andersen's published information:

EOGas cycles are validated using the applicable portions of AAMI/ISO 11135.

 

[Doug Tropf]

I'm not real familiar with EO in a bag however, I have heard there are some unresolved questions regarding the legitimacy of the process. At one point there were rumors in the industry of a related TIR in the works but it has never materialized. Attached is a rather dated article on the topic.

 

[Quarma]

Thank you all for answering.
The attached "EO in a bag article" is written by Andersen people, so I would regard it as marketing material, but not necessarily a critical approach.

Also "EOGas cycles are validated using the applicable portions of AAMI/ISO 11135" is a statement by the manufacturer who is naturally biased.
I do by now question if it is valid to simply drop the non-applicable parts, as these do contain critical things like EO-Concentration measurement. (They are non applicable because you cannot assess them - not because they do not apply to the process)

I am still wondering if there are medical device companies out there who got this process accepted with FDA or Notified Bodies or other authorities - and how they did it.

 

[MIREGMGR]

In addition to EO concentration, I'd be concerned in regard to humidity vivification of spore-form microorganisms. A key function of the conventional preconditioning process is overkill-assurance of substantially complete vivification. The bag system's approach to humidity provision so as to achieve complete vivification seems to be both less rigorous and less able to be validated.

 

[MIREGMGR]

It's funny how timing works sometimes in the regulatory world.

This morning, FDA's weekly Warning Letter report includes http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2012/ucm303395.htm issued to Andersen Sterilizers, the company responsible for the bag sterilization process discussed in this thread.

Apparently they haven't made much of an effort to comply with basic FDA requirements for either their company or their products.

I'd guess that, since at least some of their products apparently have been marketed without benefit of 510(k) and the subject matter is sterilization of (typically) surgically invasive and/or blood-communicating devices, a recall will be forthcoming.

 

[MIREGMGR]

Another follow-up: a Warning Letter has been issued to a device maker that uses an EtO sterilization machine based on a bag technique, for a variety of nonconformances. Of particular interest is the FDA's statement that the FDA Recognized Consensus Standard for EtO sterilization, ISO 11135-1:2007, may not be used as the basis for validation of a sterilization process using such a machine. As there is no other generally recognized standard, let alone an FDA Recognized Consensus Standard, for validation of a process based on such a machine, this would seem to be a major barrier to this approach.

Warning Letter FLA-12-41 issued to IsoAid, L.L.C., 16AUG2012

 

[amooney]

FDA do NOT class flexible chamber technology as "novel non-traditional". Validations are done in line with ISO11135 as applicable. The hospital paper from the library on the anderseneurope.com library is probably a good starting place for those considering this technology.

 

[MIREGMGR]

Validations are done in line with ISO11135 as applicable.

How do you reconcile this statement with the above-referenced, below-quoted Warning Letter?

The procedures titled IsoAid – Technical File: Advantage I-125 Brachytherapy Seeds, Sterilization Validation Performance Qualification Protocol, EO-PQ-01, Rev. Orig., (Reference B), references using the elements of standard ISO 11135-1:2007, Sterilization of Health Care Products – (b)(4). However, the ISO 11135-1:2007 standard – Requirements for development, validation and routine control of an (b)(4) sterilization process for medical devices, does not cover sterilization by injecting (b)(4) or mixtures containing (b)(4) directly into individual product packages, or continuous sterilization processes. Therefore, your (b)(4) sterilizer cannot be validated per the ISO 11135-1:2007 standard requirements.

I note from your profile here that you are Managing Director of Andersen Products, which I gather is the same company or perhaps a European affiliate of Andersen Sterilizers, the company referenced three posts up. Has FDA issued a Guidance or some other public document you could point us to, that reverses the position they seemed to describe in the above Warning Letter?