EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2008

medwise

Involved In Discussions
#1
Dear all,

We manufacture suction irrigator (7.5m tubing set with probe). Contact period is less than 24h with the patient and end user (surgeon).

The EO used during sterilization is 35kg. The aeration time is 20days to reach a residual level of 20mg. But according to the 2008 version we are required to not exceed 4mg in 24hours. To met this requirement our aeration time would be close to 5weeks.

Can anyone suggest what can be done to achieve the 4mg within a week of aeration?

Your help will be much appreciated.:)

Regards
Romit
 
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M

MIREGMGR

#2
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

Is your aeration already proceeding at the highest temperature your sterilization and plastics people can agree on?

Do you have the option of changing resins, so as to decrease absorption?
 

medwise

Involved In Discussions
#3
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

Hi MIREGMGR,

The aeration is done in our normal warehouse condition i.e. 25 degrees.

Do you recommend to have a system in place in our facility which can help in aeration? Is this the normal practice in the industry?

Regards
Romit
 
M

MIREGMGR

#4
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

Are you saying your aeration is done in open conditions, in normally occupied areas? How do you control for personnel safety and potential explosive gas levels with fresh product loads? How do you validate your aeration if you don't know the worst-case environmental conditions?

Our sterilization contractor does all aeration in a limited-access aeration room with explosion-proof electrical systems, controlled ventilation rates to manage maximum gas concentrations, makeup heat to increase the aeration rate, and periodic gas detection and alarms as a safety backup. I believe most of the safety elements are required per applicable AAMI sterilization system standards/TIRs. Entry to the aeration room is limited to certain of their personnel, and requires a gas mask. I believe all of the exhaust air from the room goes through a scrubber to prevent EtO venting to the atmosphere.

I'm not sure, but I think there's relatively little makeup/exhaust air because the recirculation goes through a scrubber as well, integrated with the heating capability. So, the gas concentrations (and therefore partial pressures) are kept low in the room, which also helps with aeration rate.
 

medwise

Involved In Discussions
#5
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

Once the sterilisation is done the load is aerated for 12hrs at contract sterilizer's facility. Then once we receive the load we keep them in our warehouse (closed) for EO to aerate for 0 days from the tubing set to reach 20mg. But according to the new standard we have to reach 4mg. What can be done to achieve 4mg in less number of days.
 
M

MIREGMGR

#6
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

I apologize for glossing over the tubing set description above. Tubing sets are tough because of their form factor and because you usually don't have the option of changing materials. Increased temperature may be of limited utility because the problem is slow gas exchange through the tubing lumens.

The only other angle would be to conduct your extended aeration in a vacuum-capable chamber, pulling and then releasing vacuum cycles. Repeated vacuum cycles will greatly increase the rate of gas exchange within the tubing lumens.

A decommissioned EtO sterilization chamber would be ideal for that, because it's designed for pallet loading and vacuum cycling. A vacuum-capable autoclave tank without the pressurization and circulation systems might work as well. In either case, a gas removal/scrubbing system and other safety systems would need to be engineered and added, and appropriate safety procedures and training put in place.
 
D

drewsky1

#7
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

We are in the process of meeting the requirements of 10993-7 which reduces the allowable EO residual limits from 20mg to 4mg. I am concerned about the impact on the change in process and if we need to do additional functional testing for the first lots that are manufactured. Can this change have an impact on functionality of devices?
 

medwise

Involved In Discussions
#8
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

I have been informed by a laboratory in Sydney that there are quite a few organisation who release the product based on "discounting factors". Apparently, a calculation can be made depending upon the intended use and period of contact. I tried to find something like this in the standard ISO 10993-7:2008 but came across nothing. Upon my query to the Laboratory Manager, I was explained that the amount of EO residual present after 24 hour areation could be divided by the maximum number of device use. For example if the EO residual after 24 hrs exhaustive study is 50mg/device and the intended period of use is 3 hours then 50 divided by 3. Her rationale behind this is that 50mg of EO wont be tranferred into the patient because the dissipation time or retention period of EO varies due to size (Gas Chromatography). Is this rationale enough to satify a regulatory body? I am not convinced however your advise would be much appreciated.

Also, do we have to validate the test method individually on our specific products or the validation of the test method which has been done by the lab internally is sufficient?

Thanks
Romit
 

medwise

Involved In Discussions
#9
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

:)
I apologize for glossing over the tubing set description above. Tubing sets are tough because of their form factor and because you usually don't have the option of changing materials. Increased temperature may be of limited utility because the problem is slow gas exchange through the tubing lumens.

The only other angle would be to conduct your extended aeration in a vacuum-capable chamber, pulling and then releasing vacuum cycles. Repeated vacuum cycles will greatly increase the rate of gas exchange within the tubing lumens.

A decommissioned EtO sterilization chamber would be ideal for that, because it's designed for pallet loading and vacuum cycling. A vacuum-capable autoclave tank without the pressurization and circulation systems might work as well. In either case, a gas removal/scrubbing system and other safety systems would need to be engineered and added, and appropriate safety procedures and training put in place.
I have been informed by a laboratory in Sydney that there are quite a few organisation who release the product based on "discounting factors". Apparently, a calculation can be made depending upon the intended use and period of contact. I tried to find something like this in the standard ISO 10993-7:2008 but came across nothing. Upon my query to the Laboratory Manager, I was explained that the amount of EO residual present after 24 hour areation could be divided by the maximum number of device use. For example if the EO residual after 24 hrs exhaustive study is 50mg/device and the intended period of use is 3 hours then 50 divided by 3. Her rationale behind this is that 50mg of EO wont be tranferred into the patient because the dissipation time or retention period of EO varies due to size (Gas Chromatography). Is this rationale enough to satify a regulatory body? I am not convinced however your advise would be much appreciated.

Also, do we have to validate the test method individually on our specific products or the validation of the test method which has been done by the lab internally is sufficient?

Thanks
Romit
 
M

MIREGMGR

#10
Re: EO (Ethylene Oxide) and ECH (Ethylene Chlorohydrin) Residual as per ISO 10993-7:2

I have been informed by a laboratory in Sydney that there are quite a few organisation who release the product based on "discounting factors". Apparently, a calculation can be made depending upon the intended use and period of contact. I tried to find something like this in the standard ISO 10993-7:2008 but came across nothing. Upon my query to the Laboratory Manager, I was explained that the amount of EO residual present after 24 hour areation could be divided by the maximum number of device use. For example if the EO residual after 24 hrs exhaustive study is 50mg/device and the intended period of use is 3 hours then 50 divided by 3. Her rationale behind this is that 50mg of EO wont be tranferred into the patient because the dissipation time or retention period of EO varies due to size (Gas Chromatography).
I'm not familiar with this terminology or approach. Per Figure C, my understanding is that except for Special Situations, Categories and Devices, a device must meet the requirement for total residual content for its use-period category (as opposed to its actual use period, but based on an extraction for its use period); and for surface contact and implantable devices, the TCL limit for its amount of contact area.

Perhaps there's a published guidance that I'm not familiar with, though. What does your lab say is the source-document and section for its explanation?

4.4.6.2 says that simulated use extraction, i.e. for the actual period of use, is the reference method. 4.4.6.3.1 says that exhaustive extraction is an acceptable alternative; however, the standard specifically states that "...because such an extraction precludes measurement of dose as a function of time, it does not ensure that the mass of residue is not delivered to the patient on the first day (...) of exposure."

It sounds to me as if the lab is doing an exhaustive extraction, then factoring it by use-exposure time as a fraction of the 24 hour Limited period, with an implied justification that the mass of residue will be delivered on a time-linear basis. That technique seems to me to be directly in conflict with the quoted statement above, which I read to state that it is impermissible to assume delivery on a time-linear basis. In particular, if a simulated use extraction for three hours (in your example) would yield a higher extracted value than the lab's method, then my judgement would be that the lab's method is non-conforming.​

Also, do we have to validate the test method individually on our specific products or the validation of the test method which has been done by the lab internally is sufficient?

My interpretation is that the lab's test method validation is sufficient, but that it should have been done with test devices that are morphologically and chemically similar to, and defensibly as challenging as, your production devices. I would think they would have been aware of that expectation, and would have developed their processes using a worst-case-challenge-device approach, which they could document for you. 4.4.6.1 may apply.​
 
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