Ethylene Oxide Residual Analysis
Ethylene Oxide (EtO or EO) is used to sterilise medical devices. Ethylene oxide gas (usually under pressure) may penetrate container boxes and packaging paunch made of certain material and practically dissolve in medical devices which are generally made of various polymers such as plastic and rubber. The amount of EtO absorbed in the medical device material depends on several factors including the material composition of the medical devices, packaging and shipping material, and sterilization cycles. Once dissolved in the material, EtO gas permeates gradually depending on the solubility and diffusivity of EtO in the material, packaging materials, and aeration conditions. If traces of chlorine or chloride ions are present in the device, they will quickly react with EtO to form ethylene chlorohydrin (ECH). On a slower scale, traces of acid or moisture will convert EtO into ethylene glycol (EG).
EtO and ECH are found to be toxic to humans and exposure to these chemicals are harmful to human health. Since these residues permeate gradually out of the EtO sterilized devices, the patients and to a lesser extent the handler may be exposed when the device is used. The permissible limits of these EtO residues in medical devices will depend on the types of medical devices which have been categorized according to their duration of use on patients. The ISO 10993-7 (2008) on Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals is the guiding document generally accepted for the evaluation of EtO residuals in medical devices. Under this guideline, the allowable limit of each residue, the recommended method of extracting and analyzing the residues, and stringent quality control on the analytical procedure are documented for the evaluation of EtO residuals in medical devices.
Medical Devices Categories and Allowable Limit
(A) Limited exposure – devices whose cumulative single, multiple, or repeated use is up to 24 hours.
(B) Prolong exposure – devices whose cumulative use is likely to exceed 24 hrs but less than 30 days.
(C ) Permanent contact – devices whose cumulative use exceeds 30 days.
SaniChem Resources has developed methods for analysing EtO residuals in various medical devices based on the ISO 10993-7 guideline. These methods have been validated and registered as testing scope under the ISO/IEC 17025 accreditation. There are three in-house methods for the analysis of EtO residues. Method TM-ETO-1 is the main method of determining the level of EtO, ECH, and EG in various medical devices. Basically, this method involves total or exhaustive extraction of the residues from the medical devices and analysing EtO, ECH, and EG by gas chromatography. Method TM-ETO-2 is a validated method for the analysis of EtO in an aqueous solution. Certain manufacturer and sterilization operators have facilities for extracting the residues on-site. It is less cumbersome to ship the extract which requires cold shipment than to ship the medical devices which require dry-ice frozen condition during transit. Method TM-ECHnEG-1 is a validated method for analyzing ECH and EG in aqueous extract.
Dissipation curves Dissipation or decay curves is a tool as recommended in the ISO 10993-7 to estimate the levels of each residue in the medical devices at a certain time after sterilization. This information is useful for the product release date, for example. We provide a package rate for developing dissipation curves for medical devices. A set of samples (normally 10 samples) that are isolated and frozen at various specified intervals after sterilization are analyzed for the residual levels. Normally, the medical devices are isolated and keep frozen at 0, 1, 3, 5, and 7 days after sterilization during the aeration process. At the end of the collection period, the level of EtO residues is determined. Dissipation curves are generated based on the first-order decay rate of the total amount (dose) of the residue in the devices. An example of the EtO dissipation curve is shown below.
Sample submission Sample may be submitted to our laboratory either by hand or through a reliable courier service. We may be able to provide pick-up service with a minimal charge for samples around the Klang Valley. Please inquire about the pick-up rate and availability. For sterilized medical devices, the samples must be placed in a Styrofoam box and filled with dry ice. A well-packed/insulated Styrofoam box may need about 1-2 kilograms of dry ice (pellet) to last 24-hour shipping. ISO 10993-7 guideline stated that there must be some dry ice still present when the shipment arrives at the laboratory to ensure that the samples were frozen during transit. For an aqueous extract of EtO residues, the sample may be placed in 2 mL GC sampler vials. Our experience showed that the solution must be almost full (with about 1-2% head-space), well capped, and insulated. An ice pack may be used to keep the solution cold (but not frozen) during transit. Dry ice must NOT be used as the vial may break when the aqueous solution expands upon freezing. Please use the EtO Test Request Form to record your submission. Sample submission must be accompanied by the test request form and official purchase order. Our policy requires that we cannot provide the test report BEFORE a purchase order from the customer is received. We will provide a written quotation prior to sample submission. Please email or call us for a quotation stating the test required and the number of samples for each test.