Be in the Know about EtO

Originally Published MPMN May 2009

PRODUCT UPDATE

Be in the Know about EtO

Expedited processing and better controls amp up the efficiency of ethylene oxide sterilization while revised standards affect validation

Shana Leonard

One of the most effective killers out there is actually responsible for our health and safety. Employed for its proven lethality of microorganisms, ethylene oxide (EtO) is among the most commonly used medical device sterilization methods owing to its compatibility with a variety of materials, which ensures the delivery of safe and sterile products. The gas is frequently used for the sterilization of disposable medical products, and is relied upon for processing many devices and materials that cannot withstand sterilization by other means due to sensitivity to such factors as heat, irradiation, or discoloration. Because Et0 is the sterilization method of choice for so many applications, contract sterilizers are laboring to improve processing speeds and controls while catering to the changing needs of industry standards.

EtO on the Go
A traditional EtO processing cycle consists of three steps: preconditioning, sterilization, and aeration. Prior to sterilization, biological indicators (BIs) are placed in the product load, which is then transported to an environmental preconditioning chamber for heating and moisturizing according to preset parameters. Next, the product load is moved to the sterilization chamber for the actual EtO processing. After sterilization, product is placed in an aeration cell to allow for gas dissipation. The catch, however, is that this seemingly simple three-step process can take, from start to finish, anywhere from one to two weeks.
Because of the always-pressing demand to decrease time to market, several contract sterilization companies provide expedited EtO sterilization programs exclusively for quick turnarounds. Sterilizers are able to significantly reduce cycle times for these specialty programs by employing parametric product release, which removes the use of BIs from the overall process. Although parametric release is often used in other sterilization techniques, it is not often used in conventional EtO processing because many sterilizers prefer to use BIs to ensure control over the four variable EtO parameters: gas concentration, temperature, relative humidity (RH), and time of exposure.
Instead of referring to BIs to check sterility, parametric release relies on the establishment of specifications for each of the four parameters and then in-process monitoring to ensure that the preset conditions are being met. In addition to ensuring sterility based on verifiable data and expediting the entire process, parametric release also eliminates the potential for false-positive results and cuts costs associated with BI use.
Steris Isomedix Services (Mentor, OH; www.isomedix.com) is one such company that, in addition to its conventional EtO processing, offers medical device OEMs an expedited processing capability. "EOExpress is a Steris technology that combines all-in-one processing and parametric release to provide sterilization and release of product to market in one day," explains sales director Thad Wroblewski.
With this program, products still undergo the same three phases of the cycle, just at an accelerated rate and in only one vessel. During dynamic environmental conditioning, the product load is conditioned at the same temperature as sterilization. This accelerated conditioning features a more-rapid increase in temperature and RH than in conventional cycles, which, in turn, enables better homogeneity of temperature and RH, according to Wroblewski. Furthermore, expedited conditioning reduces the amount of time that the product is exposed to high temperature and RH.
The sterilization phase of the EOExpress method increases lethality to microorganisms while reducing the concentration of EtO and, consequently, the residuals. Accelerated aeration is performed under vacuum using proprietary processes at a higher temperature than with conventional EtO processing. It also enables faster and more-uniform removal of EtO residuals, Wroblewski says.
Likewise, Sterigenics (Oak Brook, IL; www.sterigenics.com) is also equipped for accelerated EtO sterilization through its CyclEOne process. Used in conjunction with parametric release, the CyclEOne process provides single-chamber sterilization in just 12 to 24 hours. And, for OEMs in a serious time crunch, Sterigenics has taken a cue from the theme park industry by offering a front-of-line pass of sorts. Purchasing the EOStat option bumps a company's product to the top of Sterigenics' EtO to-do list.
It's the Heat and the Humidity
Adding to Sterigenics' already-efficient operations is the use of a microwave spectrometer, which allows for the quantifiable introduction of RH in the sterilization chamber, according to the company. Designed to self-calibrate prior to each cycle, the microwave spectrometer calibrates only to the EtO molecule, even if other gases are present in the chamber, the company states. In addition to monitoring the levels of EtO gas in the chamber, the instrument calculates the amount of RH present in the vessel using patented hardware.
Ethox International Inc., STS Life Sciences Div. (Rush, NY; www.ethoxsts.com)goes a step beyond RH calculations to guarantee humidity control in its conventional EtO processing methods. "We do direct humidity readings with our sterilizers," says Jason Voisinet, the company's program manager of laboratory sterilization services. "That gives you the actual humidity range that's in the vessel rather than a theoretical value. Typically, when you calculate [RH], you can overhumidify." He adds that, to the company's knowledge, performing direct humidity readings is a unique capability offered by Ethox.
Direct measurement, Voisinet says, especially lends itself to sterilizing products that are sensitive to temperature or humidity. Falling into this category are many combination products, which often require specialty low-humidity or low-temperature EtO sterilization cycles to accommodate their unique composition. "Generally, you try to run EtO cycles at optimal humidity and temperature," Voisinet says. "For instance, 49° to 54°C and 60% RH are ideal for lethality of microorganisms using EtO. Once you start lowering those parameters, it is more difficult to kill those microorganisms. So, other parameters are then optimized."
Changing What's Acceptable
In the case of EtO, what goes in must come out. Although medical devices are exposed to EtO in order to kill bacteria and microorganisms, part of the sterilization process is aeration. The objective of this phase is to help expedite outgassing of EtO from the product because, after all, the chemical is toxic. To further ensure that the lingering amounts of EtO and its by-products--ethylene chlorohydrin (ECH)--that get trapped in a product's pores or materials do not surpass acceptable maximum limits, residuals testing is a necessary part of EtO sterilization validation.
Significant changes are afoot in EtO residuals testing, however. In January, ANSI/AAMI/ISO 10993-7, Biological evaluation of medical devices--Part 7: Ethylene oxide sterilization residuals, was revised to include lower acceptable limits for residual EtO and ECH in individual EtO-sterilized medical devices. The acceptable level of EtO for products in the limited exposure category was dramatically lowered from 20 to 4 mg per device while ECH was reduced from 12 to 9 mg. Prolonged and permanent limits for the maximum allowable residuals remain unchanged.

"Probably anything that's going to be sterilized by EtO is going to be affected by this," observes David Simmons, study director at Nelson Laboratories Inc. (Salt Lake City; www.nelsonlabs.com), a company specializing in sterilization and laboratory testing, including residuals testing. "Products that are bulkier, like hospital gowns and drapes, which hinder aeration but are quick to release EtO, are going to be more susceptible to this lower limit than hard plastic products for which it takes time for the EtO to get in and then come out again."

Nelson Laboratories is actively working to get the word out to medical device OEMs about the updated standard, even putting a prominent alert on its Web site. The company is prepared to work with device manufacturers whose current validations do not adhere to the updated limitations and assist them in meeting the new requirements.
"A lot of [OEMs] need to go back and look at their sterilization validations," Simmons says. "In some cases, it may mean that they actually have to change the way they're doing sterilization. They may need to change sterilization parameters in order to still meet the limits. It's probably more time associated with quarantine before the product can be released, but in some cases it could have a greater impact."
Copyright ©2009 Medical Product Manufacturing News