Considering Parametric Release
The promising process garners support, with a few challenges ahead.
Daphne Allen, Editor
Industrywide interest in parametric release is growing steadily. Many contractors now have in place, or are busy readying, operations to support the procedure for expediting medical device EtO sterilization. And a number of testing laboratories that help evaluate and validate sterilization methods now offer programs to switch medical device firms from traditional release.
While tradition involves using biological indicators (BIs) to monitor the effectiveness of a process's kill cycle, parametric release involves monitoring key parameters—EtO concentration, relative humidity (RH), temperature, time, and others—to ensure that the process conforms to validated values. As long as it does, firms can release product into distribution immediately.
According to Gregg Mosley of Biotest Laboratories Inc. (Minneapolis), "Virtually any EtO-sterilized product can go to parametric release. It is just a question of whether the product manufacturer is willing to put in the time and effort of switching and whether FDA preapproval is required, for instance with PMA products."
Many leading medical device firms and their contractors have already done so, reports Bill Young, senior director of medical sterilization technology for Sterigenics (Chicago), a member of the IBA Group. Sterigenics has switched many clients to parametric release. Some of these are also using the contractor's expedited EtO process, CycleOne. "With parametric release, you utilize calibrated instruments to document process conformance, not biological organisms," he says. "Since your release is based on measurable data and calibrated equipment, the results tend to be more reliable."
Ethox Corp. (Buffalo, NY) is another contract EtO sterilizer interested in parametric release, preparing what Gary Benson, manager of sterilization and laboratory sales, calls a "breakthrough" to debut by mid-year 2004. But he takes a conservative approach when it comes to recommending it. "Parametric release is an exciting opportunity for EtO users. But it may be for a very specific customer—one with a product that has a history of using EtO and with product design that is well matured and subject to few major changes. But it is not for everyone," he says. "Improving cycle turn times can be achieved through many avenues, and the cost advantages of each should be evaluated."
MAKING THE MOVE
Before switching to parametric re-lease, Mosley recommends first trying a two-day release BI. "A two- or three-day BI helps expedite your process. Typically you do not need to tell FDA about a switch in BIs, as long as the incubation time is validated."
Young says that even if you get a BI down to two days, "it still is two days. You can take even more time out of your process using parametric release and/or an expedited aeration cycle like CycleOne offers," he says.
When preparing for parametric re-lease, Young uses Method B outlined in ISO 11135, with a slight modification. "Method B involves running seven test cycles: one that generates positive BIs, four with predictable fractional growth in the quantal range, and two with total lethality. These results are used to calculate the D-value, which determines the total time to reach lethality. We suggest at this time to utilize the all-kill cycles as the half-cycle dwell time, running an additional half cycle and then doubling the gas dwell time needed for total lethality and using the resulting cycle time for routine production."
Benson advises considering the true value of parametric release. "If you're a high-volume manufacturer producing millions of devices each year and it is critical to control your product stream by a matter of days, if your bioburden is low and in control, and if your products' EtO residual levels are at or below release limits when they exit the EtO chamber, parametric release may make sense. However, the cost of equipment purchase, operation, and maintenance would result in increases in facility overhead and may impact the EtO vendor's ability to control rising costs; that is, price to customer."
Mosley cautions against moving to parametric release if there have been problems with positive results with BIs. "You cannot go to parametric release to circumvent problems because of positive BIs. They point out problems in your process, so you could be getting meaningful results," he says.
If you decide to adopt parametric release, find a contractor that uses spectroscopy or gas chromatography to measure directly the EtO concentration, says Mosley.
Benson agrees that finding the right monitoring equipment is essential. "There are currently few off-the-shelf options to accurately measure the critical parameters—that is, EtO gas concentration—for parametric release," he says. "And there are challenges in means of evaluating relative humidity, for instance. Pressure transducers are much more durable in the harsh EtO environment than the current stationary RH probes are." He adds that Ethox is making strides in this area, and his firm is currently evaluating technology that will make parametric release "more of a possibility and allow for longevity of equipment."
Young says that Sterigenics has been developing monitors over the last eight years and has filed a patent on its design. "It uses microwave spectrometry to measure and monitor the RH and the level of EtO concentration through the unique absorption frequencies of each molecule. The equipment has been in use for a number of years and we believe that the technology is robust and reliable."
There may be some conditions that increase bacteria resistance that parametric release may not be able to identify. One such condition involves the increased number of positive BIs that crop up during especially cold, dry winter months, says Mosley. "The validation may not have been able to consider the low-humidity levels present when producing packaging materials and products during these months. There is too little moisture present, and the low humidity is not overcome by preconditioning. When RH is lower than 40%, the resistance of organisms increases dramatically. RH measurements are not always an accurate measure of the water activity for products and spores. If you use parametric release, you will never know this, because your cycle conditions indicate that you have sterility, when you don't."
Benson says that the upcoming revision of ISO 10993-7 regarding EtO residual levels may complicate parametric release. "A tenfold reduction in the limit of EtO residuals may be proposed, and that will put a strain on manufacturers who are barely complying with the current allowable EtO release limits. They may need to extend their residual hold times as a result."
Nonetheless, cycle time is shrinking, with or without parametric release. Young reports: "Standard EtO might require 18–24 hours of preconditioning, and though we have been able to eliminate this time for many clients, at the very least we have reduced minimum times to an average of 8 hours. We use many factors to expedite aeration and product release." They have made other process improvements, too. "With CycleOne and the Microwave, we have been able to put EtO on a par with E-beam and gamma," Young says.
Benson says that besides parametric release, "there are other means of reducing total cycle time. The general concepts of cycle design used in the industry are the same, but it is the subtle differences that Ethox incorporates to improve cycle performance in regard to microbial inactivation and gas dissipation. You can also optimize your cycles for even greater precision, employ a reduced incubation BI, and step up controls on environmental and bioburden maintenance programs."