Process Refinements and Improved Tools Ease Materials Selection

Gamma radiation allows product to be shipped immediately after sterilization. Photo of a Cobalt-60 source courtesy Steris Isomedix Services.

The materials available to package medical devices, and the methods used to sterilize them, haven’t changed radically in recent years. But that doesn’t mean things are standing still. Sterilization service and equipment providers continue to refine their processes, and new tools are providing better information on materials compatibility, making it easier to match material and method.

PROCESS REFINEMENTS: EtO

EtO has evolved to the point that most packaging-related challenges can now be overcome, says David Parente, senior consultant and manager at NAMSA Advisory Services (Northwood, OH). “Those processes have become so efficient that they can often adapt the process to overcome the hurdles that exist,” he explains. Drawing a deep vacuum and supplying humidity, for instance, can help force gas into a package and sterilize every area of a medical device with many deep crevices.

With the help of sophisticated software controls and other new developments, Sterigenics International Inc. (Oak Brook, IL) has helped customers streamline outgassing. The firm has been successful in cutting time from about 10–30 days to less than 24 hours out the door, claims Bill Young, vice president of technical services. A move from 13- to 30-pallet sterilization chambers has also trimmed turnaround time. “There has been a migration to much larger sterilization chambers,” Young says.

In some cases, use of parametric release can also shave off time by eliminating the need to test biologic indicators. But even biologic indicator processes offer options. “Typically, if you have a product that has to sit for residuals, you could evaluate a reduced-incubation period with your biological indicators,” says Young, adding that this could bring some processes down from seven to as little as two days.

Another way EtO sterilizers are shortening turnaround time is to move to an all-in-one process, with preconditioning, sterilization, and aeration taking place in the same chamber. But International Sterilization Laboratory (ISL; Groveland, FL) has found that the climate at its Florida location eliminates the need for preconditioning, shaving off as much as 24 to 36 hours, says general manager Wes Mathis. Process improvements in the method, says Mathis, were driven by the emergence of gamma sterilization, which has a big turnaround-time advantage. At that time, EtO was generally a four-day process. “My average turnaround time today is about a day and a half,” says Mathis, “so we’re on the same basic playing field that they are.”

Gamma totes move on a conveyor in Steris Isomedix Services’ Ontario, CA, facility.

PROCESS REFINEMENTS: RADIATION

One of the major challenges associated with E-beam sterilization has been its penetration ability, but equipment technology has largely overcome limitations in that area. “We now have increasingly bigger and more-sophisticated machines that can deliver doses that can penetrate much more than they could 10 years ago,” says Young. The company is also exploring x-ray sterilization, which Young calls “something that we see as a prominent fixture on the horizon.” It is a thorough method, with material impact equal to or less than gamma. It also penetrates well, he says, predicting that x-ray will likely become a significant method in the next two to three years.

Carton configuration can also have a big impact on radiation sterilization, reports Betty Howard, Gamma TechTeam manager at Steris Isomedix Services (Mentor, OH). Smaller, narrower groupings are easier to penetrate, she says. Failing to heed this advice could require additional sterilization cycles. Even product orientation matters, and products with a dense side and a light side should be alternated in the box for even penetration. “Little things like that sometimes can make a huge difference,” Howard says.

Because uniform product arrangement within the package can increase throughput with E-beam sterilization processes and help meet tighter dose-exposure limits, thermoformed packaging has become an important factor in that realm. “The lower cost of thermoformed packaging offers significant opportunities to improve sterilization efficiency by presenting the product in the most favorable orientation to the electron beam,” says Tom Stephan, vice president, business development, BeamOne LLC (San Diego).

VHP IN THE HOUSE

A newer option for device manufacturers is vaporized hydrogen peroxide (VHP), also known as gas plasma. Advanced Sterilization Products (Irvine, CA), a division of Johnson & Johnson—which pioneered the technology in 1993—has been working to build awareness of VHP as an in-house option, says director of scientific and industrial business Mike Valentine.

Valentine estimates that approximately 60% of medical device companies currently outsource sterilization, primarily because they don’t want the hazards of an EtO process in-house, or because they don’t want to take on the expense of in-house radiation sterilization. But the company’s Sterrad gas-plasma equipment doesn’t present these problems or compatibility issues that radiation does, Valentine says. “When companies come to us, they usually have a material issue, or they want more control of their supply chain,” says Valentine.

Having sterilization in-house means products can be sterilized in primary packaging, without the need to pack into shippers for an off-site trip. “Where Sterrad belongs in your facility is in the packaging area, right off the packaging line,” Valentine says. “That’s where our value proposition is to customers.”

Eagle Medical Inc. (Paso Robles, CA), a provider of contract assembly and packaging services, also saw the value proposition in having sterilization available on-site. It added VHP to its capabilities in September, reports regulatory/quality assurance manager Jody Birks. The company decided to offer VHP when it found out that there were no contract service providers offering this type of sterilization. “I thought, wow, there’s a niche there,” Birks says. It will also provide many customers an opportunity to change over from EtO sterilization, for which Eagle sends out to a contractor.

One customer is using Eagle Medical’s VHP process for a kit-type product that includes an orthopedic pin in a vial. To adapt the package for VHP, which requires permeable packaging, the customer had its supplier punch holes in the vials so that the gas could enter. The switch to VHP shaved five hours off sterilization itself and reduced turnaround time by as much as two-thirds. This is increasingly important for customers, “especially since the industry seems to be moving toward just-in-time [processing],” Birks says.

Product is loaded into an EtO vessel in Steris Isomedix Services’ San Diego, CA, facility.

NEW INFORMATIONAL TOOLS

Sterilization is also being streamlined from another angle: new tools and information to help packagers select compatible materials.

In addition to updating its technical information report (TIR No. 22) to the newly revised and split ISO 11607-01 and 11607-02 in 2006, AAMI is updating its guidelines to include all currently used sterilization methods, says Karl Hemmerich, plant manager and technical adviser at Steris. Hemmerich is updating the existing radiation section, published in 1997, to include metals, gas, and more detail on elastomers, among other things. Thus, the ISO standards and the AAMI guidelines will work together to present a complete picture for packagers. “With that foundation, and also this enhanced materials information, you have a place to go,” says Hemmerich. “The information is getting better and better, so that the selection from the get-go is getting better.”

The process began in June and should be completed in mid-to-late 2007. The radiation section will include a graph with dosage on one axis and materials on the other, using a green-yellow-red coding scale to help engineers determine whether a material is safe at a particular dose, whether further testing is needed, or whether the material is not safe. “It will be an easier way of visually selecting material candidates,” says Hemmerich.

ROOM FOR IMPROVEMENT

Though we haven’t seen many packaging material breakthroughs in recent years, there is certainly room for improvement, says Steven Richter, president and CEO, MicroTest Laboratories Inc. (Agawam, MA).

The challenge with combination products, such as drug-coated devices, is that portions of the product cannot be exposed to certain forms of sterilization. “As we move forward with combination products, this is going to become a real problem,” Richter says. Packaging will likely be developed to shield certain areas of a product from radiation, such as portions that require a metered dose of radiation rather than a bolus, according to Richter. “There should be some emphasis on that in the future,” he says. At this point, “there really aren’t a lot of options for a device maker to choose from.”

There has been some work done to develop paper-based (or cellulose-based) materials as an alternative to Tyvek, says Amy Karren, microbiology section leader at Nelson Laboratories Inc. (Salt Lake City). However, these present problems for VHP and sterilization methods involving humidity.

Karren also knows of a company developing a new polystyrene material that, rather than seeking to avoid the cross-linking associated with E-beam sterilization, actually embraces it. The rigid material is currently being looked at for devices, rather than packaging, though it could have potential for rigid trays. Instead of changing to an unpleasant brown color during exposure, the material turns blue. “It was an iridescent blue,” Karren says. “It was gorgeous.”

No matter how many new materials or methods are developed, however, those being used today aren’t likely going anywhere. Each method has its drawbacks, and each works very well for some types of products. Industry experts say there will always be a need for such tried-and-true methods as steam and dry heat. “If your product can handle a dry-heat sterilization cycle,” says Karren, “it’s a great method.”