Considering sterilization during product and package design may save you money, time, and trouble.
by Christina Elston
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Packaging must be able to withstand the pressure changes typical with EtO processing. Photo courtesy Sterigenics. |
In the old days, there was steam, perfect for sterilizing glass syringes, metal instrument trays, and other older-technology medical products. But put many current products in an autoclave, and they’re likely to melt—right along with their packages. Today in the United States, approximately 95% of healthcare devices sterilized in an industrial setting use either ethylene oxide (EtO) or radiation sterilization methods, reports Clark Houghtling, corporate account manager and senior EtO technical specialist at Steris Isomedix Services (Mentor, OH).
But though these sterilization methods are unlikely to melt a package outright, they may still stress packaging in various ways. Niki Fidopiastis, director, sterilization consulting services, with the SteriPro division of Sterigenics International (Oak Brook, IL), states that among the primary factors to be considered when selecting packaging materials are “the resilience of the packaging material during the intended sterilization process and facilitating that sterilization process with the selected materials.”
ETO
With one of the most popular methods, EtO sterilization, the biggest stress is on package seals. “Since industrial EtO sterilization is most often performed at subatmospheric pressures and involves numerous pressure changes, packaging must be able to withstand both the vacuum levels and the rate of changes in pressure that occur during the process,” says Houghtling.
In addition, users must consider the effects that pressure as well as heat and moisture have on the package. “EtO processing induces a strong oxidation of the surface of the material being processed,” says Fidopiastis. “In most EtO processing, heat and moisture must be considered with respect to the oxidation of packaging materials. Additionally, pressure gradients must also be considered for the functionality of the product, like prefilled syringes.”
But Jason Voisinet, senior project coordinator at Ethox International Inc. (Buffalo, NY), says careful planning can even things out. “The impact on packaging can be overcome by reducing the rate of pressure change during the phases of the cycle,” he explains.
However, techniques employed to decrease turnaround time, known at Steris Isomedix Services as EO-Express and at Sterigenics as CycleOne, may increase stress on the package. In these processes, preconditioning, sterilization, and aeration are all performed in the sterilization chamber, rather than as separate processes. “With this all-in-one process, there are often more pressure changes throughout the cycle, and in some cases, higher levels of relative humidity, as compared to the conventional three-phase process,” Houghtling says. “These factors must be taken into account and be made part of process development and/or validation.”
Gamma radiation
With irradiation, the most popular being gamma, the impact is on the packaging material itself. But a wider range of compatible materials is available. “Even polypropylene films can be made more radiation compatible by axial orientation,” explains Karl Hemmerich, plant manager, Steris Isomedix Services.
Irradiation can accelerate the aging of packaging, sometimes causing cross-linking or other molecular-level changes of the material. In some radiation processing, the susceptibility of the material to heat must also be considered, says Fidopiastis. Also, when an active pharmaceutical ingredient (API) product is used, “interaction between the packaging material and the API must also be considered—specifically the potential of leachable byproducts of the packaging induced by the ionization of the packaging material and the effect of these byproducts on the API,” she adds. “Processes like our ExCell method can deliver precise dosage using automated conveyance, material handling, and process-control systems, with negligible impact on approved packaging choices.”
One of the benefits of radiation sterilization is that it is compatible with nonbreathable packaging. “This allows for both a wider selection of materials of choice for the package,” says Houghtling, “and with that, the selection in some cases of less-expensive packaging materials.” In addition, radiation can be used where EtO cannot—for products requiring a gas-impermeable package, such as bioabsorbable products, Houghtling says.
In addition, Hemmerich contends that radiation processes tend to be gentler than other methods and that a nonbreathable package may enhance sterility maintenance. “If I were to design the most robust package from an environmental incursion perspective, it would be radiation compatible,” he says.
E-beam
A radiation process that can be even gentler on packaging is electron-beam sterilization. Though gamma irradiation can penetrate greater densities, e-beam has a shorter turnaround time and may produce less degradation in both packaging and products, says Glenn M. Thibault, EVP and COO of Beam One LLC (San Diego). “E-beam is generally much kinder to the packaging, as well as to the products themselves,” says Thibault, explaining that products are in the radiation field for only seconds with e-beam processes, versus hours with gamma.
In addition, a gamma irradiator has to group products according to dose and may have to purge the cell between batches that use different doses. Some products may be irradiated at higher doses than they really require for the sake of efficiency. With e-beam, products requiring varying doses can be run back to back without purging the cell in between. This means that each product receives only the dose it truly needs, says Thibault.
With more materials suppliers adding radiation-stable resins to polymers or bluing agents to combat cosmetic yellowing of the package caused by radiation, the option becomes even more attractive. “There are a whole lot of materials that are now very good radiation-stable materials,” Thibault says. And because suppliers are seeing more demand for radiation-stable materials, the cost of these materials is coming down.
Though less popular currently than gamma irradiation, “E-beam can probably do better than 50% of all the sterile products on the market,” Thibault says. “It is a niche market out there, but it is growing. There’s a lot of interest in e-beam right now.”
Fidopiastis at Sterigenics concurs. “Having recently opened our seventh e-beam facility, located in Shanghai, there is a steadily growing market for this modality of sterilization.”
From EtO to E-Beam Sterilization Boston Scientific (Maple Grove, MN) has started using e-beam sterilization on some products, and it is testing new sterile barrier materials for use in the process. “We are currently using contract services for e-beam sterilization, but the technology is available for anyone to bring this in house,” says Tim Mlsna, director of packaging. Mlsna says e-beam sterilization will allow the adoption of film/film pouches, replacing those that use the more-costly Tyvek. “You have to make final decisions on packaging materials during your proposal and/or design phases. When selecting these materials, you need to evaluate all potential impacts. For instance, your bonding material is critical, as the intensity of e-beam sterilization can cause adhesives to become brittle,” he says. “When you are sealing the poly/poly structures, there is also a tendency for many of these materials to start to curl. This curling isn’t conducive to easy handling, and it makes it more difficult to inspect for good seals as product leaves your facility,” Mlsna says. “If you have a device that is going to be radiation sterilized, it may make sense to go to a film/film structure,” says DuPont Medical’s John Richard. “However, these formats are not without limitations particularly surrounding sterilization flexibility and product distribution. Designs incorporating porous packaging provide an MDM a broader range of future sterilization options without the need to redesign or validate a new package, while minimizing the potential for distribution-related recalls caused by atmospherically induced seal failures,” he says. —David Vaczek |
VHP
Another area of growing interest, says sales and marketing manager Larry Lachowski of Steris Corp. (Mentor, OH), is vaporized hydrogen peroxide (VHP) sterilization. Used in the pharmaceutical industry since the early 1990s, VHP sterilization is now also being used by the medical device industry. Lachowski cites the benefits of the process as rapid cycle times, no toxic residuals or carcinogenic by-products, broad material compatibility, low operating costs, fast turnaround, and no plasma phase.
The VHP MD sterilization system is designed as an in-house process. It can be easily integrated with the manufacturing and packaging operations, providing just-in-time sterilization. By using the VHP process in-house, a medical device company can lower sterilization costs and reduce costs of finished goods inventory and work in process (WIP).
The VHP MD sterilization process offered by Steris works well with most types of packaging, reports Lachowski, as long as the packaging has a breathable component, like Tyvek, to allow the hydrogen peroxide vapor to penetrate through the package and into the medical device. “A gas permeable pouch or lidded tray works well with VHP sterilization to provide an adequate level of sterilant penetration. Customers have not reported any undue stress on packaging by using VHP sterilization,” he says. “Packaging that is typically used for EtO sterilization is compatible with VHP.”
Design for sterilization
No matter which sterilization methods are chosen, they should be considered as early as the product design phase, say experts. And sometimes, the best idea is to design packaging compatible with multiple methods. “If a package is breathable (like Tyvek) and is radiation stabilized (as many are), both radiation and ethylene oxide have little or no effect on packaging,” says technical specialist Martell Winters of Nelson Laboratories (Salt Lake City). “If a package can handle radiation and be breathable, it will be a big benefit to customers who use both types of sterilization.”
“If this is done, the packaging does not dictate the selection of sterilization methodology, but instead it becomes a transparent factor. This allows the choice of sterilant to be based on other factors, like which one is the most cost-effective method of sterilization for the particular device in question,” says Houghtling.
And cost is certainly a factor. “Most medical device manufacturers are being forced more than ever to keep costs down,” says Brenda Sparks, account manager for Centurion Sterilization Services (Howell, MI). “You want to make sure that you are providing adequate protection and end-user satisfaction without adding extra layers of cost. For example, with EtO sterilization, most contract sterilizers bill by chamber space. If you add several layers of protection that are not needed, you are not only wasting dollars on packaging materials, but valuable chamber space. All of this adds to the bottom line.”
The key to choosing the right materials, design, and sterilization method—while keeping costs low—is addressing sterilization requirements early in the design review process, according to Voisinet. “Design review is a process more like ballet than a hockey game,” he explains. “It’s all about a system of controlled, planned events, rather than random accidents to create a final product.”
Packaging materials selection should therefore account for facilitating the intended sterilization process or at least be selected to minimize interfering with the sterilization process,” says Fidopiastis.
