The right choice for a medical package depends on an understanding of the effects materials and sterilization processes have on one another.
By Erik Swain, Senior Editor
Choosing the right sterilization method for your medical package is not something to be considered lightly. The selection of packaging materials and coatings, and in some cases the actual package design, often determines which kinds of sterilization will work well, which will work but not run optimally, and which cannot be used at all.
Some considerations, such as only using porous packaging materials with ethylene oxide (EtO), are obvious. Others are not, and new developments in a particular sterilization technology can challenge basic assumptions about material and processing choices.
"We have seen customers' interest in evaluating and selecting the right packaging materials escalate," says Bruce Schullo, vice president and general manager of analytical laboratories for IBA Medical Sterilization & Analytical Labs (Chicago). "Customers, concerned with improving quality and reducing costs, are asking us to assist them in determining process capability requirements and identifying which packaging materials are best suited for their sterilization method."
Here are some developments to keep in mind. However, experts say, make sure to consult your packaging material, coating, and sterilization suppliers regarding specific compatibility issues before undertaking a project.
With EtO, "the major concerns are the penetration of the sterilizing agent and the ease of removing the air during the sterilization process, particular during pre-EtO injection phases," says Gregg Mosley, president of Biotest Laboratories Inc. (Minneapolis). "Also, you have to consider whether the product and the package are a good fit for removing the residuals deposited by EtO. Polycarbonates, polysulfones, epoxy materials, and composite products often can present some problems with residual outgassing."
Frequently, says Karl Hemmerich, manager of plant operations and technical adviser for Steris Isomedix (Mentor, OH), "the overall package design is more of an issue than the materials involved. For example, if you attempt to put too much into a package, you may not give it the opportunity to breathe."
Aside from that, "EtO is pretty flexible as a sterilant," says Schullo. "The cycles we run are typically between 110° and 130°F, which is well below the melting temperature of the majority of packaging materials."
New developments are allowing for better gauging of the parameters of an EtO cycle, and better information at one's disposal could lead to an easier decision-making process in selecting packaging materials.
For example, Cosmed Group Inc. (Queensbury, NY) has developed a new sterilization technology that uses in-chamber processing for enhanced preconditioning and super-accelerated aeration, says Clark W. Houghtling, Cosmed's vice president of technical affairs. When combined with parametric release, the process allows the product to be sterilized and released to market in 1 day rather than the 10 to 14 days that had been typical with EtO, explains Houghtling.
As another example, IBA has been using mathematical models and new technology that allow for more accurate measurements of gas concentration, temperature, humidity, and other parameters to redesign sterilization cycles for customers, Schullo says. These scientific tactics have resulted in a number of efficiency improvements such as the elimination of aeration hold times and the establishment of parametric release processes that meet the requirements of ISO 11135/EN 550. "The parametric release process, coupled with our reengineering strategies, will allow companies to release their product to market directly after sterilization," he says.
Regardless of how advanced an EtO process may be, the correct coating choice will likely be crucial to its effectiveness. "If you are using fully coated Tyvek, outgassing can be reduced, which extends quarantine time," Mosley says. "Zone-coated Tyvek is better whenever possible."
Using a thin header strip of Tyvek or a small Tyvek patch on an otherwise all-film pouch is a way to improve barrier properties while still using EtO, but the trade-off is a lack of breathability, which can "prolong the cycle rather extensively," Mosley says. Cosmed's Houghtling agrees: "The more surface area there is of breathable material, the quicker you can get the EtO out of the package and the lower the residual level will be, which will result in a faster turnaround time."
If foils are to be used with EtO, there must be a second sealing step after sterilization and aeration to form a hermetic seal on the foil laminate barrier, says James Whitbourne, president of STS DuoTek Inc. (Rush, NY).
Another finding, Mosley says, is that a closed-cell polyurethane foam used inside trays "would shrink under deep vacuum cycles and not restore to its original size. That was a surprise."
Humidity settings are also a factor in EtO applications, says Jonathan Wallace, quality assurance manager at Sterilization Services Inc. (Atlanta). "Between 40 and 80% relative humidity is considered a good range," he says. "If it's too high, you will get condensation."
It is well known that gamma-radiation sterilization is not compatible with polypropylene or Teflon. In some cases, it is not compatible with rigid polyvinyl chloride either. It causes such materials to discolor and sometimes to become brittle.
What may not be as well known is that these materials are more susceptible to these problems when used as packaging films than when used on the devices themselves. The reason, Hemmerich says, is the larger surface area relative to the thickness. "Oxygen-directed breakdown is more severe in a film format than it is in a thicker format," he says.
For porous materials, Tyvek is more compatible than paper, in part because gamma sterilization can reduce tensile strength by as much as 20%. "Paper is not terrible, but it is a cellulose and it does break down," Hemmerich says. "You would have to use a quality paper to be able to use gamma sterilization. Reprocessed paper is not recommended nor are multiple sterilizations on paper. It will discolor and embrittle slightly."
Most other packaging materials, including polyesters and nylons, do fine with gamma radiation. According to a chart accompanying the "Polymer Materials Selection for Radiation-Sterilized Products" article—published in the February 2000 issue of Medical Device & Diagnostic Industry, a sister publication to PMP News—gamma works particularly well with polystyrenes, most polyethylenes, and most polyurethanes. And heat resistance is rarely an issue, as a typical gamma cycle runs just 10°–20°F above room temperature.
Another thing to watch for, says Hemmerich, is that "cross-linking may be enhanced in the seal material, so the seal may not open as easily as before. It depends on what adhesive you use." Furthermore, says Mosley, occasionally there are compatibility problems with coating materials, especially those used on foil pouches.
Another form of radiation sterilization, E-beam sterilization, has similar compatibility issues to gamma. With this form, a package that fits snugly around the product is advised because "if you can reduce the amount of air in the package, you reduce the chances that it will inflate during sterilization," says Harry L. Shaffer, vice president of technology for Titan Scan Technologies (Denver).
Also, he notes, "the higher the dose rate, the faster you can apply the dose and the fewer material effects you are going to get." High energy levels are required to penetrate certain rigid plastics.
Shaffer says that because ionizations occur much faster in E-beam than in other forms of radiation, E-beam has fewer effects on plastic than gamma and x-ray. Hemmerich says, however, that the effects on packaging films are pretty much the same as gamma because "oxygen is always there because of the large surface area."
Steam sterilization can present compatibility problems because of moisture and temperature, which is higher than most other forms of sterilization. A standard cycle is 250°F, although it can run as low as 212°F if a user is willing to give it more time.
"The steam temperature challenges many of the glass transition temperatures of medical packaging materials," says Hemmerich. "And a lot of materials, if they have any residual stress at all, tend to release stress, and you end up with distorted packaging. Paper and polyester work fine, and Tyvek can perform fairly well, but vinyls will distort on you. It can also be challenging if certain sealants are involved."
Foils are not compatible with steam sterilization, because the moisture cannot penetrate them, says Whitbourne.
One factor to consider, Mosley says, is whether a gravity or prevacuum process is being used. "If it's gravity, you don't want air entrapment between the package and the product. If that happens, it may not deliver the efficacy of sterilization you expect," he says. "If it's prevacuum, make sure you're using a packaging material that can withstand a very rapid evacuation process."
Because of the moisture involved, the compatibility with print inks is an issue with steam sterilization, but any vendor who supplies steam-compatible material should have already tested the inks, Whitbourne says.
Like EtO, hydrogen peroxide gas plasma must be used with porous packaging, and the choice is usually Tyvek. John Simmons, business director for Advanced Sterilization Products (ASP; Irvine, CA), a Johnson & Johnson company, notes, "for products that require a vapor barrier like polylactic acid sutures, for example, you can use a foil or other barrier material with a Tyvek header. After the sterilization and evacuation, the manufacturer removes the Tyvek header, and since the plasma phase breaks down the peroxide to water and oxygen, there are virtually no residuals."
It is not advisable to use paper in gas plasma sterilization because of reactivity with cellulose, Hemmerich says. "It was found that cellulose absorbed the sterilant material and you didn't even get a sterilization cycle. But other basic materials work well."
Gas plasma sterilizers are now available in larger sizes than they had been previously, Simmons says. When the technology first emerged, it mainly entailed the retrofitting of smaller sterilizers used in hospitals. But now that it has become more established, completely new GMP-compliant ones are being built, he explains. ASP's entries are 7.3 cu ft and 30 cu ft.
X-ray sterilization is still an experimental technology. It is somewhat slower than E-beam, but unlike other forms of radiation sterilization, it can be used to sterilize entire pallets of packages. So far in testing, material compatibility problems have not surfaced, but it is too early to tell whether that will remain the case, Schullo says. "If x-ray turns out to be compatible with more materials than gamma and E-beam, it will become a new sterilization alternative for the industry," he says.
While x-ray processing uses more energy than E-beam, its eventual acceptance may come down to cost considerations. Currently, it has a poor conversion rate, producing 5–10 cents of energy for every dollar of energy put in, says Hemmerich.
Whether you select packaging materials based on compatibility with a sterilization method in place or select a sterilization method based on compatibility with packaging materials in place, it is important to understand the effects they have on each other. It is also important to keep pace with changes in sterilization technology, as those could prompt a rethinking of packaging materials. As long as communication is maintained between device manufacturers, packaging and coating material suppliers, and sterilization providers, these understandings can be attained.