Originally Published MDDI October 2005
Cover Story: Packaging
Complex and comprehensive assessments are needed to
select the right high-barrier packaging material for devices
that are sensitive to moisture, oxygen, or light.
By Erik Swain
|Barrier packaging materials courtesy of Perfecseal (Oshkosh, WI), Mangar Industries Inc. (New Britain, PA), and Oliver Products (Grand Rapids, MI).
Photo by RONI RAMOS
(click to enlarge)
Basic packaging materials work great for basic medical devices. But more and more devices coming on the market, especially combination products, need protection from moisture, oxygen, or light. For those types of devices, packaging engineers have to look to materials that provide a stronger barrier than standard offerings.
The process isn't as simple as picking out a barrier material and going with it. First, an engineer has to determine whether there is a sensitivity issue. If there is, it must be quantified to find the level of protection needed. Then, the engineer needs to consult with packaging suppliers to determine which materials are available to provide adequate protection. The choices should be assessed in a variety of ways, including for manufacturability, functionality, sterilization implications, and, especially important in this day and age, for cost. And finally, physical tests must be conducted to ensure that the packaging material provides the needed protection.
If your company hasn't yet developed a product needing enhanced barrier protection, chances are it will eventually. “There probably is an increase in the number of devices and diagnostics that are sensitive to the normal environment,” says consultant Donald Barcan, president of Donbar Industries Inc. (DBI; Long Valley, NJ). “Device companies see these as very significant issues. The pipeline is constantly being infused with new materials and new laminations of current materials. Barrier packaging is one of the fastest-growing segments of the market.”
Confirming the Need
A device containing a drug or biologic is an obvious candidate for high-barrier packaging. But a number of newer resins are being used to make devices that may change properties when exposed to the environment for too long, says Ed Verkuilen. “Some of the ultra-high-molecular-weight products may have issues with sensitivity,” he says. Verkuilen is marketing manager of Rollprint Packaging Products Inc., based in Addison, IL.
Other likely candidates for barrier packaging are absorbable products, says Roger Allen, director of R&D and technical services for Mangar Industries Inc. (New Britain, PA). “For example, there are a number of orthopedic products made of molecules that get absorbed into the body and heal like bone,” he says.
To begin, packaging engineers should perform accelerated and real-time aging studies on the product to determine sensitivity. A good tactic is to consult with a supplier to come up with several possible barrier materials and test the product inside all of the candidates. Keep in mind, however, that these early tests are not a substitute for validation work with the final package selection.
Next, the results will have to be quantified to determine with some precision what level of barrier protection is required. Once the results are quantified, you are ready to select your material. It is tempting for cost reasons to pick a material that meets only the minimum requirements, but that may not always be wise.
“Often, you'll want to go a little over and be on the safe side, so you're not walking a fine line,” says Verkuilen. “If you get to the end of the validation and the package integrity is compromised at that point, you'll have to spend the time and money [to do the process] all over again.”
It may be possible to use a software system to help determine the appropriate barrier. For example, Amcor Flexibles (Mundelein, IL) has a simulation program called Black Box for that purpose. “It looks at the properties and requirements of the product and makes estimations of what the barrier level of the package will be,” says Chris Heezen, Amcor's director of regional sales.
Choosing the Material
There is a wide range of barrier material choices, and new products are coming on the market steadily.
Aluminum foil laminations provide the highest barrier for all three kinds of sensitivities. However, they are also the most expensive option, so they may not be the preference if you have a high-volume or commodity product. Also, the foil layer must be a minimum of 1 mil thick. A rule of thumb is that foils any thinner than that are susceptible to pinholes.
Aside from cost, there are other reasons that foil, despite its high barrier properties, may not be the right material for a particular package. If a device company has committed to EtO sterilization, it cannot use an all-foil package because foil is not porous. And the firm may demand the use of a transparent material. “Sometimes customers want transparency as a marketing tool, sometimes they want it as a quality tool, and sometimes they want it for other reasons,” says Geoff Pavey, senior product and process development engineer for Oliver Products (Grand Rapids, MI). “It may be needed for product identification or to see physical degradation.”
In addition, he says, some rigid packages may be unable to have lids made of nonporous material. “Depending on the amount of headspace, a nonporous lid could pop open during air transportation,” he says. The same effect can show up during accelerated aging tests, he notes.
|Rollprint packaging materials are used to make blood test kits. Other types of packages (inset) are made with foil covers.
(click to enlarge)
A hybrid design that allows for EtO sterilization of foil packages is becoming more popular. “These have a vent made of Tyvek or another porous material on one end, and the rest of the package is a foil laminate,” says Allen. “You load the product in, seal the Tyvek, sterilize the package with EtO, reseal the foil, and cut the Tyvek off.” The resulting package has a foil barrier in its entirety, but was sterilized by EtO. This design can be used for products such as drug-eluting stents that need the highest level of barrier protection but do not fare well with gamma sterilization.
Most products requiring high-barrier materials can withstand gamma radiation, so that is the most frequent choice of sterilization. Autoclave and dry heat are sometimes appropriate as well, says Verkuilen. In such cases, however, “the sealant materials need higher thermal resistance, so you may need to select a different sealant layer.”
If foil is not required or if it is deemed too costly, there are a number of high-barrier films available. Often they are coated with aluminum oxide, silica oxide, metallized polymers, or polyvinylidene chloride. Sometimes they have barrier properties built in, such as in the cases of nylon, Surlyn, or polychlorotrifluoroethylene (PCTFE). Many of these materials are used in pharmaceutical packaging and may be appropriate for combination products.
One example is Aclar Flex, a new formulation of PCTFE from Honeywell (Morris Plains, NJ). The Aclar brand has been a long-time staple of high-barrier pharmaceutical packaging. In April 2005, the company launched an application geared to flexible medical applications, including overwraps, pouches, and lidding. In addition to its high barrier properties, Aclar is considered a fit for healthcare applications because of its chemical stability. It is biochemically inert, chemical resistant, nonflammable, and free of plasticizers and stabilizers.
Rollprint offers a line called ClearFoil that aims for a similar goal—barrier protection nearly as good as foil in a transparent package. “It is ideal for applications such as tissue products, where the surgeon needs to see the size and shape of the product before he opens the package,” says Verkuilen. The company has developed dozens of grades and continues to come up with new ones from time to time.
Some suppliers offer films with built-in desiccants, which absorb moisture while the package sits on a shelf.
For light sensitivity, alterations to conventional films might be able to do the trick. “Light sensitivity can be abated with pigments in the film that make it opaque,” explains Barcan.
Another common approach is to use a UV inhibitor that does not compromise clarity, says Pavey. For example, Mangar offers a UV-inhibiting film called Stablock that is applied to a polyester, Allen says.
Packaging engineers might also want to design in features that indicate when the device has been exposed to unacceptable levels of moisture, oxygen, or light. “I have developed sterile-device package designs that provide a visual affirmation that the package has not been compromised,” says Barcan. “If a package goes soft, the device or diagnostic should not be used, because the package has been compromised. This visual indication is true for both breach of sterility and sensitivity.”
Storage and Handling
Combination products have product-package interface problems that traditional devices do not usually need to overcome. In some cases, this means they cannot withstand exposure to extremely hot or cold temperatures. For those instances, cold-chain management principles must be incorporated into the package design, says consultant Douglas Stockdale, president of Stockdale Associates Inc. (Rancho Santa Margarita, CA).
“You may have to understand how to handle products that can't get too cold or too hot. These are not things that medical device packaging engineers are used to facing,” he says. “They need to come up to speed on it. The problem is that there is no guidance per se. Instead, there is a Parenteral Drug Association (PDA) working committee that is making up de facto standards for all this.” PDA (Bethesda, MD) was started as an organization for those who develop parenteral drugs, but it has expanded into the device arena and other areas in recent years.
“This could be a situation like what we saw with aseptic processing: There was a PDA guidance before an FDA guidance,” says Stockdale. “The companies that have to deal with this are trying to self-police. Even the Europeans don't really have [a standard] yet.”
Even if a full-fledged cold-chain management program is not needed, engineers may need to test the packaged product. It is important to make sure sterility and sensitivity are not compromised during shipping and handling, Heezen says. “Not all materials act the same. They may not have the same durability or resistance to flex crack.”
Another consideration is package-processing equipment. Engineers must ensure that it works as well for high-barrier materials as it does for conventional materials. “As new materials are developed, it cannot be automatically concluded that the current pouch-making or sealing equipment will be acceptable,” says Barcan.
After all these issues are considered, the packaged product must be put through a validation protocol. “Certainly all the normal validation issues of sealing and process control apply,” Barcan says. “However, the efficacy of the device needs detailed analysis based on shelf-life and expiration dating. Because of the device's sensitivity to moisture, oxygen, or light, the company needs to demonstrate that the packaging and device or diagnostic performs to specifications.”
Stockdale agrees. “In these situations, validation gets more complex, because you don't know just by checking for sterility whether there was a failure or not,” he says. “You may need to implement the types of validation programs that people in drugs and biologics do. You'll need to do more verification of product-package interface, for one.”
When a sensitivity issue may be involved, a packaging engineer's work gets more complex. More evaluation of the device must be done before the design process can begin. More thought must go into selecting the appropriate materials. Design and sterilization issues may impose constraints that are not present with other products. And the validation protocol will likely be more comprehensive. But there are plenty of appropriate materials available, and suppliers and consultants with experience in matching them up with moisture-, oxygen-, or light-sensitive devices are available. Don't be afraid to seek assistance.
Copyright ©2005 Medical Device & Diagnostic Industry