Medical Device Link.

Originally Published PMPN March 2003

Sterilization

Package engineers can take steps to ensure their designs withstand expedited sterilization processes and ultimately 
meet speed-to-market demands.

by Lori Bryan, Contributing Editor

Engineers of packaging for medical devices and pharmaceuticals can rest assured that the sterilization technologies they’re familiar with are fairly constant. That is, ethylene oxide (EtO), gamma, E-beam, steam, and gas plasma promise to remain fundamentally the same, at least for the foreseeable future. However, sterilization professionals are making subtle refinements—changes packaging engineers need to be aware of, should they affect design considerations.

With EtO, for example, much of the current focus is on expediting the process. To take time out of the supply chain and increase speed to market, contract sterilization providers are finding new ways to deliver the necessary lethality faster and then to remove the residual gases more quickly. Engineers and the packages they create stand only to benefit from understanding any potential changes in temperature, vacuum stress, and other critical variables that may accompany such process improvements. 

While advances like expedited EtO may add a bit more work to the ster-ilization learning curve, package en-gineers needn’t worry. After all, the things they need to be evaluating for a given package—for example, material limitations, the impact of a particular sterilization method on a package’s seals, issues of drug stability—haven’t changed. The key difference is that, in light of process improvements, package engineers may find they have new questions about familiar technologies.

The answers are out there, say experts. They recommend that package engineers consider the following action items for securing the information they need.

Communicate with contract sterilizers about process im-provements. Staying abreast of the changes that contract sterilizers make to existing sterilization methods can help package engineers avoid pitfalls. 

Modifications package engineers can expect to see include “better mechanisms to control processes, to quantify processes, and, in many cases, to shorten processes to times that are more realistic,” says Gregg Mosley, president of Biotest Laboratories (Minneapolis).

An example of this is an expedited EtO sterilization technology in development at Sterigenics, a member of the IBA Group (Chicago). “With the market pushed to get products faster, you’re now seeing innovation take root,” says Bill Young, the firm’s senior director 
of medical sterilization technology. Sterigenics’ new service, CycleOne— available at each of the company’s facilities beginning at various times 
this year—sterilizes and processes in one chamber in one day, unlike more-traditional EtO cycles, which can take up to 12 days using multiple chambers. 

“Oftentimes in processes, anywhere from 30 to 80% of the time required for sterilization using ethylene oxide is tied up in the removal of [those] gases from the package,” Young adds. “We’ve found ways to shrink that time based on accepted regulatory practices, ISO guidelines, and FDA inspection criteria.”

Package engineers who understand process improvements from the outset of a project will be best prepared for creating packages that can hold up during sterilization, whatever the chosen method. With information comes possibility, as Sterigenics’ Young illuminates: “We’ve been able to tailor CycleOne in several ways for clients who may have packaging that can’t withstand certain aspects of [the service].” 

Select packaging materials carefully. Whether planning for an expedited process or a longer one, package engineers must evaluate materials thoroughly and understand their limitations. This includes (and is in no way limited to) considering how effective a material will be in presenting a product, what residuals a material may hold if subjected to EtO, and how a material will respond to gamma irradiation or high-temperature steam sterilization. The answers to such questions should reveal the right sterilization method for a particular product and its packaging.

“Engineers being as knowledgeable as they can be when buying materials is certainly going to aid in the pro-cess,” says Gary Benson, laboratory manager for Ethox Corp. (Buffalo, NY). Much of that know-how comes from having a good relationship with the material and coating supplier. Up front, Benson says, vendors should be supplying manufacturers with information on tensile strengths, flow rates, and sealing properties, for example. 

Such data should be easy to access, especially from innovative suppliers that are eager to demonstrate how they’ve enhanced materials for the rigors of sterilization. For example, “many of the Tyveks [available] now are heat-stable for steam sterilization processes at approximately 250°F,” says Mosley of Biotest Laboratories. Also, advances in different types of adhesives, Mosley says, are allowing for more uniformity of seals and greater seal strengths.

Of course, all the preliminary re-search and bolstered materials in the world won’t prevent problems from cropping up, and package engineers must be willing to work through them.

Contract sterilizers, together with their clients, deal with such glitches routinely; Ethox’s Benson recalls a particular event: “[A group of] engineers, in trying to work with the needs of physicians, designed fairly complex holding packages for small eye-implant devices.” As it turned out, Benson says, “the packages greatly increased the quarantine time necessary to eliminate residuals poststerilization.”
Take a team approach. Package engineers should not be left alone to face the many key considerations from material evaluation to stability testing and palletization.

“Very often, packaging engineers focus on two or three particular concerns and may have little experience with something else, whether it be breathability or degradation or air exchange,” says Mosley. “But others in sterilization or microbiology or quality may have quite a bit of experience with it, and bringing in those individuals fairly early for some of the design considerations” can help prevent a company from going down a wrong path with a product/package, he says.

Sterigenics’ Young agrees. “It’s very important that package engineers are part of an [internal] cooperative team—a development team—or that they have access to knowledgeable professionals on the outside.”

Group examination of the potential sterilization method is paramount. “Once a concept has been initiated, the package engineers, as well as the design engineers of the product itself, should have immediate contact with experts in sterilization who understand the limitations of the method they’re going to use and what the minimum criteria are for successful sterilization,” says Ethox’s Benson. 

Additionally, package engineers should seek advice on test methods from an in-house or contract laboratory. This is especially important for “[companies] going for expiration dating or shelf-life-stability testing or determining package integrity and barrier properties,” says Benson. “The primary focus is saving money in the long run. You’d rather do it right once than have to repeat it and increase your timeline.”

Consider hiring a consultant. In an increasingly complex industry, package engineers can’t necessarily expect to find all the answers to their questions within their companies. 

Take sterilization of a densely packaged device kit, for instance. “As [such] kits have become more and more intricate, and speed to market has become more and more crucial, penetration into the center of the load has become more difficult,” says Young. Add drug items to those kits, he explains, and your options for sterilizing that kit narrow.

Looking to outside experts, whether they’re independent consultants or part of a contract sterilizer’s outfit, may prove expensive indeed. But de-pending on the situation, a company could incur greater costs in the long run by not getting the expertise it needs at the outset of a project. “Costs may seem prohibitive, but that’s usually considering the best-case scenario rather than the worst-case scenario,” says Mosley. “[When] you’re well into the course of the plan before you realize you have a problem, the cost can double or triple,” Mosley says. 

Once the decision to hire a consultant is made, finding a person competent for the job shouldn’t be difficult. However, finding one who understands a package engineer’s particular innovation could be. “I would advise package engineers to look carefully at the [product/package combination] with their sterilization supplier and see whether the supplier can recommend some consultants who would be well matched,” Young says. 

Such matches are being made, perhaps more than ever before. “In our business, from a packaging standpoint, we’ve seen a general surge in [companies] asking for consulting services,” says Benson of Ethox Corp. More specifically, he adds, “we’ve seen an increase in the number of requests for package-integrity type testing.” 

Sterigenics’ SteriPro group of industry consultants works with a network of industry experts to advise clients on sterilization effects and requirements. 

Get and stay educated. Mosley says this is particularly crucial in today’s greatly expanded industry. “The industry has grown so rapidly that the number of [people] whom I’d call true experts has decreased proportionately,” says Mosley. “Also, a lot of the experts—people who’ve [worked in the industry] for 20 or 30 years— are retiring.” Consequently, “sometimes we have people who don’t have that background of experience, and they can’t find anyone who can help them sort out their problems in the timeline they’re under.”

Interactive educational courses covering standards, validation requirements, and the like can be especially helpful. “Instructors simply can’t address all of the problems and unique situations they’ve seen,” Mosley says. “So more-interactive seminars that allow a lot of questions are usually very good; when one person has a question, very often it will apply to several other people.” 

Becoming members in standards-making organizations also brings package engineers and sterilization experts together. “Packaging engineers or scientists—whatever their level of involvement from a sterilization standpoint—should be involved in AAMI and ASTM and as many committees as they can be,” says Ethox’s Benson. “That way it’s not a small group that makes decisions on how standards are written, but rather many people who’ve seen many situations,” he says. 

For information on continuing education and committee membership in AAMI (the Association for the Advancement of Medical Instrumentation; Arlington, VA) and ASTM International (the American Society for Testing and Materials; West Conshohocken, PA), visit the organizations on their respective Web sites at www.aami.org and www.astm.org.  

Package engineers should understand refinements to existing sterilization processes and how they may affect package designs. With so much emphasis on just-in-time delivery of life-enhancing and lifesaving pharmaceuticals and medical devices, package engineers and their partners haven’t a moment to waste. 

Copyright ©2003 Pharmaceutical & Medical Packaging News