Customization Rules

In addition to EtO processing, Ethox International manufactures and packages medical devices.

As standard as it may seem, sterilization is increasingly becoming a customized process. Of course, when it comes to packaging, the basics are pretty routine and predictable—ethylene oxide and vaporized hydrogen peroxide need breathable packaging so that the sterilants can reach the product, and radiation sterilization can degrade some types of plastic, so its use may be limited to certain materials.

But that’s where the routine ends. Thanks to advancements in parametric and dosimetric release, sterilization can often be expedited, based on product needs and manufacturer budgets. Cycles may also be adjusted to accommodate temperature-sensitive or fragile products. These adjustments are all part of an effort by sterilization service providers to optimize the sterilization process to make it affordable, suitable, and just-in-time for product and market needs.

Packaging designers need to consider such customization. Packaging for an EtO-sterilizable product may no longer just require a breathable component—it may also need to withstand the rigors of expedited processes, such as vacuum and high temperature.
And even if a firm’s sterilization processes tend to be more on the routine side, experts say packaging always must be developed with sterilization in mind. To that end, many service providers offer package design consultation.

REVIEW YOUR DESIGN

Gary Benson, director of sales, laboratory and sterilization services, for Ethox International (Buffalo, NY), says medical device companies should be considering package design and sterilization requirements during a product’s design review. Typically, however, packaging is developed “after the design of a product has been finalized,” he says.

But, “just as you must be concerned about the integrity of the product and its functionality, you must have the same considerations for the package,” advises Betty Howard, manager of the Gamma TechTeam at Steris Isomedix Services (Mentor, OH). “Leaks, tears, brittle seals—or the opposite, too tight a seal—may result from the sterilization method, so [packaging] must be evaluated [after sterilization]. Even if you set a dose or design a cycle perfectly, the product sterility will only be intact while it is in the sterilizer itself if the package does not remain intact.”

Adds Jack Fitzpatrick, director of business development for Sterigenics (Oak Brook, IL): “Every change to a package must be evaluated in terms of performance during sterilization, even corrugated packaging. The sterilization process is especially hard on the package.”

Ideally, product design would converge with sterilization methodology selection and package development at about the same time. Special product needs could be met, such as the development of a sterilization process and packaging system for a temperature- or moisture-sensitive product. Or specific marketing demands may need addressing, such as a long shelf life of five years, which may require the use of materials that can survive sterilization, aging, and shipping, say Benson.

TIME CRUNCH

Trouble is, companies may not be leaving enough time for comprehensive evaluations that involve product design, packaging, and sterilization, says Benson. “There is pressure to deliver new innovative products that will win market share,” he says.

Benson recounts a conversation Ethox’s president had with a large manufacturer of cardiovascular products: “The manufacturer said that 80% of its revenue is generated by products that didn’t exist two years ago. The pressure to deliver products, therefore, is increasing.”

As a result, Benson hears this question all the time: “How fast can you validate packaging? I needed it yesterday.” As a full-service FDA-registered device manufacturer, packager, and sterilizer, Ethox is often able to consolidate steps and eliminate some of the red tape in getting a product completed, without any compromise to compliance, but it still takes time, he says.

And the process of considering product design, sterilization methodology, and package development isn’t linear, by any stretch. In fact, even though sterilization and packaging should come up during the design phase, their development must continue and be constantly evaluated, even after the final stages of product manufacturing. “Since packaging represents the barrier between sterile and unsterile, all packaging must be tested under the conditions that the final product will be sterilized with,” says Howard. “For this reason, as well as the possible contribution of bioburden from the package itself, all dose setting is done on final product in its final packaging. This ensures that the proper dose or conditions are set and that the product is functional with the sterile barrier intact post sterilization.”

PITCHING IN

Sterilization service providers don’t want to see packages fail, so many of them are lending a hand when needed. In addition to staffing product design and quality assurance engineers, Ethox has a team of package designers. “We help companies determine issues such as, is there enough breathable space for sterilization? Could labeling be in the way of breathable packaging?” explains Benson.

Sterigenics offers consulting through its SteriPro division, led by Niki Fidopiastis, director, sterilization consulting group. The division offers package design and redesign, which includes package qualification and validation as well as shelf life qualification. “SteriPro is being used by small- to mid-size firms that don’t have expertise in house,” says Fitzpatrick. Through such consultation, Fitzpatrick says that consultants help companies fully evaluate the effects of terminal sterilization. For example, “terminal sterilization is often found to be too hot for certain biologicals, or they just can’t cope with the residuals. Cold cycles, therefore, may be needed.”

In other cases, density may be an issue. “Customers want to maximize packing density to ship as many products as possible,” Fitzpatrick says. “SteriPro can help them develop the appropriate cycle for the customer and the product.”

BeamOne LLC (San Diego, CA), a firm offering electron beam sterilization, conducts a detailed study of the dose distribution within a product box. During this dose map study, shipping boxes as well as inner packages are opened and dosimeters are placed on products throughout the packages to measure the radiation doses that reach critical areas. According to the firm, this study enables the company to correlate these doses to the external reference dose monitor used during routine processing.

Even seemingly stock items such as biological indicators can’t be left to chance. Dan Dwyer, sales and marketing for Raven Biological Laboratories Inc. (Omaha, NE), explains that some of their work in medical device sterilization involves a custom solution. The company offers a range of indicators, which include Prospore Ampoules for steam processing and ProTest self-contained units consisting of a plastic container with cap, a crushable glass ampule with recovery media, and a paper disc inoculated with spores for EtO and steam processing. Indicator strips and labels are also available.

Dwyer recounts an instance in which a manufacturer of a device with tubing asked whether the strips could be cut small enough to slip into the tubing to indicate sterilant penetration. Wary of such use, Dwyer says that Raven developed an alternative: woven cotton threads that can be inoculated with any organism the firm provides and placed into small openings and lumens. Steel wires are another option. Given their rigidity, they can be easily retrieved from condensation-filled areas or looped if needed.

Given the results of such consultation, customization can help packaging professionals develop the best design, for both primary and secondary packages. As routine as sterilization may appear to be, its processes and their effect on packaging require close attention.