4 Things to Consider When Designing Medical Packaging for E-beam Sterilization

Packaging design for medical devices is typically driven by the requirements of the product itself, as it should be, as well as how it will be used — and by whom — at the point of care.

Understanding how electron beam or e-beam sterilization is optimized, however, can help packaging engineers create packaging systems that deliver more flexibility and lower cost over the lifecycle of the product.

Here are four considerations packaging engineers should evaluate when designing packaging that will be e-beam sterilized.

1. E-beam is safe, scalable, sustainable.

E-beam is a well-understood and mature technology. Like ethylene oxide (EO) and gamma (both of which collectively serve 90% of single-use sterilization today), e-beam is also decades old and recognized by the Food and Drug Administration (FDA) as a Category A sterilization modality. That indicates that e-beam has a long history of safe and effective use on medical devices.

Recent environmental and litigation risks have plagued EO, while supply constraints have limited and stalled the growth of the gamma industry. Additionally, e-beam system throughput, stability, and sophistication have been significantly increased by the accelerator industry over the past decade, bringing the technology to a point where it is capable of delivering reliable large-scale sterilization capacity (a large facility may process many truckloads each day).

Thus, accelerator-based modalities like e-beam and X-ray are the only scalable and mature, FDA-accepted (especially e-beam) modalities that we expect to be able to grow with the scaling demand of the medical device market. Research indicates that e-beam is expected to grow at a compound annual growth rate of 8.5%.

E-beam is also highly sustainable (as clean as the grid power it uses) and much less expensive to deploy than X-ray. These aspects of accelerator-based technology make it an attractive terminal sterilization option for developing long-term production plans that seek to promote sterilization modality, vendor flexibility, and optimize economics.

2. Materials matter though.

At the packaging engineering stage of the project, we assume that product component material selection has been made, but packaging material selection (in both primary packaging and over-shipper selection) is yet to be defined.

Publicly available resources can help with packaging material selection for products to be e-beam sterilized:

• AAMI’s Technical Interchange Report (TIR) 17 provides a list of commonly used materials for medical devices and their packaging.

• Pacific Northwest Laboratory’s Team Nablo offers material irradiation performance research.

• NextBeam.com also has articles on material compatibility for e-beam.

Commonly used packaging materials have excellent radiation at common medical device maximum doses (such as 50 kiloGrays or kGy):

• Tyvek is commonly used in sterile barrier systems. Tyvek maintains its physical properties well above 50kGy, making it suitable for the vast majority of medical device sterilization applications.

• Cellulose (paperboard) is rarely a limiting factor in radiation sterilization. Corrugated board maintains its physical properties with doses in excess of 50kGy.

• Common polymers have good-to-excellent performance up to 50kGy, including polyethylene (PE); polycarbonate (can exhibit some yellowing at higher doses); polystyrene; polyvinyl chloride (PVC).

• Metals and ceramics of all kinds.

3. Geometry and orientation are factors.

While materials matter for all kinds of radiation sterilization (e-beam, gamma, and X-ray), geometry plays a much larger role in e-beam packaging design due to the limitations of e-beam penetration.

The stochastic nature of how the high-energy electrons generated in an e-beam facility undergo absorption in a non-homogeneous target, such as a shipper box containing medical devices, is a complex modeling problem. Fortunately, there are new computational tools out there that may be used to assess new products. These Virtual Dose Mapping (VDM) tools can use fully characterized CAD models of packaged devices to predict the “hot and cold” dose distribution that results from radiation processing.

However, in the absence of VDM tools, simple rules of thumb may be used to estimate e-beam performance. A two-sided 10MeV process will typically exhibit tolerable DUR (Dose Uniformity Ratio) performance if the maximum areal density of the package is kept under  8.5 grams/cm². Thus, a packaging engineer with access to CAD tools or rough device mass characteristics can estimate how much “worst-case” mass the electrons might have to pass through on their way through the package in any of the three axes that a shipper box might be presented to the beam.

What can a packaging engineer do with this information? If obtained early enough in the packaging design process, this data might be used to select or adjust the configuration of individual products inside their sterile barrier packaging such that a minimal areal density profile may be presented to a beam (subject to aforementioned ergonomic and/or usability constraints).

If later in packaging design — such as during shipper box configuration and selection — this information might be used to choose a configuration that could yield a much lower DUR. More specifically, this might lead to choosing configurations that preserve a “narrow” dimension that an e-beam could shoot through, rather than optimizing a package for minimum corrugated board consumption. A useful mental image is to think “pizza box” instead of “cube,” where the sterilization configuration is designed to enable an e-beam process with low DUR.

4. Processing families.

The sensitivity of e-beam to variation in product dimensions and the requirements for dose mapping might cause an engineer to wonder about how the qualification of similar products manufactured in different sizes (we will refer to this as a “product line”) can work.

For example, take a product line of implants that are offered in 18 different sizes for different-sized patients. This variation in size of products and packaging can present challenges in the sense that dose mapping each size of product in the line is not economically feasible.

As in other modalities, there are well-worn pathways to creating “processing families” by creating just a few dose maps for best/worst-case challenge conditions. Depending on the nature of the product and its variation, this approach can dramatically simplify e-beam qualification.

For example, NextBeam helped a client with more than 200 stock-keeping units (SKUs) for a set of similar devices cover the range of their products by creating just three processing families. In this case, through careful analysis of the products, we were able to select just five products for dose mapping and demonstrate that the results could be used to establish three process specifications — one for each processing family. In this way, we were able to reduce upfront qualification costs dramatically and put the client on a path to much simpler and more scalable processing operations.

I’ve prototyped a package. How do I get some test data?

Another e-beam advantage is rapid testing. Single-replicate test dose mapping and/or max dose testing can typically be done with less than an hour of machine time and, with a modern lab and well-trained dosimetry team, rapid, low-cost feedback is possible in days — not months, and typically at a cost point of $1,000 to $2,000.

Takeaway: It’s never too early to start thinking about sterilization.

Whether medical devices or fighter jets — the design and fielding of modern, complex, high-performance systems requires a great deal of not just design, but verification and validation as well.

As packaging design typically occurs later in the product development process, when many product design choices have already been made, there isn’t always an opportunity to make significant changes in product design or configuration. So while the considerations described above can still be useful tools, the best approach is to involve design-for-sterilization considerations as early as possible in the product and packaging design process. This can help to dramatically simplify production, distribution, and efficacy of a long-lived medical device product, saving millions in lifecycle costs and enhancing sustainability.