How you choose to sterilize a medical part can have negative consequences, unless you’re using 
current technology to gauge the effects.

The process of sterilization is an essential part of manufacturing many medical devices and components for those devices. Different methods can be used, all with the objective of killing potentially harmful bacteria, viruses, fungi, and spores, collectively referred to as “bioburden.”

As the polymer content in medical devices increases, the effects of different types of sterilization on these polymers must be understood. While there are many different approaches that achieve a sterile product, the three that are predominantly in use for medical devices are autoclave/steam, ethylene oxide, and high-energy radiation methods that include gamma and electron beam. While ethylene oxide has dominated the industry, gamma and electron beam are gaining traction due to their efficiency and an increase in available capacity.

Studies on the effect of radiation sterilization on polymer properties were performed in the mid-1990s when the technique was still relatively new for polymers and the medical device industry was the primary area of interest. A publication that is still cited as the benchmark, designated as TIR17, provided a list of various polymers and the upper limits of radiation that each material could withstand before exhibiting a measurable loss in mechanical performance. It was published in 1997, although an examination of the tables shows that some of the data were generated as early as the mid-1970s and pertain to products such as packaging, closures, and aerospace components.

Figures 1 and 2 show the tables within that document that captured data for a wide range of polymers and included appropriate caveats. The study referred to gamma, electron beam, and X-rays collectively as radiation and made no real distinctions between the methods when profiling the stability of the various polymers. However, some of the cited source material states that sterilization was conducted using gamma radiation from cobalt-60.

Out of the studies came some general guidelines for what works and what does not when sterilizing with radiation. There were some cautionary notes. For example, acetals, PTFE, and unstabilized grades of polypropylene (PP) were found to degrade rapidly when exposed to the doses that would typically be used in the healthcare industry. These tend to fall in the range of 30-60 kilograys (kGy).

The acronym APT (acetal, polypropylene, Teflon) was created to remind users of the three materials that they should be particularly wary of when using radiation to sterilize products. These concerns have been borne out by experience, and the concerted efforts on the part of the PP industry to boost the resistance of this polymer to degradation at the hands of gamma- and electron-beam sterilization attest to the concerns that existed when early use of PP materials led to rapid and dramatic embrittlement. Observations were also made regarding color changes in some polymers that, while cosmetically objectionable, did not necessarily alter the mechanical properties of the material.

But overall, the picture that emerged was of a class of materials that generally performed well in the environment of radiation sterilization. Using as a benchmark a 25% reduction in ultimate elongation, nearly 20 polymer families were cited as capable of absorbing doses equal to or in excess of 1000 kGy. Another dozen were listed at or above 100 kGy, and only the aforementioned members of the APT family, along with fluorinated ethylene propylene (FEP), fell below 50 kGy. The study provided a level of confidence to the medical device industry and its suppliers that high-energy radiation techniques would be viable for a wide range of plastic components.

Problems with silicone sterilization
But as the industry has grown and a greater variety of products have been developed, some concerns have arisen that were not foreshadowed in the original studies. Silicones are used increasingly as the elastomer of choice in medical devices, and the ability to injection mold this thermosetting elastomer into intricate shapes in dedicated equipment has accelerated its use. Silicone is listed in the 1997 study as having good radiation stability, and Figure 2 shows an exposure limit of 80 kGy.

Caveats indicate that phenyl-methyl polymers are superior to methyl silicones, platinum-cured systems will perform better than peroxide-cured systems, and that full curing is important to avoid what are termed “post-irradiation effects.” This is a nice way of saying that silicones undergo some crosslinking during gamma irradiation.

However, when a high level of mechanical performance is expected from a component, the generic disposition can be a poor predictor of performance. During development of a medical device designed to hold fluids at elevated pressures, a subassembly produced from a polycarbonate (PC) housing with a mating silicone part acting as a seal passed pressure testing before gamma sterilization.

After sterilization, though, changes in the assembly that were traced to the silicone caused the part to fail the pressure test. It was difficult to determine if the loss in performance was strictly related to dimensional changes due to residual crosslinking or if some degradation had occurred. Replacing the silicone with a polyurethane solved the problem. This change was driven by previous experiences with silicone that had shown the material to be marginal in irradiated products.

Combatting ESC in PC
A greater concern has been observed with semirigid thermoplastics. PC is used extensively in medical devices. It is valued for its dimensional stability, clarity, and toughness. However, it is also susceptible to environmental stress cracking (ESC). This is a frequent failure mechanism in medical devices due to the heavy reliance on amorphous polymers and the ubiquitous presence of a wide range of chemicals that can promote ESC. These include solvents used in the assembly process, plasticizers in flexible components, chemicals used to sterilize and clean the manufacturing and application environment, and even bodily fluids.

One of the key drivers in the short- and long-term performance of any polymer is molecular weight. The primary mechanism that has been identified as the source of property loss during radiation sterilization is chain scission, the process of breaking polymer chains and thus reducing the average molecular weight of the polymer.

The tables in Figures 1 and 2 suggest that PC would be virtually impervious to this process, given that it can supposedly absorb 1000 kGy with only a 25% loss in ultimate elongation. However, mechanical tests on products molded in PC have consistently shown a small but statistically significant decline in strength, even when the materials used were gamma-resistant compounds.

This loss in short-term performance has even greater consequences when long-term properties are considered. Long-term performance is sometimes not considered because the actual time that the product is in use may be very short. This is particularly true for one-time-use disposable products. Recall, though, that assemblies may remain in their original packaging on the shelf for months or even years. Stresses associated with the assembly will produce creep and if the assembly contains a material such as flexible PVC, the plasticizers present in the vinyl can combine with these stresses to produce ESC. The best defense against ESC, from a polymer property standpoint, is high molecular weight.

One of the simplest ways to measure relative changes in the average molecular weight of PC is through melt flow rate (MFR) testing. When these tests were performed on a series of samples that began with the raw material and tracked the polymer through molding and sterilization, it was shown that gamma and electron-beam sterilization both produce measurable increases in MFR. Table 1 shows an example of such a study.

Typically, a 40% increase in MFR from pellets to parts is considered as an upper limit for an allowable change in average molecular weight. Processors traditionally only had to be concerned about the effect that their molding process had on this parameter. But as the results show, gamma and electron-beam sterilization can account for more than half of this allowable change, which places much greater constraints on the molding process.

Some material suppliers have suggested that keeping the molded parts dry until sterilization is performed may prevent some of this shift. However, studies have shown that the moisture content of the part during sterilization has no statistically significant effect on the MFR of the parts after sterilization. And even if this were a viable solution, it would place significant and unwelcome constraints on the device manufacturing and assembly process.

Stressed about overcrowding?
Another concern has arisen as our experience with the sterilization processes has increased. Some limited work on PC parts before and after sterilization indicates that both gamma and electron-beam sterilization increase the level of internal stress in the part. This has been measured using thermomechanical analysis (TMA).

Figure 3 shows plots of dimensional change as a function of temperature for an as-molded PC component and the same component after gamma and electron-beam sterilization. Stresses locked in the part can be measured in a relative manner by monitoring the coefficient of expansion as the polymer approaches its glass transition. The glass transition represents the onset of an increased level of molecular motion in the polymer matrix. Amorphous polymers normally soften at this point, ending the expansion process and even producing contraction due to penetration as the modulus of the material declines by more than 99%.

However, one of the key causes of molded-in stress is localized overcrowding at the molecular level. High pressures coupled with rapid cooling create a pressure differential across the molded part, with pressures being highest near the gate and lowest near the end of flow. The larger these differences, the greater the level of stress in the part. At locations near the gate, the polymer chains in a highly stressed part are compressed more tightly than they would be at equilibrium.

Reaching the glass transition temperature allows for a relaxation of this overcrowding. This results in the rapid expansion seen in Figure 3 at temperatures greater than 140°C. The results show that there is some level of molded-in stress in all three samples.
However, the magnitude of the expansion increases with sterilization, reaching its highest level with the use of electron beam. This is another example of an effect that is likely to have very little influence on short-term performance, but may appear as a reduction in mean-time-to-failure when the product is under constant external stresses or is in the presence of aggressive chemical environments.

Finally, there has been a tendency to treat all radiation sterilization processes as equivalent in terms of their effect on the mechanical properties of polymers. However, one recent study using radiation-resistant PP has already shown important differences. Increases in MFR were observed to be greater using gamma than electron beam. While these differences did not result in a disparity in the functional performance of newly sterilized parts, product subjected to accelerated aging showed a divergence in performance along with a continued increase in MFR. The increases in MFR occurred more rapidly in gamma-sterilized parts, and ultimately the differences in response to aging resulted in parts passing qualification when sterilized by electron beam but failing when sterilized by gamma.

The bottom line is that we continue to look for guidance in studies that were done in a much simpler time. These studies formed the foundation for the work going forward, and they provided some good guidelines. But our experience with real-world products is showing a need for more careful and thorough evaluations. In general, the trends point toward a need for less optimism and more care in understanding the interaction between design, material selection, processing, and product performance when high-energy radiation sterilization is involved.