A critical stage in the production of medical devices is when they need to be sterilised before distribution. Any slip-ups in this process could have severe consequences for the patient if they are infected by a contaminated instrument.

There are numerous factors to consider when selecting a method of sterilisation to be used, which make it a complicated decision to make. A report from the Gamma Industry Processing Alliance says, “The choice for any given irradiator location is a technological and site-specific choice very much dictated by infrastructure (space, utilities, transportation, access) availability, the physical and technical resources available (skilled labour and repair capability), the type and volumes of products to be sterilised, the ability to maintain a reliable throughput of product to be sterilised and the needs of the marketplace.”

Irradiation has been used since the 1960s to sterilise single-use medical devices as an alternative to the heat or chemical-sterilisation processes. Irradiation technologies are well established and are used to sterilise approximately 45% of the global market for single-use medical products, according to the International Irradiation Association (IIA).

Gamma irradiation has tended to be the method of choice and comprises approximately 90% of the sterilisation market, according to the IIA. There are a number of advantages to the method, such as the high processing speeds and low costs. It also allows the operator to predict the amount the bioburden, which cannot be done with any other technique.

An appreciation of the advantages of gamma is shared by a number of experts in the field. “Compared with electron-beam (E-beam) processing, gamma irradiation has good penetration power,” says Sean Hanley, sterilisation senior fellow at Boston Scientific. “Therefore, it will penetrate full pallets of product, which makes it suitable for medium-large scale volumes of product. Processing times are good, typically four to six hours.”

As easy as alpha, beta, gamma

As gamma irradiation is a well-established technique, there is also a ‘good geographical spread’ of suppliers. However, there are problems with the method, such as its incompatibility with some materials, and the relatively low level of public awareness and acceptance of its use.

In addition, gamma irradiation cannot be used universally. “It is not suitable for all materials,” says Hanley. “Some types of plastics and polymers, drugs and biologics may be impacted at high doses, and packaging material may discolour, due to the processing.”

“It is hard to point out a technology that works for everything. The product characteristics and applications, the nature of the bioburden and the product all need to be considered when selecting the most suitable sterilising technique.”
Sean Hanley

One of the biggest issues with the use of gamma is the radioactivity. “Gamma irradiation, due to the radioactive isotope, presents a hazard that needs to be considered by the sterilisation facility,” Hanley explains. “It typically requires a quarterly validation activity – a quarterly dose audit. This adds a bit to the overall validation burden.”

Although gamma irradiation is the most commonly used approach, there are a number of alternatives, such as E-beam, heat treatment and plasma. However, it isn’t straightforward to determine which of these is best. It is also important to note that not all devices can be sterilised effectively using any method.

“It is hard to point out a technology that works for everything,” says Hanley. “The product characteristics and applications, the nature of the bioburden and the product all need to be considered when selecting the most suitable sterilising technique.”

Ethylene oxide (EO) is a relatively cheap sterilisation option and its ability to sterilise up to 24 pallets at a time mean it is well suited to large-scale production. It is also compatible with the majority of materials, making it a relatively versatile approach.

However, it has several disadvantages.“EO is getting a lot of negative press for environmental reasons,” says Hanley. “Companies are being encouraged to find alternative methods or reduce EO gas usage.”

“Although some new technologies are available, it is unlikely that they will be operated at an industrial scale or meet the demand. The compatibility may be an issue and converting from one technology to another is not often the preferred choice of the medical device industry.”
Gustavo Varca

In addition, EO sterilisation tends to take longer than gamma irradiation, with processes varying 18–76 hours. There is also an issue with residual EO gas remaining on the devices.

As with gamma irradiation, the environmental impact of EO is problematic. “There have been recent Environmental Protection Agency concerns over EO gas,” says Gustavo Varca, scientific adviser at the IIA. “Changing sterilisation methods is not easy because product design testing needs to be reconsidered and the regulatory burdens are significant.”

The products requiring sterilisation are also everchanging, introducing new challenges to be navigated by the industry. Growing complexity in products, and the increasing use of nanotechnologies and biologics, has meant that the industry is increasingly engaging with research institutes and universities that are undertaking groundbreaking research.

Old tricks

As a result, some methods more commonly used in the past are making a return, such as the use of X-ray and nitrogen dioxide. Although this increases the options available, these methods do not have broad compatibility, which decreases their usefulness.

“Gamma and EO will remain the dominant methods,” says Hanley. “Novel methods such as gap plasma, hydrogen peroxide, ozone and chlorine dioxide are gaining some interest for complex medical devices.”

Hanley predicts that some new medical devices that contain drugs and biologics may not be compatible with gamma irradiation and EO gas sterilisation, so new alternatives will be required.

Some of the newer sterilisation methods that have not yet been widely implemented may be given more serious consideration. Examples of this include lowmid voltage electron beams, particularly for low-tomedium- density products, and X-ray technology that has the same penetration qualities as gamma radiation.

However, Varca does not foresee any major changes occurring. “For sure, one thing is immutable – the need for sterilisation,” she says. “Although some new technologies are available, it is unlikely that they will be operated at an industrial scale or meet the demand. The compatibility may be an issue and converting from one technology to another is not often the preferred choice of the medical device industry.”

The picture is different with regard to reusable devices. Sterilisation for these is likely to remain on a small scale, using techniques such as autoclaving, which is one of the most commonly used.

Similarly to other methods, there are limiting factors, which can compromise the levels of sterilisation achieved by autoclaving. For example, sterilisation has to be performed outside of the package, which can make it more difficult to ensure the device in question is actually sterile.

It is also important to note that some products cannot be sterilised at all. “It is relevant to highlight that most of the medical devices available cannot should not be reused,” says Varca. “I know it sounds ‘ungreen’, but there is a scientific basis for that.”

Radiation sterilisation of medical devices

In the 1950s, the replacement of reusable devices by single-use devices was made possible by the availability of affordable polymers. As these new materials could not withstand the high temperatures of traditional heat sterilisation, it was necessary to use a ‘cold’ processes. Gamma irradiation using a cobalt-60 source provided the required penetration and characteristics, and became a leading sterilisation modality. Today, electron beam and X-ray technologies offer alternatives, but to date these technologies are not widely used to sterilise medical devices.

Over the years, the concept of sterility evolved from absence of any viable microorganism, an absolute condition, to the probabilistic notion of sterility assurance level (SAL) – the presence of one surviving microorganism in a population of items. Indeed, the inactivation of a population of microorganisms follows an exponential pattern and there is always a finite probability of a microorganism surviving sterilisation, regardless of the extent of processing applied. An SAL of 10–6 indicates a probability of one item being contaminated in one million. This is still the most widely used value, though some devices could certainly be sterilised at less-drastic SAL values without added risk for the patient. As medical devices have become more complex it has become difficult to achieve an SAL of 10–6 without damaging the device. In such situations a reduced SAL would enable complex devices that include biological components to be more effectively sterilised.

An essential element in the design of a radiation sterilisation process is the determination of the minimum dose necessary to obtain the required SAL. The Association for the Advancement of Medical Instrumentation developed a variety of methods for this purpose and to periodically ensure that this dose remains effective (dose audits). As the tolerance of polymers to irradiation varies, it is also necessary to determine the maximum dose that can be used without affecting the quality or functional properties of the device, considering that irradiation is not delivered homogeneously but leads to gradients of doses within the treated product. When a radiation sterilisation process has been properly validated, the release of sterilised items in routine is essentially based on the verification of the doses that were delivered. It is not necessary to test treated samples for sterility or to use biological indicators to assess efficacy.

Source: International Irradiation Association