The sterilisation of medical devices and their packaging is critical as the presence of a single microorganism on an instrument could have dire ramifications. Maetrics’ sterile products specialist Tracy Rennison debates the pros and cons of the various methods available.
Sterilisation has been around for centuries – from the Egyptians’ employment of pitch or tar in the embalming process to the 19th-century works of Lister, Pasteur, Tyndall and Koch, who pioneered the use of antiseptic solutions and heat as a sterilising agent, and through to the present day. More recently, Spaulding and Rutala devised their respective classification systems for the disinfection of instruments based on the criticality (the degree of risk of infection) of their intended use and the characteristics of an ideal sterilisation method.
Sterilisation is the process of killing all viable microorganisms, including resistant spores, to a high level of probability, ensuring that the likelihood of a microorganism’s survival is no more than one in a million.
A number of different techniques are employed to achieve the goal of medical device sterilisation, which are based on the type of energy source and microorganism destruction method (see tables 1 and 3).
Determining the right sterilisation method for a particular medical device can be a daunting proposition: if the incorrect method is selected, the consequences for the device, patient and time to market can be catastrophic.
Sterilisation techniques have been used to sterilise medical devices for more than 100 years. The first method ever used was heat, primarily steam sterilisation.
Steam is one of the oldest methods of commercial sterilisation. It employs pressurised steam to generate temperatures of 121°C for 15 minutes, for liquid sterilisation, and of 134°C for three minutes, for porous load sterilisation.
Steam sterilisation is widely used in a hospital or dental setting to treat reusable surgical or dental instruments. Steam sterilisation of a particular medical device is dictated by the temperature suitability of the components and the porosity of the sterile barrier packaging. This method is not suitable for plastic materials, for instance, which deform at high temperatures, but those that are polypropylene based will withstand steam sterilisation.
In line with the development of combination medical devices, which incorporate a biological or medicinal component, a new type of steam disinfection has been designed to sterilise gel-filled plastic containers that would otherwise be too dense and impenetrable for alternative methods. This mode is called air-ballasted steam. Air is injected into the chamber during the sterilisation phase to ensure that the plastic containers do not implode.
Another heat-based technique is dry heat sterilisation; however, this is not widely used to sterilise medical devices as it involves the processing of instruments at very high temperatures over a long period of time – typically at 160°C for two hours – to ensure a device is entirely sterile. Dry heat is more suitable for heat-resistant products such as metal devices or powders.
Radiation sterilisation relies on the ionising properties of certain rays to elicit an antimicrobial effect. Three rays are typically used: beta rays in an electron beam, gamma rays (usually from 60Co) and X-rays. X-rays are most penetrating; beta rays are least.
Radiation sterilisation is suitable for complex medical devices that incorporate heat-sensitive plastic components. The benefits of radiation technologies are that they generate no toxic by-products and do not require porous packaging, so foil or transparent packaging can be used to produce aesthetically pleasing effects.
Gamma is the most widely used radiation technology as it combines good penetration, which ensures the sterilisation of a wide variety of medical devices, with differing densities, and has the ability to construct and operate a safe facility. Gamma is primarily chosen as it can disinfect plastic components and other heat-sensitive materials with a typical sterilisation dose of 25kGy, and has a proven history.
Devices with complex pathways and lumens are suitable for gamma sterilisation as the rays will penetrate all materials. The denser the material, however, the more difficult it is to achieve penetration. For instance, large or bulky metal instruments will require added controls to ensure effective sterilisation, and not all plastics are compatible with gamma – some become discoloured or brittle after processing; the reaction is dose-dependent (see table 2 for common plastic formations’ stability under radiation).
Electron beam radiation technology generates an electron shower by accelerating electrons through an evacuation tube and focusing them into a beam using magnets. The product is passed through the beam for sterilisation. Primarily high-energy electron beam processing is used, typically at 10MeV, to ensure sufficient penetration of electrons. Electron penetration is proportional to the energy and inversely proportional to the product density.
Electron beam sterilisation is employed to disinfect medical devices that contain radiation-sensitive materials with complex geometry. Due to the beam’s reduced penetration, however, the product’s density must be uniform throughout; for example, electron beam would not be suitable for metal implants because of the density changes within the shippers. As electron beam processing operates within a lower dose range than gamma, there is less damage to plastic components. To aid penetration, the instrument can be sterilised in a rack to correctly orientate it.
X-ray sterilisation technology is currently the least used radiation technology. Gamma and electron beam sterilisation are optimised for bulk continuous sterilisation, where the throughput and sterilisation time must be as short as possible. High-energy X-ray technology has some safety implications when optimised in this bulk processing format due to the extra shielding required.
With the advent of new technologies and equipment, there is set to be a shift away from bulk sterilisation in a pallet configuration format towards in-line sterilisation at the point of manufacture. In-line sterilisation, such as low-energy X-ray machines, offer distinct advantages including decreased lead times, increased flexibility in the sterilisation dose delivered and more effective process control, as each sterilisation batch comprises just one item. Other key benefits will be the reduction in transportation costs, lead time to market, and the need for segregation of sterile and non-sterile products.
The third sterilisation method used is chemical sterilisation. This is primarily achieved in the medical device industry through the use of ethylene oxide gas.
Ethylene oxide is used to treat heat-sensitive products, those that are degradable by radiation methods, and complex devices or kits with long lumens. Ethylene oxide is a toxic molecule, however. Due to its carcinogenic and explosive properties – which require the employment of special health, safety and emissions controls to ensure its safe use – ethylene oxide sterilisation is generally performed by third-party contract sterilisers.
Ethylene oxide sterilisation involves three main stages: preconditioning (to warm and humidify the load), sterilisation (where the ethylene oxide is injected and held for the required length of time) and degas (where heat is used to drive the ethylene oxide and by-products from the devices).
Ethylene oxide is one of the most versatile sterilisation methodologies as there are a number of variables that can be controlled and altered to derive a highly efficient bespoke cycle, sterilising a wide range of extremely complex medical devices.
Considerations involved in this type of sterilisation stem from the device’s complexity, where the ability to drive the gas into and out of the packaging and product is paramount to heat and radiation-sensitive components. Care must be taken with electronic components and devices containing batteries as the moisture may affect circuitry, and batteries may present an explosion risk.
Gas plasma sterilisation was developed in the 1980s as an alternative to ethylene oxide. It is suitable for temperature-sensitive materials as it can take place at lower temperatures, but is not recommended for products that have long lumens because gas penetration can be an issue.
The use of gas plasma sterilisation is dependent on access to the machines – chamber size is small and so throughput is limited – and porous materials are also unfit for this method as they absorb the hydrogen peroxide before it is generated into the active plasma form.
Physical filtration sterilisation
Filtration sterilisation, also known as aseptic processing, is achieved by filtering the liquid through a tiny pore filter that is small enough to remove vegetative microbial cells and spores. Sterilisation occurs before final packaging, necessitating a high level of air cleanliness to ensure that the sterile liquid is not contaminated. Aseptic filling is typically completed in an ISO class 5 – or better – clean room environment.
Filtration sterilisation is selected for devices that are not suited to usual sterilisation methods. It’s mainly used to sterilise liquids as their chemical structure and activity would be denatured or destroyed by conventional modes. As technology and science continue to advance, and combination medical devices incorporating medicinally or biologically derived products have been developed, filtration has become the only suitable method of disinfection for some products.
There are a number of effective sterilisation methods for medical devices. Selecting the most appropriate one depends on a number of factors, such as complexity of device design, geometric complexity and the use of novel active components. Secondary considerations include lead times to market and validation requirements to satisfy the industry’s regulatory bodies.