Mike Eaton, UK marketing manager, Isotron, offers a comparison of the available technologies for the sterilisation of single-use medical devices and cleanroom consumables.
For a manufacturer of sterile cleanroom consumables or single-use medical devices, understanding the key differences between the sterilisation technologies can have a huge advantage in terms of both speed of processing and limiting the detrimental effects of the process. This article explores the advantages and cautions presented by gamma, electron beam and ethylene oxide sterilisation technologies.
Many items introduced into cleanrooms, such as packaging and raw materials, are routinely sterilised prior to use, to ensure they have low bioburden and do not contaminate the cleanroom or the product being manufactured in the cleanroom. Medical devices sold as sterile must meet the requirements of EN 5561 Sterilisation of medical devices — Requirements for medical devices to be designated sterile. This is related to the demonstration of a Sterility Assurance Level (SAL) of 10-6.
There are three main technologies available to the medical device and consumable manufacturers:
Gamma
The radioisotope cobalt 60 has been used for more than 40 years as the predominant source of radiation in gamma plants. This isotope is manufactured from naturally occurring cobalt (cobalt 59) using a process of neutron bombardment over a number of years. The radioactive source, cobalt 60, obtained from this process is then encapsulated in multiple layer stainless steel rods (pencils), which in turn are housed in a three dimensional array called a source rack.
The sterilisation process involves loading product, typically in its final packaged format, onto pallets or aluminium containers (totes) outside of the cell; these are then transported into the plant and around the source via the conveyor systems. Once inside, the product passes around the source rack in a carefully defined, pre-determined fashion to deliver the intended dose. It is important to note that the product does not become radioactive during or after processing.
The mode of lethality is via ionisation of molecules within and around the organism, which produce reactive electrons and free radicals. These species attack cellular constituents causing damage to the DNA and critical proteins, preventing replication or killing the micro-organism.
Electron beam
This technology employs sophisticated acceleration systems to generate high-energy beams of electrons. The electrons are then scanned back and forth at frequencies of 50–100Hz to produce a curtain of electrons through which the product then passes. As with gamma, the product is loaded onto conveyor systems outside of the cell and unloaded after the process has been completed. A principal difference between gamma and electron beam systems is the dose rate, which is significantly higher in electron beam plants. Consequently, cycle times are shorter, which can sometimes reduce the adverse impact of radiation on some materials, particularly where these effects are associated with oxidative changes.
The drawback, however, is that the penetration of electrons is relatively poor compared with gamma photons, which means this technology is favoured for low density products and in carefully controlled packaging configurations.
The mode of lethality is the same as gamma via ionisation of molecules within and around the micro-organism.
Ethylene oxide
Ethylene oxide (EtO) has been used for many years for the sterilisation of raw materials, packaging and single-use medical devices. One of its key benefits is its broad material compatibility, so it is frequently the method of choice when dealing with polymers that are not compatible with radiation process (e.g. items containing PTFE).
Typically the ethylene oxide process handles batch volumes of between 20 and 90m3 in specially designed and automated sterilisation chambers. The process takes between 12 and 24 hrs, including pre-conditioning, with a further 12 hrs to five days needed to remove residuals from the product.
The process is controlled by monitoring of process parameters but also by the testing of biological indicators (preparations of Bacillus atrophaeus spores). As these biological indicators (BI) can take between three to seven days to test, the typical turnaround time for ethylene oxide is around seven days. Pressure to reduce this time has led to the development of ‘rapid BI systems’ capable of delivering results within hours, and of parametric release systems that, although not in general application, are becoming more frequently applied.
The mode of lethality is alkylations and/or oxidative reactions involving sulphydryl, amino, hydroxyl and carboxyl groups of proteins and imino groups of nucleic acids as well as cellular proteins.
Each process has its advantages and disadvantages:
Processing time
A shorter processing time and significant flexibility gives e-beam the advantage over both gamma and ethylene oxide. An electron beam process takes minutes compared with 8 hrs (average) for gamma and 24 hrs for ethylene oxide (minimum). Furthermore, the electron beam process offers significant flexibility and the scope to offer rapid turnaround service (same day).
Both electron beam and gamma processes are released against dosimeter results, which can be read immediately following processing. Providing the dosimeters are within specification and the products processed without deviation, the batch can be certified and returned, offering a very rapid release process.
In contrast the ethylene oxide process requires the growth of biological indicators, so release is often limited to 3–7 days following processing. Parametric release offers immediate release providing all the parameters are within specification.
Compatibility
Products processed using electron beam require less exposure time within the irradiation cell. This results in less ionisation of air (generating ozone) and less oxidation of the polymers. Therefore, for some polymers electron beam offers lower levels of degradation than a corresponding radiation dose with gamma. However, many of the polymers commonly used offer resistance to oxidation, exhibiting equal performance for both gamma and electron beam.
Since the irradiation process imparts energy, temperature effects need to be considered. The gamma process is slow in comparison with the electron beam, which allows the heat imparted during the process to dissipate naturally with only minimal temperature rises. In contrast the electron beam delivers its dose very quickly and therefore a rapid temperature increase occurs at a macro level. At normal processing conditions this temperature rise can be in the order of 20°C above ambient. Although this rapid heating effect has minimal effect on most polymers this should be considered and evaluated during product trials.
Providing a product is packaged with a breathable membrane, ethylene oxide gas is suitable for almost every polymer. However, the mode of kill is via surface contact (surface sterilant) and therefore is not suitable for products containing liquids.
Penetration
Ethylene oxide gas displays a high degree of penetration into most materials provided that the product is packaged using a breathable material, such as Tyvek.
Gamma radiation displays a high degree of penetration into most materials, with the rate of penetration being dependent on density. Typical dose ranges are 25–40kGy; however, these can be significantly reduced on low density products.
Electron beam processing is suited only to densities below 0.2g/cm3. This excludes the majority of powders, liquids and metals. Typical dose ranges are 25–70kGy. The dose distribution within a product is complicated, resulting in extensive validation with typically 10 times the number of dosimeters used compared with gamma.
Residuals
The amount of residual ethylene oxide remaining on product after processing is dictated by product design, materials and the sterilisation process. The limits for residual levels are referenced in ISO 10993-7.2
There are three residuals to be considered: ethylene oxide; ethylene chlorohydrin (ECH) and ethlylene glycol (EG). The limits for the US and Europe are expressed as Mg/device and for Japan as PPM. The limits are set by taking into account the length of time the product resides in the body. Residual levels are lowered during the aeration phase of the process.
Neither gamma nor electron beam produces residuals.
The process parameters for the three processes are set out for easy comparison in Table 1.
In conclusion, it can be seen that there is a wide range of technologies available for the sterilisation or decontamination of items entering the cleanroom and for microbiological control of the cleanroom environment. The choice of technology will depend to a large extent on volume of product, turnaround time requirements and the type and composition of the product to be sterilised.
Certain technologies will offer benefits over others, depending on the needs of the customer and product components. It is strongly recommended that the manufacturer discusses the product and processing requirements with the contract steriliser before deciding on a technology and performs a number of trials to establish whether the process causes any deleterious effects to the product or packaging and develops a processing specification based on the results of these trials.
Isotron offers all technologies in the UK, together with supporting laboratory services. In June 2009, the company opened a new 10MeV electron beam plant in Tullamore in Ireland and an ethylene oxide facility in Suzho in China. In total, the company now has 19 processing sites in nine countries.
Contact
Mark Eaton UK marketing manager Isotron Synergy Health plc Ground Floor Stella Windmill Hill Business Park Whitehill Way Swindon SN5 6NX UK T +44 1772 299900 www.isotron.com
