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Alternative method for sterilisation: X-rays

By Tim Sandle - Ph.D. 

 

There are several emerging methods of sterilisation which may, in time, become established methods for the sterilisation of pharmaceutical products, medical devices or healthcare materials. Such technologies include: X-rays, ultrasonication, supercritical gases, ultraviolet light, pulsed light, microwaves, infrared radiation, and plasma. This article considers X-rays.

All emerging technologies need to meet certain criteria in order to be considered as suitable methods for the sterilisation of a product.

These criteria are(1): 

  • The technology can achieve a Sterility Assurance Level of 10-6 or greater.
  • The product can withstand the sterilisation conditions.
  • The process can achieve the necessary assurance of sterility.
  • Terminal sterilisation of the product can be achieved within the final packaging.
  • No chemical residues are created as a by-product of sterilisation.
  • Understanding the physical and chemical conditions required to achieve sterilisation.

In addition, novel sterilisation technologies:

  • Need to be sufficiently advanced to be used on a practical scale.
  • Must be able to be validated, to show microbial kill.
  • Must be affordable.
  • Must be safe to use.
  • Need to have a processing time that meets with production requirements.

To assist with the introduction of new technologies, the international standard ISO 14937 ‘Sterilisation of health care products -- General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilisation process for medical devices’(2), provides useful guidance for the development and validation of alternative technologies. The approach is also useful when approaching the sterilisation of other items.

X-ray technology

X-radiation (composed of X-rays) is a form of electromagnetic radiation, where X-rays originate from transitions in the electrons from an atom. X-rays have a wavelength in the range of 0.01 to 10 nanometres, corresponding to frequencies in the range 30 petahertz to 30 exahertz (3×1016 Hz to 3×1019 Hz) and energies in the range energy of 5 to 7.5 MeV (million electron volts). X-rays are shorter in wavelength compared with ultraviolet rays and they are longer than gamma rays. X-rays are sometimes referred to as Röntgen radiation(3). X-rays have strong penetration capabilities because, like gamma, X-rays consist of photons and react with the material being processed in a similar manner(4). The requirements for using X-rays for the purposes of sterilisation are set out in the standard ISO 11137-2:2017(5).

 W.C. Röntgen

 

X-ray irradiators

Facilities offering X-ray sterilisation are termed X-ray irradiators, which are electrically powered (similar to e-beam). X-rays can be generated by an X-ray tube, and the process has similarities to an electron beam accelerator (e-beam sterilisation). This is a vacuum tube that uses a high voltage to accelerate the electrons released by a hot cathode to a high velocity. The high velocity electrons collide with a metal target, the anode, creating the X-rays. The use of a machine (called a ‘converter’ or a ‘generator’) makes the application of X-ray sterilisation similar to electron beam method (and unlike the passive gamma radiation process, which uses an Cobalt-60 isotope). In terms of the treatment of items, X-rays either permit the conveyance type approach where product passes continuously through the beam, as used with e-beam sterilisation; or, the multi-pass approach, with items placed in totes (often formed of thin sheets of tantalum), used with gamma radiation processes. Typically two passes through the X-rays is required to achieve a 6-log sterilisation. Compared with both e-beam and gamma, the penetration achieved by X-rays is often greater.

The amount of radiation dose from an X-ray generator received by the product is a function of the design of the irradiator, the power of the accelerator, the energy of the electrons, the width of the region scanned by the electrons, the design and conversion efficiency of the x-ray target, the density and thickness of the product as it is presented to the beam and the speed of the conveyor.

The concept of using X-rays to decontaminate is not new, the process has been used in food processing for many years. However, here the objective is to reduce contamination down to an acceptably low level and to use lower energy levels (below 5 MeV) due to the potential for higher levels to impart radioactivity to foods for human consumption. 

The application of X-ray technology for sterilisation is similar to other radiation based sterilisation measures. This means that X-ray installations, like gamma radiation, are typically designed to sterilise products in their final shipping configuration primarily because of their deep penetration capabilities. The materials being subject to this form of sterilisation need to be sufficiently robust. In addition, the material must be capable of converting electron energy into bremsstrahlung radiation (the term applied to electromagnetic radiation produced by the deceleration of a charged particle when the particle is deflected by another charged particle. For example, the deflection of an electron by an atomic nucleus). The creation of electromagnetic energy (photons) is with an energy in the same range as gamma. The method of assessment of the sterilisation process is similar to gamma and e-beam in that dosimeters are used(6).

 

Microbial kill

X-rays have the same basic effect on microbial cells as gamma rays and electron beams(7). This is due to the interaction of radiation with cellular DNA (which causes depolymerisation) and the physical and biochemical effects of the radiation on other cell structures such as RNA, proteins, cell membranes and enzymes(8).

The effectiveness of microbial kill at 5-7 MeV has been shown with studies using the spore-forming bacterium Bacillus pumilus(9). This organism demonstrates high resistance to environmental stresses, including UV light exposure, radiation, desiccation, and the presence of oxidizers. A second organism against which X-ray effectiveness can be assessed is Deinococcus radiodurans, which is very resistant to ionizing radiation, ultraviolet light, desiccation, and oxidizing and electrophilic agents. This is due to the bacterium having multiple copies of its genome and rapid DNA repair mechanisms. The resistance of D. radiodurans to radiation is up to 25 times more than the resistance exhibited by Escherichia coli(10). Biological challenges can help with the development of new cycles; however, the use of dosimetry, supported by product bioburden testing intervals, is more common for assessing routine sterilisation operations.

 

Advantages and disadvantages

The advantages of X-ray sterilisation are the fast times, uniform treatment of products (what is known as the Dose Uniformity Ratio), and a flexible operational approach that enables different products with different dose requirements in the same irradiation cycle. Generally, a lower dose can be provided to a product compared with gamma. The lower dose can help to minimise the impact of material degradation. This is especially so with polymeric materials where X-rays are gentler than gamma irradiation(11). The higher penetration achieved by X-rays also allows for larger packaging configurations to be used compared with gamma radiation processes. In addition, there are no air emissions or residual waste products with X-ray technology (unlike the residuals associated with ethylene oxide sterilisation) (12).

Despite the long history of X-ray applications in medicine and industry (especially for diagnostic imaging), their application for medical device and healthcare products sterilisation remains less advanced. The use of X-rays for sterilisation has been limited due to the high expenditure associated with the under-developed application of the technology. Another reason relates to the need to factor in a more detailed conversion setting for different materials, making the preparation step lengthier compared with gamma radiation. However, introduction of high-power, reliable accelerators and the economics of large X-ray sterilisation facilities are starting to become comparable with similar capacity gamma sterilisation facilities.

 

Transitioning from gamma to X-ray

When the transition from the more established gamma radiation process to X-rays is being considered, the following factors need to be taken into account:

  • Identify specific polymers/elastomers used in medical products that present the greatest data gaps for radiation effects and would be of greatest industry impact if transitioned to X-rays.
  • Measure any physical effects that these materials exhibit when they are given sterilisation-level radiation doses from X-rays (such as the use of the ‘yellowness index’ for plastics).
  • Determine whether these effects would preclude the use of X-ray for associated medical products.

 

Conclusion

Compared with gamma, X-rays used for sterilisation have the highest potential penetration depth in a product. This advantage is off-set by the few number of X-ray generators available and less product validation or compatibility data being available. While the decontamination of products and materials with high-energy X-rays was developed during the 1970s, the first application of the technology for sterilisation (medical devices) did not begin until the early-2000s. The lower take-up may be about to change since interest in X-rays for sterilisation has increased in the 2020s following advances with higher beam power ratings of industrial electron accelerators. Along with e-beam and gamma radiation, three related-yet-different technologies are available.


References

  1. Dewhurst, E. and Hoxey, E. (2003). New and Emerging Sterilisation Technologies. In Hodges, N. and Hanlon, G. Industrial Pharmaceutical Microbiology, Euromed: Basingstoke, 14.1-14.21
  2. ISO (2009). International Standards Organization. ISO 14937:2009. Sterilisation of health care products -- General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilisation process for medical devices, ISO: Geneva
  3. Novelline, R. (1997). Squire's Fundamentals of Radiology, 5th edition, Harvard University Press: Harvard
  4. del Regato, J.A. (1985). Radiological Physicists, American Institute of Physics: New York
  5. ISO 11137-3:2017 Sterilization of health care products — Radiation — Part 3: Guidance on dosimetric aspects of development, validation and routine control, ISO: Geneva
  6. Fairand, B. (2001) Radiation Sterilization for Health Care Products: X-Ray, Gamma, and Electron Beam, CRC Press, Florida, USA
  7. Ginoza, W. (1967). The effects of ionizing radiation on nucleic acids of bacteriophages and bacterial cells. Annual Reviews of Nuclear Science, 17, 469 – 512
  8. Morrissey, R.F. (2002). Radiation sterilisation: past, present, and future, Radiation Physics and Chemistry 63 (3-6): 217-221
  9. Tallentire, A. and Miller, A. (2015) Microbicidal effectiveness of X-rays used for sterilization purposes, Radiation Physics and Chemistry, 107: 128-130
  10. Brooks B W, Murray R G E, et al. (1980) Red-pigmented micro cocci: a basis for taxonomy. Int J Sys Bacteriol. 30:627–646
  11. Meissner, J., Abs, M., Cleland, M., et al A (2000) X-Ray Treatment at 5 MeV and Above, Radiation Physics and Chemistry, 57 (3-6): 647-651
  12. Meissner, J. (2008) X-ray sterilisation, Med Device Technol. 19(2):12-4.