The demand for medical devices keeps growing and so does the demand for sterilization, making all available sterilization options necessary. Most single use medical devices are made of polymers that withstand only a moderate temperature increase. For decades now, ethylene oxide and gamma radiation have been the dominant ’cold’ sterilization methods. Concerns on the future availability of these methods, whether justified or not, and the potential consequences on global sterilization capacity, have rekindled the interest in alternative technologies. Irradiation by electron beam and X-ray is among them.
Electron accelerators have been used in different industries since the 1950s, mostly to modify polymers, e.g., cross-linking of polyethylene for cable insulators. The use of electron beams to sterilize medical devices developed from the 1970s. Many major medical device manufacturers have now adopted electron beam accelerators as an in-house sterilization solution while the offer for contract electron beam irradiation also grew. In 2011, the first high-power X-ray sterilization facility - now owned by STERIS- started operation in Switzerland. Since 2020, the number of new EB-X service facilities coming into operation is greater than the number of new gamma facilities. New X-ray capacity has been or is being built in the USA (near Dallas, TX, Northborough, MA, Libertyville, IL), Germany, the Netherlands (Venlo) and Thailand (Chonburi).
Accelerators have various advantages of over cobalt-60 as a source of ionizing radiation:
- They are durable electric machines that can be sourced from many suppliers.
- The emission of ionizing radiation can be paused.
- Their safety and security characteristics make licensing and regulatory compliance easier.
But unlike gamma irradiators
- They are complex machines requiring a significant spare part budget and technical expertise, which is often addressed through a maintenance contract.
- Full capacity is available from the first day and adjustment to market demand is only through utilization time. When the machine is idle, no electricity is consumed.
Accelerators impart increasing levels of kinetic energy to electrons that emerge from the machine in the form of a beam scanning the product travelling at a controlled speed to adjust the dose. How the electrons are accelerated and how products are exposed relative to the beam characterize the different types of machines. Beyond the many technicalities, for the user, a key factor is ultimately how much energy is required by the machine to obtain the required dose in the product, with the required dose distribution.
The two main characteristics of accelerators are the energy of the beam and power.
The energy is expressed in megaelectron-volts (MeV) or kiloelectron-volts (keV), an electron-volt being an energy unit that can be converted into Joules. Energy determines how far into the product the beam can penetrate. This in turn determines how inhomogeneous the treatment will be, which is quantified by the ratio of the maximum dose over the minimum dose (Dose Uniformity Ratio or DUR). Consequently, energy is a key factor of process capability in terms of the type and density of product and packaging that can be treated. As a rule, the higher the energy, the larger the machine, the larger the footprint, the larger the shielding, and the higher the investment costs.
For a specific energy and target product, the throughput of an accelerator is proportional to its power, expressed in kilowatts (kW). The more power a system has, the less time it takes to deliver a specific dose. Selecting the correct power is a critical decision that must be based on a forecast of the required processing capacity over several years.
Electron accelerators can be used to produce two types of ionizing radiation: electron beams and X-rays. X-rays are produced when a beam electron meets a metal target placed between the beam emerging from the accelerator and the product. Most of the incident electrons power is dissipated as heat and only a small portion is transformed into X-ray, which explains why X-rays were not a commercially viable option for medical device sterilization before the advent of very high-power, medium and high-energy accelerators. Energy yield (kilograys into the product per consumed unit of electricity power) clearly makes electron beams a more efficient technology than X-rays, but this must be balanced against the broad product treatment range and flexibility that X-rays offer.
Electrons or X-rays? Or both?
Processing times are very short with electron beams. The sterilization dose is delivered in seconds compared to several hours for gamma irradiation. The implication is that throughputs can be very large with high-power electron beam accelerators. An additional benefit of high dose rates is that the time available for material oxidation is extremely short, which can minimize the detrimental effects on some polymers.
The main limitation of accelerated electrons is their poor penetration in products relative to photons from gamma or X-rays because they have a mass and a negative electric charge. However, as energies up to 10 MeV can be used, electron beams work well with uniformly packaged products of low and medium density such as gauze, drapes, towels, bandages, wound care dressings, labware, bottles, caps, containers, tubing sets, procedure trays, catheters.
For projects where only surface sterilization is required or if thickness and density are low enough (individual packs), in-line sterilization with low-energy electrons (80-300 keV) or medium energy electrons (up to 5 MeV) produced by self-shielded units is possible. In the pharmaceutical industry, more than 30 units worldwide use electron beams for aseptic filling (1). Tubs containing glass syringes are decontaminated in electron beam tunnels to ensure that the aseptic zone in the filling area remains uncompromised. Recently, a new in-line e-beam sterilization technology using pulsed electron beams has come on the market (2).
Beyond a certain package size or density, treating within the specified dose range with electron beams is not technically feasible. Then X-rays is the radiation sterilization alternative not involving radioactive material. X rays are made of photons that propagate and penetrate much like photons from gamma radiation. Dose distribution is as good and sometimes better than with gamma irradiation, and with shorter processing times. They are penetrating and treat as or even more uniformly as gamma radiation, allowing the treatment of full pallets also.
The choice between electron beam and X-rays will be guided by package size, density, geometry, and the interval between the specified minimum and maximum doses (required DUR).
Dual technology systems (EB and X) are hybrid solutions to accommodate products having different DUR tolerances. The advantage of these dual systems is the flexibility that they offer to treat some products with one technology and the rest with the other. However, they are always optimized for one technology since they are an e-beam system with X-ray capabilities or an X-ray system with e-beam capabilities. This dual system is a compromise adopted where the products to be sterilized are very diverse.
Changing sterilization modality
The regulatory environment in which medical device manufacturers operates tend to make them conservative. Though not necessarily optimal, gamma irradiation is a familiar and simple hence comfortable option, especially for grandfathered products that would be too expensive to revalidate. Considering a conversion requires efforts that can be hindered by the lack of knowledge regarding electron beams and especially X-rays even among regulators. The ISO 11137-1 standard on radiation sterilization governs all three modalities but has been used for gamma radiation much more than for the two other types of ionizing radiation. Over the past three years, various stakeholders have tried to help medical device manufacturers to consider a possible change.
In the USA the “Team Nablo” project, operated by Pacific Northwest National Laboratories (PNNL), has organized an industry collaboration involving major medical device manufacturers to fill knowledge gaps regarding material compatibility with the different types of ionizing radiation (3). In 2020 the Panel on Gamma and Electron Irradiation summarized normative requirements in EN ISO 11137-1 when changing of radiation sterilization modalities, especially from gamma to X-ray (4). The Bio-Process Process Systems Alliance (BPSA) has laid down a testing strategy to enable much of the qualification data already in place for gamma to be leveraged as fully applicable to X-ray (5). The International Irradiation Association (iia) published an accelerator buyer guide to help manufacturers make an investment decision (6). AAMI will publish AAMI TIR 104 entitled Transferring Product between Radiation Sites or Modalities in early 2022.
Recent developments clearly point to a growing importance of accelerator-based electron beam and X-ray sterilization among the available sterilization modalities. This is the result of external factors such as the need for more sterilization capacity, concerns on future of well-established modalities, and therefore the need to risk-manage sterilization capacity. It is also the result of progress and innovation in accelerator technology. The design and components of recent machines have made them more reliable. The offer has considerably expanded and diversified, and though still retaining a degree of complexity, improved interfaces have rendered machines more user-friendly. Many manufacturers have also made their discourse less technical in order to better respond to customers' questions and expectations. The lack of familiarity with X-rays is about to change as major sterilization contractors add X-rays to the range of sterilization technologies that they offer. We are only at the beginning of the growth of accelerators for medical sterilization.
- S. Kleinmann et al.
Effect of Low-Energy E-Beam Irradiation on Presterilized COC Packaging
Pharmaceutical Engineering - Jan. / Feb. 2018
- Christophe MIELOT
Low-energy pulsed electrons: a new in line sterilization modality
Presented at the International Irradiation Association Conference on Recent Developments in Irradiation - October 20, 2021
- Mark Murphy et al.
Transitioning from Cobalt-60 to E-beam or X-ray for Sterilization – A Model for Collaboration
Midwest Medical Device Sterilization Workshop, IARC - September 18, 2019
- Panel on Gamma and Electron Irradiation
"Change of Irradiation Modalities in Radiation Sterilization of Medical Devices– Normative Requirements and Aspects in EN ISO 11137-1" -2020
- Bio-Process Systems Alliance
X-Ray Sterilization of Single-Use Bioprocess Equipment: Part I – Industry Need, Requirements, and Risk Evaluation - 2021
- International Irradiation Association
Accelerators for Sterilization of Medical Devices - A Guide for Prospective Buyers - 2021
- C. Malice and E. Craven
E-beam and X-ray: Why? What? How?
Midwest Medical Device Sterilization Workshop, IARC, September 18, 2019