Toward Enhanced Machine-Based Release in X-ray Sterilization

Abstract

Trends toward the use of irradiator parameter release (also called machine-based release) put pressure on equipment manufacturers to guarantee accuracy and reliability of monitored process parameters. In the specific case of X-ray processing, relevance of these monitored parameters is questionable due to the additional difficulty coming from the fact that the X-ray converter does not have associated parameters or a monitored feedback mechanism. To bridge this gap, this article presents a novel method to verify in real-time consistency of certain X-ray field properties. It covers the description of an X-ray flux monitor and its experimental characterization. The proposed detector can be used as a control and monitoring tool in addition to the conventional “passive” dosimetry per ISO 11137-1 and ISO 11137-3. It can detect photon flux deviation on the order of magnitude of 1%. Its performance would allow real-time monitoring of each pallet being processed and ensure that the correct X-ray beam is directed to the product. Further, the known response of the detector to a product can serve as a validation that the correct product is in front of the beam. Moreover, a detector of this type could contribute to moving from the current dosimetric release to irradiator parameter release. Compared with current practices, benefits would include an increased number of control points used to verify process conformity, real-time information on the radiation field (process output validation), limited manual handling of dosimeters, and verification that the product treated is the same as the performance qualification dose-mapped product.

The use of ionizing radiation for the sterilization of healthcare products and the current practices defined for use of passive radiation dosimetry for monitoring and release of processed product have been reliable and effective for more than five decades. In particular, the use of X-rays was proposed in the 1960s.¹ As with gamma, X-rays are suitable for the processing of thick or dense products due to the penetration abilities of photons. That being said, with the increased use of X-rays for sterilization, the industry has room for improvement.

X-rays are produced by scanning an energetic electron beam on a target. When those electrons interact with matter, part of their energy is converted into electromagnetic radiation (known as bremsstrahlung).² The fraction of electron beam power converted in bremsstrahlung is relatively low but increases with electron energy, and it is greatest for target materials of high atomic number. In our domain of application, the theoretical conversion rate is about 14% at 7 MeV.³ Most of the electron beam energy is deposited in the target, while the remaining fraction is converted into back-scattered electrons. The X-ray converter usually is a sandwich made of three elements (a high-Z material [e.g., tantalum], a cooling channel [e.g., water], and an absorber [e.g., steel]) that absorb the remaining primary electrons, which, unavoidably, also slightly attenuate the X-rays. Its design is very critical, as it directly affects the property of the X-ray beam.

As bremsstrahlung production is a relatively ineffective process, the X-ray irradiator needs to be equipped with a high-power electron accelerator that is able to deliver several hundred kilowatts to produce high-intensity X-ray beams. The availability of such machines did not occur until the 1990s.

X-ray sterilization relies heavily on the consistency and reproducibility of the irradiator facility being able to deliver the stable required electron beam, consistent conversion rate, and shape of the radiation field. The energy, shape (length and width), and intensity of the electron beam are actively monitored and controlled, providing a high degree of confidence in what is being accelerated into the target throughout the entire process. On the other hand, the rate of electron to X-ray conversion and shape of the X-ray radiation field typically is measured passively and often infrequently, typically during annual operational requalification.

Introducing a mechanism to actively monitor the output from the X-ray target can provide immediate feedback, better control, and a greater level of confidence in the delivery and outcome of the sterilization process, enabling machine-based parametric release. Historical experience with machinebased parametric release can be leveraged from the moist heat sterilization industry, where it has been approved and used for several decades.⁴

Materials and Methods

Risks of Nonconformance

To guarantee that the beam is properly irradiating products (i.e., that they are receiving the expected dose), irradiator facilities rely on both proper irradiator performance and qualification processes, such as operational qualification, performance qualification (PQ), and routine monitoring dosimetry.

The proper functioning of the irradiation plant relies on several aspects of the irradiator design, including safety measures to ensure that the risk associated with each failure mode remains at an acceptable level. To continuously guarantee the process output for machine-based sources, the continuous verification of process parameters (e.g., beam current, beam energy, scanning amplitude, beam divergence, conveyor speed) is necessary, as these define the dose.

In the case of an X-ray irradiator, the X-ray converter itself represents a limitation. Although it plays a crucial role in the properties of the X-ray field delivered to the product, any failure of the converter could hardly be detected by machine parameters. For instance, if the beam is misaligned on the X-ray converter, the conversion rate could be altered, thereby affecting the dose in the product.

To illustrate this, Figure 1 shows the result of a Monte Carlo study that simulated the dose delivered in a reference product as a function of the beam misalignment on the X-ray converter.⁵ A beam misalignment of 4 cm could result in a dose reduction of 20%. Although this scenario clearly represents an extreme case, it is not completely unlikely and should be considered by the irradiator operators in their risk analysis. One possible cause for this scenario could be a sudden misalignment of the scanning magnet due to radiation damage of the mechanical structure holding such magnet. Such misalignment obviously would be detected during requalification or during periodic maintenance. However, it would only be detected by routine dosimeters if the beam misalignment occurs at the location of such dosimeters. The real-time monitoring would help in the root cause and impact analysis.

Figure 1.

Left: Irradiation of a pallet with an X-ray beam. Right: Relative dose in the pallet as a function of beam misalignment in the X-ray converter.

Novel X-ray Flux Monitor

To mitigate the risk related to failures at the X-ray converter level, we designed and built an X-ray flux monitor (XRFM) with the intent of measuring the X-ray beam emitted from the X-ray converter in real time.

The detector consists of (1) a parallel-plate air-filled ionization chamber operating in proportional mode and surrounded by (2) a PMMA (polymethyl methacrylate) block, itself surrounded by (3) a thick lead collimator with a 10-mm circular opening facing the X-ray converter (Figures 2 and 3). When operating in unsaturated proportional mode, an air-filled ionization chamber generates an electrical current linearly proportional to the dose rate in air at the ionization chamber location.² The ionization chamber then is connected to an electrometer that measures the ionization chamber current and converts it into a voltage proportional to the dose rate.

Figure 2.

X-ray flux monitor (XRFM) installed in the back wall of the 7-MV X-ray line of the feerix facility.

Figure 3.

Left: Cross section of the X-ray flux monitor (XRFM). Middle: Temperature increase in the XRFM and beam current over time. Right: Collected current and corrected collected current from the ionization chamber. Abbreviation used: PMMA, polymethyl methacrylate.

Each photon from the X-ray spectrum has a specific energy and generates a specific current in the detector. The total current generated in the detector is the sum of all individual contributions. Therefore, provided that the X-ray energy spectrum remains unaltered, the collected current from the ionization chamber will be linearly proportional to the X-ray flux. For this reason, the detector is known as an XRFM. Its signal will vary with the beam current, the beam energy, the X-ray conversion ratio, the scan width, and the position, direction, and shape of the beam spot on the X-ray converter. As a result, the XRFM is a useful tool for checking the stability of the following five parameters:

1. A modification of the electron beam current will modify the XRFM’s signal proportionally.

2. An increase of the electron beam energy will increase the bremsstrahlung. The photon flux will increase (with a slight modification of the X-ray energy spectrum), leading to an increase of the XRFM’s signal.

3. Any mechanical modification of the X-ray converter leading to a modification of the X-ray conversion will alter the XRFM’s signal.

4. An increase of the scan width will reduce the photon flux and, hence, the XRFM’s signal.

5. A change in the position, direction, or shape of the beam spot will alter the photon flux at the detector level, leading to a change of the XRFM’s signal.

Experimental Setup

To evaluate the performance of such a detector, we built a prototype and tested it in the feerix facility of Aerial CRT in Illkirch, France. The feerix facility, which was constructed in 2019, is a high-energy and high-power irradiation plant. It has multiple beam lines that produce 10 MeV electrons and 5 and 7 MV X-rays generated by an electron beam accelerator (TT300 Rhodotron; IBA Industrial, Louvain-la-Neuve, Belgium).

The detector was tested on the 7-MV X-ray line, for which maximum power and scan width are 100 kW (14.3 mA) and 2.10 m, respectively. The XRFM was mounted to the concrete radiation shielding wall facing the X-ray scanner at the central location of the radiation field in both horizontal and vertical directions. The distance from the converter to the detector is 2.25 m, making it possible for a loaded tote to pass in between the convertor and the detector. Of note, this concrete wall is cooled with an integrated 18°C water serpentine.

The next section will describe how this geometry allows (1) process output measurement (consistency of the X-ray flux) and, potentially, (2) product photon attenuation signature—the latter being a novelty of this approach for enhancing radiation sterilization control and patient safety.

Results

Detector Qualification

Preliminary tests were performed to qualify the detector. The leakage current was measured (with the beam switched off) up to the nominal bias voltage of 300 V. It remained below 30 fA, which can be considered negligible. Thereafter, the detector response was measured for different beam settings without any product between the X-ray source and the detector. A linear behavior was observed in the entire range of operation, with a gain of 23 nA/mA and resulting in a scan width of 70 cm.

As expected, a temperature dependence was observed. Although the detector heats up with radiation, the air density reduces in the ionization chamber and the collected current reduces accordingly. Fortunately, this effect can be compensated. As illustrated in Figure 3, a thermistor was inserted in the detector, thereby allowing for correction of the output current with the measured temperature. As a result, a signal stability within ±0.5% was demonstrated for a one-hour operation at maximum beam power.

This qualification shows that the XRFM is an appropriate tool for verifying stability of X-ray flux on a daily basis. However, one can do more than that. The XRFM includes an acquisition system that runs at 1 Hz. This makes the XRFM suitable for observing X-ray flux during routine product processing.

Case of a Dummy Product

To study the XRFM response during product processing, a dummy product (consisting 9.4 g/cm² plywood and 4.5 g/cm² cardboard) was loaded on the tote (Figure 4). Then, the beam was switched on to a current of 3 mA and the pallet conveyed through the X-ray field at a speed of 0.5 m/min. Figure 4 shows the corresponding output signal of the XRFM. Each component of the dummy pallet can be clearly distinguished as it generates a flux fingerprint of the X-ray's attenuation. The sharp edges in the signal when moving from element to the next illustrate the effectiveness of the 10-mm collimator in selecting the straight-traveling photons. Even the hollow in the tote’s metallic uprights can be observed.

Figure 4.

Left: Dummy product loaded on feerix’s tote. Right: Signature of dummy product when processed at 0.5 m/min, 3 mA.

To evaluate the sensitivity of the detector, the dummy product was slightly modified by adding three thin elements (0.45 g/cm² copper, 2.3 g/cm³ lead, and 0.5 g/cm² polystyrene) and processed again. Figure 5 shows the comparison between the signal from the dummy products and the modified dummy product, resulting in two observations: (1) The reproducibility between both measurements demonstrated excellent short-term reproducibility of the XRFM. (2) Fluctuations of the signal on the order of 1% (corresponding to density fluctuations on the order of 5%) could be detected easily.

Figure 5.

Left: Dummy product modified with three thin elements. Right: Comparison of the signatures.

Case of a Real Product

The results shown in Figures 4 and 5 suggested not only that the XRFM could be used indirectly to verify the X-ray field properties and consistency but also that it could be used to check the product being processed. To further evaluate this, the tote was loaded with two rows of three Flexsafe STR50L bags (Sartorius, Aubagne, France) and processed in two different loading configurations (first with all six products in the upright position, then with one product flipped upside down). For this experiment, the beam current was raised to 7 mA while the conveyor speed remained at 0.5 m/min. Figure 6 compares the signal from the XRFM in the two configurations. Very good reproducibility can be seen, but at the position of the flipped product, a considerable deviation of 5.5% can be observed.

Figure 6.

Left: Two rows of three Flexsafe STR50L bags loaded on feerix’s tote. Right: Comparison of the signatures with one product flipped upside down.

Discussion

The results illustrated that the XRFM could be used for two distinct purposes. First, it could be used to verify any deviation of X-ray field properties (electron beam current, beam energy, scanning amplitude, or beam spot position, direction, or shape). This can be done either on a daily basis between product batches or even during product processing. Indeed, in X-ray processing, the products often are spaced by 10 cm, offering a sufficient gap to verify the beam between two products. The conveyor speed also could be easily verified by measuring the time interval between two products using the XRFM signal. This corresponds to an additional and independent verification of the machine parameter, and as such, we believe that the XRFM could contribute to machine-based release in X-ray sterilization of medical devices.

A second purpose could be to check the product composition itself. Indeed, the signal from the XRFM is a kind of signature of the product being processed. This signature would be gathered during PQ and used as reference data. As such, compared with the PQ product fingerprint, an abnormal product configuration could be detected. To that usage, high-speed data analysis and processing, as well as artificial intelligence, might be used.

To move forward, the next steps of this project will consist of developing a real-size demonstrator and testing it in an X-ray irradiator facility. Owing to the high selectivity of the collimator, the XRFM measures the X-rays from a specific point of the X-ray converter. As a real target typically is several meters in height, such a demonstrator would include several detectors.

When designing such a demonstrator, three technical challenges will need to be addressed. Because the latest generation of irradiator works at a power about five times higher than one at a feerix facility, the detector heating will be more critical than presented here and an appropriate temperature management system will need to be developed. Also, with a high-power beam, the ionization chamber could start saturating, which may require the development of an asymmetric ionization chamber.^6,7 Finally, the dose received by the XRFM over one year might be relatively important (>10 MGy). The lifespan of the XRFM needs to be optimized and assessed.

One could be tempted to place such a detector directly after the target, in order to play a role similar to routine dosimetry. Although this could be considered, the three technical difficulties noted previously would present even greater challenges. Also, the distance between the target and the product usually is set to the minimum reasonable value, leaving little room to place a detector. Finally, such a configuration would disallow the possibility of having a product fingerprint.

Conclusion and Future Opportunities

The introduction of active monitoring through the use of a detector array has tremendous potential and could enable much needed transformation in the radiation sterilization industry. The expansion, adoption, and implementation of this type of machine-based monitoring would transform many of the conventional practices in place today.

For example, this innovation enables the ability to actively monitor every tote, to verify whether the appropriate ionizing radiation field and intensity were present, and to deliver the required sterilization dose. It also enables machine-based decisions to support the acceptance of the process and product. As a result, the process can be monitored, compared, and trended in real time, every time. This innovation can also be used to assess and evaluate the impact of a process interruption.

In addition to routine process monitoring, this type of active monitoring paves the way for defining and characterizing the ionizing radiation field, which then can be compared with other ionizing radiation fields. These fields can be from different irradiators or from the same irradiator at different points in time (e.g., following a change to the irradiator). This comparison then could be used to determine field equivalence and, where similar conveyance through the field is present, process equivalence. The determination of process equivalence could simplify and add confidence to the assessment of changes to the irradiator.

These are just two examples of the potential benefits that further development of this technology can provide. Through the continued collaboration of industry partners, more benefits are bound to be realized.