WO2020208025A1

WO2020208025A1 - Device and method for sterilizing medical products by means of x-radiation

Info

Publication number: WO2020208025A1
Application number: PCT/EP2020/059906
Authority: WO
Inventors: Angela Baier-Goschütz; Christian Starke; Javier Portillo Casada; Frank-Holm Rögner; Ignacio Gabriel VICENTE GABAS
Original assignee: B. Braun Avitum Ag; Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.
Priority date: 2019-04-08
Filing date: 2020-04-07
Publication date: 2020-10-15
Also published as: JP2022528916A; EP3952926A1; CA3133881A1; DE102019109210A1; IL286705A

Abstract

The invention relates to a device comprising a radiation source and preferably a detector, between which a medical product is introduced, wherein the radiation source can be controlled by means of an open-loop and/or closed-loop control device and feedback from the detector or can be controlled by means of a result of dose mapping or a simulation. The method for sterilizing medical products comprises the following steps: introducing a medical product into a sterilization device; irradiating the medical product with a radiation source, preferably an X-radiation source, in the sterilization device; determining the radiation intensity at each position on the medical product; controlling and/or re-adjusting the radiation source according to the relationship, [determined in a reference measurement or simulation and] stored in the control device, between radiation intensity at the detector and minimum dose in the medical product at the corresponding point, such that the medical product is homogeneously irradiated and thus sterilized.

Description

Device and method for the sterilization of medical products using X-rays

description

[1] The invention relates to a device and a method for sterilizing 3-dimensional medical products with low-energy X-rays.

Background of the invention

[2] Sterility is a key requirement for many medical devices. A medical device is referred to as sterile if the probability that a viable microorganism is on or in the product is less than or equal to 10-6 (EN 556-1: 2001).

[3] A medical product refers to an object or a substance that is used for medical therapeutic or diagnostic purposes for humans., In contrast to medicinal products, the main intended effect of medical products is not primarily pharmacological, metabolic or immunological, but physical or physicochemical. Medical devices are therefore all instruments, apparatus, devices, software, materials or other objects used individually or in combination, which are intended by the manufacturer for people for the following purposes: detection, prevention, monitoring, treatment or alleviation of diseases; Detecting, monitoring, treating, alleviating or compensating for an injury or disability; Investigation, replacement or modification of the anatomical structure or a physiological process; Conception regulation and its intended main effect. Likewise, "products that are specifically designed for cleaning, disinfection or sterilization" of medical devices are considered medical devices. [4] One way to sterilize medical products is to use ionizing radiation (radiation sterilization). The methods used on a large scale for irradiating medical products are sterilization with gamma radiation (gamma sterilization), sterilization with accelerated electrons (e-beam sterilization, electron beam sterilization, beta sterilization) and sterilization with high-energy X-rays (X-ray sterilization, X-ray sterilization).

Gamma sterilization

[5] Gamma radiation is a particularly penetrating electromagnetic radiation that arises from the spontaneous transformations ("decay") of the atomic nuclei of many naturally occurring or artificially produced radioactive nuclides. Gamma radiation is the term used to describe short-wave photons that are generated by nuclear reactions, while X-rays result from the change in the speed of charged particles. Gamma radiation is often used to sterilize single-use medical devices such as syringes, needles, cannulas and IV sets as well as food, as its penetration depth is usually more than 50 cm. Radioisotopes, mostly cobalt-60 (60Co) or cesium-137 (137Cs), emitted with photon energies of up to 1, 3 or 0.66 MeV, are used technically.

[6] Gamma rays are electromagnetic waves (as well as light, infrared, X-rays or UV rays). However, gamma rays have a shorter wavelength (less than 0.005 nm) and therefore have more energy. During irradiation, this energy is transferred to the electrons in the molecules of the products, generating highly reactive radicals. This is why one speaks of ionizing radiation. These free radicals now break the DNA of the existing microorganisms so that they can no longer multiply and die. The irradiated product is therefore sterile. Since the gamma radiation only affects the electron shell of the molecules, it is physically impossible for the irradiated product itself to become radioactive.

[7] The irradiation process takes place in a special facility. The gamma rays required for this result from the decay of the radioactive isotope cobalt-60. This is stored in stainless steel cylinders within the system and represents the radiation source. During the irradiation operation, the radiation source is surrounded by the products to be irradiated on a conveyor system. In order to be able to enter the facility safely, the radiation source can be lowered into a water basin, the water column of which shields the rays. A great advantage is the good penetration ability of the gamma radiation, which makes it possible to sterilize the products in the final packaging. This simplifies the production process and ensures that the products are not re-contaminated by subsequent packaging work.

[8] The energy absorbed by the product or the irradiated object during irradiation is measured in kilogray (kGy). The energy absorbed by the product or the irradiated object depends on various factors (including exposure time, radiation intensity of the source, density of the material, packing density and size of the products, packaging material) and is checked using one or more dosimeters. It can thus be determined that each product receives the specified radiation dose.

Electron beam sterilization

[9] Electrons emitted by an electron source (cathode) are accelerated in a vacuum vessel in an electric field (direct voltage or alternating field) to almost the speed of light, either on curved paths (e.g. rhodotron, cyclotron, betatron) or linearly (cathode ray tube, linear accelerator, Cockcroft Walton accelerator, Van de Graaff accelerator). The accelerated electrons are then deflected (scanned) by an alternating magnetic field, if necessary, in order to be able to apply them to a defined area, if necessary additionally deflected by a static magnetic field, in order to achieve a product application deviating from the acceleration direction and then through a suitable exit window led by the vacuum to the ambient atmosphere and then to the product. The actual sterilization process takes place under ambient conditions. Electron energies of 70 keV to 10 MeV are used for electron beam sterilization. [10] In the e-beam irradiation process, the beam is generated with electrons generated in a hot cathode, which are introduced into the acceleration unit, the so-called cavity. With the rhodotron principle, they pass through the cavity several times with the help of magnetic deflection systems until they have reached the intended energy. In the electron beam treatment of medical products, the electrons are channeled out of the cavity with a maximum energy of 10 MeV. The generated electrons are set in a horizontally oscillating movement by a scanning magnet, whereby the electrons or the X-ray photons sweep over the entire product to be sterilized.

X-ray sterilization

[11] The spectrum of X-rays begins below extreme UV radiation at a wavelength of around 10 nm (over-soft X-rays) and extends down to less than 1 pm (over-hard or high-energy X-rays). The energy ranges of gamma and X-rays overlap in a wide range. Both types of radiation are electromagnetic radiation and therefore have the same effects with the same energy. The differentiating criterion is the origin: in contrast to gamma radiation, X-rays are not produced by processes in the atomic nucleus, but by high-energy electron processes. The radiation spectrum generated in X-ray tubes is a superposition of a continuous (bremsstrahlung) with a discrete (characteristic X-ray) spectrum. Photons from X-ray tubes have an energy of around 1 keV to 250 keV

[12] In the case of electron beam sterilization and X-ray sterilization, an electron accelerator generates high-energy electrons. In electron beam sterilization, the electrons are used directly for sterilization. When the product is treated with X-Ray technology (X-ray technology), the electrons do not leave the vacuum vessel, but are accelerated onto a metal plate, the so-called target. When interacting with this target, part of its energy is converted and emitted in the form of X-rays, which are used for product sterilization. Systems with electron energies of 5 - 7 MeV are used for X-ray sterilization. [13] X-rays, like gamma radiation, represent a very penetrating type of radiation that allows larger volumes and higher densities to be sterilized than with e-beam technology. Gamma and X-ray sterilization are suitable for the sterilization of packaged goods due to the high penetration depth of the photons.

Disadvantages of radiation sterilization

[14] The 3 described sterilization processes have specific disadvantages. Systems for gamma sterilization are dependent on a radioactive isotope. Both the production of Co-60 by neutron activation of Co-59 in nuclear reactors and the transport and disposal of the decay products are associated with safety risks and high costs. In addition, long-term availability cannot be guaranteed.

[15] Electron beam sterilization is only suitable for medical products of small dimensions and densities due to its low penetration capacity compared to gamma or X-rays of the same energy.

[16] The problem with X-ray sterilization is that a large part of the electrical energy used is not converted into X-ray radiation, due to the principle involved, but instead drops off as heat at the X-ray target, which results in a low level of efficiency. An expensive high-energy electron accelerator is also necessary for electron beam and X-ray sterilization systems.

[17] For all 3 procedures, extensive shielding measures are necessary in order to guarantee adequate radiation protection. Gamma, electron beam and X-ray sterilization systems are therefore operated in a radiation protection bunker. The construction of compact sterilization units that can be integrated directly into the manufacturing process of medical products is difficult and very time-consuming with the conventional sterilization processes described.

Low-energy X-rays [18] One possibility for realizing a sterilization process that is based on the sterilizing effect of ionizing radiation and that can be integrated into the continuous production process of many medical products is to use ionizing radiation with lower energy. This has two main advantages. On the one hand, the measures for shielding the radiation are reduced, since the depth of penetration of the radiation decreases with decreasing energy. On the other hand, no high-energy electron accelerators are required to generate low-energy X-rays, but compact electron guns or X-ray tubes can be used. With these devices, electron energies of up to about 800 keV can be generated. In the following, the term “low-energy” or “soft” X-ray radiation denotes the energy range up to this limit.

[19] Low-energy X-rays can be generated without the use of a high-energy electron accelerator and require less effort for radiation shielding, which enables the implementation of a sterilization process that can be integrated into the continuous production process of many medical products.

Depth of penetration

[20] In order to sterilize a medical device with ionizing radiation, the radiation must be able to penetrate sufficiently deep. Accelerated electrons (in electron beam sterilization) have a high probability of interaction with matter due to their particle properties. Their depth of penetration is therefore low. For example, electrons with an energy of 600 keV have a penetration depth of approx. 2 mm in polyethylene and are therefore only suitable for the sterilization of 2-dimensional, i.e. H. very thin medical devices or the sterilization of surfaces. For the sterilization of 3-dimensional medical products, i. H. Medical products whose height / thickness is in the same order of magnitude as their length and width and in the range of centimeters or greater are therefore not suitable for low-energy electrons.

[21] In contrast to electrons, photons (gamma / X-rays) have neither a charge nor a mass. The interaction probability of Photons when penetrating matter are therefore much lower than with electrons. Gamma or X-rays can therefore penetrate much deeper into matter than electron beams of the same energy. Photon energies in the low two-digit keV range are sufficient to penetrate many 3-dimensional medical products such as dialyzers with photon radiation. An increase in the energy of the photon radiation leads to an increase in the dose homogeneity. If the absorbed dose entered is too homogeneous, doses that are so high that the material is damaged can occur at points at which dose maxima develop. These can affect the usage properties of the medical device such as B. reduce the biocompatibility.

State of the art

[22] WO 2014/132049 A2 (Apparatus for the generation of low-energy X-rays) discloses a device that is used to generate X-rays with low energy, as well as a method for sterilizing products with this device. As an application for sterilization with this device are u. a. Called medical devices and pharmaceutical products. The device differs in some points from a classic X-ray tube (for example the X-ray radiation generated at the anode (X-ray target) is scattered back to the cathode and penetrates it, whereas in an X-ray tube the anode has a defined angle and the X-ray radiation is emitted at an angle).

[23] GB 2 440 310 A (Surface Sterilization) discloses a device which generates X-rays with an energy of less than 50 keV. The device can be used to sterilize surfaces and thin materials.

[24] EP 2 668 963 A1 (device for sterilizing containers with sterilization checking) discloses a device for sterilizing containers which are conveyed past a sterilization device with a transport device, where they are sterilized with radiation. The containers are then moved past another facility that checks the success of the sterilization. Electron radiation is named and explained as the preferred type of radiation for sterilization, that X-rays or UV radiation can also be used to sterilize the containers. In addition to containers, no further application examples are given. The purpose of the procedure is exclusively to sterilize surfaces.

[25] WO 2008/129397 A2 (Sterilization System for PET Containers and Bottles) discloses a system for the sterilization of containers made of PET. Electron beams are used for sterilization. The sterilization effect of the electron beams is supported by the fact that X-ray targets are arranged within the system, which convert the incident electron beams into X-rays.

[26] WO 93/17446 A1 (A microwave X-ray source and methods of sterilization) discloses a device which generates X-rays by means of a cyclotron resonance plasma. One of the applications disclosed is the sterilization of medical equipment and instruments.

Disadvantages in the prior art

[27] X-ray sources in the low-energy range are mainly used for analytical purposes. They are therefore designed to achieve the highest possible image quality. Sterilization, on the other hand, requires the generation of high radiation power in order to achieve the required level of sterility security (SAL) in the shortest possible time. The use of commercial X-ray tubes for the sterilization of medical products is therefore not expedient.

[28] Conventional sterilization methods for medical products based on the sterilizing effect of ionizing radiation (gamma, electron beam and high-energy X-ray sterilization) can only be integrated into the production process of medical products with great effort. The main reason for this is the high radiation energy that occurs, which requires complex radiation protection measures. In the case of electron beam and high-energy X-ray sterilization, the use of a high-energy electron accelerator with high radiation energy and power is also required, which takes up a lot of space and is cost-intensive. Object of the invention

[29] The present invention is therefore based on the object of providing a device and a method for sterilizing medical products that are compact, avoid the use of radioactive substances, are easy to control and regulate, have high sterilization efficiency, and enable a high penetration depth or a homogeneous dose is achieved in the product to be sterilized.

[30] As explained above, low X-ray energies lead to a reduced homogeneity of the dose entered in a 3-dimensional medical product, which can lead to material damage in these areas if a local overdose is then necessary. Furthermore, many medical products are inhomogeneous in terms of their geometric shape and material composition. H. There are areas in which the medical product has a greater thickness and / or density than in other areas, which can also cause high local overdoses and thus material damage.

[31] It is therefore preferably also an object of the invention to irradiate an inhomogeneous medical product / 3-dimensional medical product as homogeneously as possible even with low X-ray energies or to reduce the overdose factor (max. Locally applied dose in the product / target dose).

Brief description of the invention

[32] The object or objects of the invention is / are achieved by a method for sterilizing medical products according to claim 1 and a device for sterilizing medical products according to claim 9.

The device for sterilizing at least one medical product has at least one radiation source, preferably at least one detector for detecting a radiation intensity, at least one holder for holding a medical product in front of the radiation source, preferably between the radiation source and the detector and at least one control unit Control or regulation of the radiation source and preferably the holder. Whereby the intensity of the radiation from the radiation source by the control unit, preferably continuously or clocked, can be regulated by means of a feedback and / or controlled by means of a feedforward control such that the radiation intensity at each position of the medical product assumes a predetermined or predeterminable value that is minimally necessary for the sterilization. In other words, the intensity of the radiation of the radiation source can be regulated by the control unit, preferably continuously or clocked, by means of a feedback and / or by means of a feedforward control so that a predetermined optimal intensity distribution of the X-ray radiation is achieved that is necessary to achieve the required Sterilization dose at every point of the medical device, a more homogeneous dose distribution in the medical device (minimization of the overdose factor) and a reduced irradiation time (= time to achieve the required sterilization dose). A predetermined optimal intensity distribution of the X-ray radiation is preferably determined experimentally by means of dose mapping or with a simulation. Every position of the medical device means at every position in / on the 3-dimensional body of the medical device.

The device for sterilizing at least one medical product can also be referred to as a sterilization device or sterilization unit or as a sterilization device or sterilization unit, provided and adapted for the sterilization of medical products.

[35] The radiation source is preferably a directed radiation source, preferably an electromagnetic radiation source, preferably an X-ray source and particularly preferably a low-energy X-ray source, which is provided and adapted to provide / generate primary electrons with an energy of 100 to 800 keV. The radiation source is also provided and adapted to set the radiation intensity / the absorbed dose of the radiation locally / spatially resolved / locally determined / individually, that is to say clocked or continuously within an impinged irradiation area. The absorbed dose entered in the medical product can thus be controlled or regulated locally, which generally results in an inhomogeneous / controllable irradiation intensity within the medical product. [36] The detector is preferably provided and adapted to detect the radiation from the radiation source. The detector is also preferably an area detector (detector with a large area sensor), preferably an X-ray detector or an area X-ray detector. The detector is further preferably a digital detector which generates data signals and forwards them to a control device. The radiation source emits radiation and sends the radiation out in a directed manner, the detector is preferably placed in the directed radiation / in the beam path. This means that the detector is irradiated by the radiation source. The detector preferably has at least the size required to be able to detect the smallest dimension of the shaded area, preferably at least the size required to detect the entire area shaded by the medical product, in order to be able to draw conclusions about the absorbed dose in the entire medical product. If the detector is moved in the direction of the other dimension, or if the medical device moves in this direction, the same statement can be obtained.

[37] A medical device is generally known and is defined in the introduction. The method and the device are provided and adapted to sterilize at least one medical product at a time.

The device has a holder / clamping device / holding device / medical product holder, which is preferably provided and adapted to hold at least one medical product, particularly preferably between the radiation source and the detector. The holder further preferably has a transport device by means of which the medical product can be transported between the radiation source and the detector. In other words, the transport device moves the medical product into the beam path for a certain period and then out again. Furthermore, the holder preferably has a movement device / rotating device / rotating device that rotates or rotates the medical product about at least one axis or causes it to wobble. In other words, the at least one medical product can be fixed / stabilized / held in the holder and, preferably about the longitudinal axis, rotatable. The holder is in the directed radiation / dem Brought in the beam path of the radiation source, preferably an X-ray beam path. The holder and thus the medical product are arranged between the radiation source and the detector. In one variant, the holder can also insert only part of the medical product into the beam path if its size exceeds the irradiated area in the beam path, but it can also insert a single or multiple medical product into the beam path at the same time and thus sterilize it. Furthermore, the holder holds the medical device in such a way that the irradiation of the product is not hindered or any hindrance is minimized. The holder preferably holds the medical product or the medical product is clamped into the holder in such a way that the holder does not overlap the medical product in the direction of irradiation. In other words, the medical product and the holder are not arranged one behind the other in the radiation direction, but rather parallel to it. The medical product is preferably held or clamped by the holder on its outer surfaces.

In a further aspect of the invention, the holder has a transport device with which the at least one medical product can be transported through a beam path between the X-ray source and the X-ray detector. In other words, the at least one medical product can be transported mechanically / electromechanically through the beam path, preferably by means of a conveyor belt or the like.

[40] The device can thus consist of a radiation source and a detector between which the medical product is introduced, but also of several radiation source-detector pairs, the medical product being arranged between them. The device preferably has at least two, preferably three, x-ray sources and x-ray detectors.

[41] The process for sterilizing medical devices has the following steps:

a. Introducing a medical product into a sterilization device;

b. Local irradiation of the medical product with a radiation source of the sterilization device; c. Local determination of the radiation intensity by means of dose mapping or with simulations,

d. Controlling or regulating the radiation source by a control unit so that at least one radiation intensity that is minimally necessary for sterilization is achieved at every position of the medical product. In other words, a predetermined optimal intensity distribution of the x-ray radiation is achieved, which leads to the required sterilization dose being reached at every point of the medical product, a more homogeneous dose distribution in the medical product and a reduced irradiation time.

[42] The medical product can be introduced into the sterilization device / irradiation device / device for sterilizing medical products manually and / or mechanically, preferably between the radiation source and detector or the sensor of a detector. Further preferably, the introduction and / or a subsequent change of the medical product takes place automatically, preferably computer-controlled. In addition, the medical product is further preferably held / fixed / stored by a holder / clamping device between the radiation source and the detector. The holder has a movement device and / or rotation device and / or a transport device. The rotation device of the holder rotates the medical product around at least one axis and the transport device changes or transports the medical product.

[43] The local / individual irradiation, preferably stepwise and / or continuously / continuously, of the medical product (along / along the medical product) with a radiation source of the sterilization device is preferably carried out by means of a directed radiation source or electromagnetic radiation source or X-ray source or low-energy X-ray source or A low-energy X-ray source, which is provided and adapted to use a primary electron with an energy of 100 to 800 keV. Local irradiation is to be understood as irradiation with local intensity resolution, which irradiate different areas / locations / locations / positions of an object or medical product with radiation / radiation intensity / radiation dose / dose / energy dose / photon energy that are different relative to / from one another can. This means that the medical device can be irradiated with a different intensity at each point / individual points / other points.

[44] The determination of the radiation intensity at each position of the medical device shows how much of the radiation emitted by the radiation source is absorbed by the medical device.

[45] The radiation source is controlled or regulated in such a way that at every position of the medical device a minimum radiation intensity required for sterilization is achieved in the medical device. In other words, a previously determined optimal intensity distribution of the X-rays is achieved, which is necessary to achieve the required sterilization dose every point of the medical device, a more homogeneous dose distribution in the medical device and a reduced irradiation time. In yet other words, an (intensity) model for irradiation for the medical device can be set up in advance and loaded onto a storage unit of the control unit / CPU so that the Control unit controls the spatial resolution of the radiation source. The (intensity) model can be determined by a simulation / calculation or reference measurement.

In a further aspect of the invention, the medical product is irradiated from several sides and / or rotates around at least one axis, preferably in / on / with the holder. This means that the medical product is introduced into a sterilization device with several radiation sources and / or rotates on / in / with the holder, preferably around its own axis. In addition to the multiple radiation sources, the device can also have multiple detectors.

[47] In the variant with several radiation sources, the medical device is irradiated from 2, 3 or more sides at the same time. The device for generating the low-energy X-ray radiation is accordingly designed several times and arranged uniformly offset around the medical product. Multi-sided irradiation has the advantage that the use of multiple X-ray sources with the same power as with one-sided irradiation shortens the sterilization time. Alternatively, by reducing the power of the individual X-ray sources, the thermal load on the targets is reduced and thus their service life is increased. Since the medical device does not have to be rotated, the holder can be constructed in a simpler way. The dose homogeneity increases with an increasing number of X-ray sources that are arranged around the medical device. The rotation of the medical device during the irradiation is comparable to the arrangement of an infinite number of X-ray sources around the medical device and therefore provides the best dose homogeneity.

[48] In a further alternative embodiment variant, the structure of two or more-sided irradiation is selected and arranged two or more times one behind the other. This results in a sterilization tunnel through which several medical products can be transported by means of a transport device and thereby irradiated and thus sterilized. With a given target dose, the transport speed and thus the achievable throughput are dependent on the intensity of the radiation sources and on the number of radiation sources arranged one behind the other in the transport direction.

[49] Further design variants can be obtained by combining the design variants explained above. For example, the rotating irradiation can also take place from two or more sides in order to achieve a high dose homogeneity with a reduced irradiation time or reduced thermal load on the target.

In a further aspect of the invention, the medical product is irradiated in such a way that the radiation intensity of the X-ray radiation varies locally and is adjusted so that the dose in the medical product is distributed as homogeneously / evenly as possible. This means that at least the minimum dose occurs at every point / every position of the medical device. A specific intensity distribution of the transmitted X-ray radiation is preferably established, which can be measured by a detector located in the beam path behind the product in order to readjust the radiation source accordingly if necessary. This distribution of the radiation intensity is called the optimal intensity distribution.

As already explained above, the radiation source can be controlled or regulated by the control unit, so that the optimal intensity distribution is reached at every position of the medical device. The control takes place in that the position and the shape of the medical product is stored in the device for sterilization on the control device and the medical product is irradiated with a previously determined intensity by the radiation source in a spatially resolved manner. An (intensity) model (a model for spatially resolved irradiation with a predetermined intensity) is thus set up for the respective medical product in advance. The (intensity) model is determined by a reference measurement or by means of a simulation. The reference measurement includes, among other things, a dose mapping.

[52] In the case of dose mapping, a test sample is equipped with dosimeters (e.g. alanine dosimeters). The dosimeters are placed wherever minimums and maximums of the dose are expected. The medical device is then irradiated and the dosimeter is evaluated.

[53] To determine the optimal intensity distribution, the medical product is divided over its length into several areas that differ significantly in their geometry and / or material composition. For each area i a factor kJ is determined by which the intensity of the X-ray radiation in the corresponding area is multiplied in order to achieve the optimal intensity for this area. kJ is chosen so that the minimum dose in the area under consideration corresponds to the required sterilization dose. To determine the factor kJ, the occurring minimum dose D_min, i must be determined for each area, either by means of a dose mapping or by means of simulations. The harmonic mean D_min, HM is calculated from the dose minima D_min, i of each range:

[54] The factor kJ for each range results from the harmonic mean of the minimum doses divided by the dose minimum of the respective range:

The data obtained in this way for the intensity distribution are valid for all medical devices of this type and can be used as long as the geometry and materials of the medical device as well as the parameters of the sterilization apparatus (radiation energy, distance between target and medical device, etc.) remain unchanged.

[55] The simulation can be a Monte Carlo simulation or a simulation based on the law of attenuation or the like.

[56] The detector can be used to check the dose introduced into the medical device in order to release the medical device immediately after irradiation. For this purpose, the determined intensity distribution is set in a pre-test and a medical device equipped with dosimeters is irradiated. Because the medical product is located in the beam path, a “shadowing” occurs on a detection surface of the detector. The doses measured at the detector during the irradiation are recorded. The dosimeters in the medical device are then evaluated and checked to determine whether the required sterilization dose has been achieved at each point. If this is the case, then the data recorded by the detector can be used for all subsequent irradiations of medical devices of the same type or size. During each sterilization process, the doses determined on the detector are compared with the doses recorded. If the deviations do not exceed a specified limit, the irradiated medical devices can be designated as sterile and approved.

The variation of the intensity of the radiation source or an electron beam striking an X-ray target over the surface of the target allows a spatially resolved adaptation of an X-ray field to the medical product. The holder allows for at least one medical product to move the medical product in space, preferably an axial rotation along an axis. The detector enables the measurement of the X-rays absorbed by the medical device. A shield of the device for sterilization protects the Operator. The method for using this sterilization unit for the sterilization of medical products is carried out using the above device. The X-ray field is, so to speak, adapted to the medical product to be sterilized, also continuously over time, if the medical product rotates in order to adjust the energy dose. The intensity distribution is preferably determined prior to the serial irradiation on test samples of the medical product to be irradiated. For this purpose, either a can mapping or computer simulations (e.g. Monte Carlo simulation) are carried out.

[58] The shielding of the sterilization unit is designed in such a way that the production staff and the environment are protected from the effects of radiation and the applicable laws, ordinances and standards are observed.

[59] The holder is designed so that it can hold at least one or more medical devices at the same time and does not obstruct the desired exposure to radiation. In one embodiment variant, the holder makes it possible to move the medical product during the irradiation, to rotate it in the preferred embodiment for the example product. With this system, the dose inhomogeneity due to the depth dose distribution that occurs at low energies because of the limited penetration depth of the X-ray radiation can be improved. The dose homogeneity can be increased by increasing the number of X-ray sources that are arranged around the medical device. The rotation of the medical product corresponds to an infinite number of X-ray sources and thus represents the best possible case in terms of achieving high dose homogeneity. The holder is preferably designed so that fully automatic loading and unloading of the medical product (s) is made possible.

The invention makes it possible to achieve a high dose homogeneity despite the low energy of the X-ray radiation. Furthermore, due to the low radiation energy and the associated lower required shielding measures, for example in comparison to Co-60 gamma radiation systems or 10 MeV e-beam radiation systems, the invention can be integrated into the continuous production process of medical products. The dependence on service providers who provide the Sterilization with gamma radiation, high-energy electron beams or high-energy X-rays is not required. The system is easily scalable: depending on the throughput of the production system, the necessary number of sterilization units is purchased. A high level of production reliability can be achieved through the redundant operation of several sterilization units. The sterilization with low-energy X-ray radiation also has the known advantages of methods that are based on the sterilizing effect of ionizing radiation. This includes avoiding the use of toxic substances such as B. ethylene oxide, the possibility of sterilization in the final packaging and parametric product release based on the applied absorbed dose.

[61] Process monitoring is preferably provided to monitor the sterilization process. This consists of at least one X-ray detector which is arranged in such a way that it is possible to draw conclusions about the absorbed dose absorbed in the medical product. For this purpose, electronically readable detector plates are preferably arranged in such a way that the medical product to be sterilized is located between the X-ray source and the detector plates. The size of the detector plate is chosen so that it fully detects the X-ray radiation shadowed by the medical device and also covers an area in which the X-ray radiation was not attenuated by the medical device. The difference between the intensity of the X-ray radiation attenuated by the medical device and the non-weakened X-ray radiation allows conclusions to be drawn about the energy absorbed by the medical device. A method for the sterilization of 3-dimensional medical products with low-energy X-rays can be carried out in the following steps.

[62] For the sake of simplicity, the specific sequence of the procedure is only explained for a single medical device:

• Provision and placement of the medical device in a radiation-resistant sterile barrier system / packaging suitable for sterilization with ionizing radiation (optional: removal of oxygen from the packaging for medical devices where radiation in the presence of oxygen can cause material damage); • Equipping the sterilization unit with the packaged medical product, preferably with an automatic handling system

• Initiation of all necessary measures to ensure the radiation safety of the arrangement;

• Irradiation of the medical device with locally differing radiation intensities according to the description above over a defined irradiation time in order to achieve the required irradiation dose, e.g. is required according to national standards Removal of the sterile medical device, preferably with an automatic handling system;

• Evaluation of the data from the X-ray detectors and dosimetric approval of the medical device.

The device has a radiation source and preferably a detector, between which a medical product is inserted, the radiation source being controllable by means of a control and / or regulating device and a feedback of the detector or by means of a result of dose mapping or a simulation is controllable. Preferably, when regulating the radiation source by means of the spatially resolved intensity, it is regulated in such a way that the setpoint values of the spatially resolved detector are achieved. The method for sterilizing medical products comprises the steps: introducing a medical product into a sterilization device; Irradiating the medical product with a radiation source, preferably an X-ray source, of the sterilization device; Determination of the radiation intensity at each position of the medical device, control and / or readjustment of the radiation source according to the relationship between the radiation intensity at the detector and the minimum dose in the medical device at the corresponding point [determined in a reference measurement or simulation and stored] in the control device, so that the medical device is homogeneous is irradiated and thus sterilized.

[64] Description of the figures

Figure 1 shows abstractly the structure of the device. FIG. 2 shows an X-ray source with a solid target in a vacuum (classic X-ray tube).

FIG. 3 shows an X-ray source with a passage target.

FIG. 4 shows a simplified model for the effect of an adapted one

Intensity distribution.

Figure 5 shows the targeted change in the intensity distribution of the

X-ray field as a function of the geometry and material composition of a medical product (here an example for a dialyzer).

FIG. 6 shows the increase in dose homogeneity by increasing the number

X-ray sources.

Figure 7 shows a second embodiment of the invention, a three-sided

Irradiation (holder and shield not shown).

Figure 8 shows a third embodiment of the invention, a two-sided

Arrangement of several X-ray modules to form a sterilization tunnel (X-ray detector, holder and shield not shown)

[65] FIG. 1 abstractly shows the structure of the device for sterilizing medical products according to a preferred exemplary embodiment of the invention. An X-ray source 2 (radiation source) is introduced into a device for sterilization 1. The X-ray source is controlled by a CPU / control unit 3. The representation in FIG. 1 is schematic and the CPU 3 is actually located outside the radiation space. The

Radiation source 2 emits directed radiation 4 with a locally determined energy dose or intensity. A detector 6 is located in the direction of the directed radiation 4. In front of the detector 6, a medical product 8, for example, is placed in the directed radiation 4, that is, between the radiation source 2 and the detector 6 a dialyzer. The medical product 8 is held by a holder 10 and can also be rotated by this.

[66] FIG. 2 shows an X-ray source with a solid target in a vacuum (classic X-ray tube). The radiation source consists of an electron source 12 which accelerates electron radiation 14 in a directed manner. The electron radiation 14 strikes an X-ray target 16 and generates directed X-ray radiation 4 there. The X-ray radiation exits the vacuum through the exit window 18.

[67] FIG. 3 shows an X-ray source with a transmission target. The structure of the X-ray source in FIG. 3 is analogous to that in FIG. 2, with the exception that the electron radiation does not strike a massive X-ray target and the X-ray radiation is generated there, but that the electron radiation 14 hits a very thin X-ray target that also serves as an exit window 22 hits in that the directed X-ray radiation 4 is generated in the direction of the primary electron radiation.

In other words, the arrangement of the X-ray target 16 and 22 can be possible in 2 variants: The X-ray target can be designed as a massive target (thick target) 16, which is located within the vacuum vessel of the

Electron accelerator is located (this structure corresponds to the classic X-ray tube). The X-ray target can, however, also be designed as a thin target (transmission-type target) 22.

The electron source 12 has subsequently, that is between the electron source 12 and

Target 16, 22 a system for the spatially resolved increase or decrease of the intensity of the electron current impinging on the X-ray target 16, 22 in defined areas. The X-ray target then converts the kinetic energy of the accelerated electrons into X-ray radiation with a spatially resolved increase or decrease in intensity.

The X-ray target 16, 22 is preferably made of a metal with a high atomic number. One embodiment is tungsten because of its high level X-ray yield and the very good heat resistance. Another embodiment is silver, since its emission lines of the characteristic X-ray radiation are in a lower energy range than with tungsten. In this lower energy range, the mass energy absorption coefficient pen / p of the materials of the medical product is greater than at higher energies, as a result of which the energy dose entered into the medical product is greater, which can lead to an increased efficiency of the irradiation process. The X-ray target 16, 22 preferably has a device for cooling it.

[71] FIG. 4 shows the energy doses that occur, greatly simplified, by means of two individual, 1-dimensional, parallel, monoenergetic X-rays 24 and 26. Both X-rays penetrate a medical product 8 consisting of a homogeneous material, the thickness of the material being that of beam 24 is penetrated, is only half the thickness of the material through which beam 26 penetrates. A detector 6 is shown in the beam direction behind the medical product 8. In the high density area, a longer irradiation time is required to achieve the sterilization dose than in the low density area. However, since the medical product 8 is irradiated as a whole, each area experiences the same irradiation time. The area of low density is thus irradiated for longer than would be necessary to achieve the sterilization dose.

[72] FIG. 5 shows the targeted change in the intensity distribution of the X-ray radiation field depending on the geometry and material composition of the medical product 8, here as an example for a dialyzer (top picture: schematic representation of the medical product, bottom picture: location-dependent radiation intensity) in the area of the PUR potting ( 9) a dialyzer has a higher density at both ends of the dialyzer than in the middle area. In order to achieve a more homogeneous dose input, the intensity of the radiation field is increased in the high density area and reduced in the low density area (total intensity or power remains constant). As an alternative or in addition to this, a homogeneous dose input can also be achieved by estimating a longer irradiation time and / or rotating the dialyzer during irradiation becomes. This results in a more homogeneous dose distribution overall. The irradiation time over the entire medical device is reduced. This reduced exposure time in combination with the reduced radiation intensity in the low density range leads to a lower maximum dose in the low density range, which reduces potentially harmful radiation-induced material changes. In the high density range, however, the maximum dose remains unchanged, since the reduced irradiation time and the increased radiation intensity are balanced out. The reduced exposure time results in an increased efficiency of the process. In FIG. 5, the dialyzer connections of the dialyzer are drawn in upwards (leading away from the image of the radiation intensity), while the radiation is radiated onto the drawing in the image plane.

[73] FIG. 6 shows the increase in dose homogeneity by increasing the number of X-ray sources, a rotation of the medical product in front of an X-ray source representing the best case (here simulated with 16 sources). Simulation parameters: massive tungsten target, target angle: 45 °, electron energy: 400 keV, 1 mm Al filter, distance x-ray source (s) to the center of the dialyzer: 12 cm, the dose absorbed in water is shown. A shows the absorbed dose from one source on the left, B shows the absorbed dose from two sources, left and right, and C shows the absorbed dose from 16 sources evenly distributed around the medical device.

[74] FIG. 7 shows a second embodiment of the invention, more precisely a three-sided irradiation of the medical product 8 (holder and shield not shown). The medical product 8 is irradiated with a directed x-ray 4 from three radiation sources 2 (at a circular angle of approx. 120 °) distributed uniformly at an angular distance on a plane. A detector is located behind the medical product 8 in the direction of the X-ray radiation.

[75] FIG. 8 shows a third embodiment of the invention, more precisely an embodiment in which a two-sided arrangement of several X-ray modules to form a sterilization tunnel is shown (X-ray detector, holder and shield not shown). The medical products 8 are irradiated from two opposite sides by radiation sources 2 and in a transport direction shown schematically 28 transported by means of a transport device (not shown). The medical products 8 are thus conveyed through a “radiation tunnel”. A different arrangement of the radiation sources 2, for example as shown in FIG. 7, would also be possible here.

List of reference symbols

1 device for sterilization

2 radiation source

3 CPU

4 directional X-rays

6 detector

8 medical device

10 holders

12 electron source

14 electron beams

16 X-ray target

18 exit window

20 vacuum

22 exit window with integrated X-ray target

24 low intensity x-ray

26 high intensity x-ray beam

28 Direction of transport

Claims

Expectations

1. A method for sterilizing medical devices (8), comprising the steps:

a. Introducing a medical product (8) into a sterilization device (1);

b. Step-wise or continuous local irradiation of the medical product (8) with a radiation source (2) of the sterilization device (1);

c. Local determination of the radiation intensity in the medical device (8), using dose mapping and / or a simulation,

d. Controlling or regulating the radiation source (2) by a control device (3) so that a radiation intensity that is minimally necessary for sterilization is achieved everywhere at every position of the medical product (8).

2. The method according to claim 1, characterized in that the medical product (8) is irradiated from several sides simultaneously and / or rotates about an axis.

3. The method according to claim 1 or 2, characterized in that the radiation intensity is spatially resolved different and / or variable.

4. The method according to claim 1, characterized in that the medical product (8) is introduced between the radiation source (2) and a detector (6).

5. The method according to any one of claims 1 to 4, characterized in that the regulation of the radiation source (2) takes place by means of feedback from the detector (6).

6. The method according to any one of claims 1 to 5, characterized in that the detector (6) has an area which is larger than the medical product (8), and determines the radiation intensity.

7. The method according to one of claims 1 to 5, characterized in that the radiation source (2) is controlled by means of the simulation or by means of the can mapping.

8. Device (1) for sterilizing at least one medical product (8), having

- at least one radiation source (2),

- Preferably at least one detector (6) for detecting a

Radiation intensity,

- At least one holder (10) for holding a medical product (8) in front of the radiation source (2), preferably between the radiation source (2) and the detector (6) and

- At least one control unit (3) for controlling or regulating the radiation source (2) and preferably the holder (10),

characterized in that

the intensity of the radiation from the radiation source (2) by the control unit (3) can be continuously or cyclically regulated by means of feedback and / or by means of a feedforward control so that at each position of the medical product (8) at least one radiation intensity that is minimally necessary for sterilization is achieved. .

9. Device (1) according to claim 8, characterized in that the radiation source (2) is provided and adapted to provide photon energy of 100 to 800 keV.

10. Device (1) according to one of claims 8 or 9, characterized in that the holder (10) has a transport device by means of which the medical product (8) can be transported between the radiation source (2) and the detector (6).

11.Vorrichtung (1) according to any one of claims 8 to 10, characterized in that the holder (10) is rotatable, preferably about at least one axis.

12. Device (1) according to one of claims 8 to 10, characterized in that the device (1) has at least two, preferably three, radiation sources (2) and detectors (6).

13. Device (1) according to one of claims 8 to 12, characterized in that the control unit (3) has a storage medium on which the method steps according to claim 1 are stored.

14. Device (1) according to one of claims 8 to 13, characterized in that the radiation source (2) is provided and adapted to provide X-rays from a primary electron beam with an energy of 100 to 800 keV.