METHOD FOR DETERMINING THE EFFECTIVENESS OF A STERILIZATION METHOD FOR A MEDICAL PRODUCT IN A STERILIZER, DATA PROCESSING SYSTEM, COMPUTER PROGRAM PRODUCT, AND MEDICAL PRODUCT

Abstract

A process is presented for determining the effectiveness of sterilization processes for medical devices, with the steps of: providing a data structure, wherein the data structure represents a grid formed of a plurality of three-dimensional cells, recreating the medical device arranged in the sterilizer in the data structure in such a way that a first plurality of cells of the grid represent a body of the medical device and that a second plurality of cells represent an interior of the sterilizer which is not occupied by the body of the medical device, recreating an initial state in the data structure in such a way that each cell of the second plurality of cells is assigned data with respect to the temperature prevailing at the location of the cell, the quantity of a first medium located in the area of the cell and the quantity of a second medium located in the area of the cell, recreating, step by step, changes in the temperature, the quantity of the first medium and the quantity of the second medium occurring in each cell of the second plurality of cells during the sterilization process, and calculating a reduction of a germ load achieved in each cell of the second plurality of cells during the sterilization process taking into account the prevailing temperature, quantity of the first medium and quantity of the second medium in the respective cell in each step. Furthermore, a data processing system as well as a computer program product for carrying out the process are presented.

Description

The invention relates to a process for determining an effectiveness of a sterilization process for a medical device or a packaged medicinal product in a sterilizer. For sake of brevity the following disclosure mainly refers to medical devices, while each reference to medical devices shall also include packaged pharmaceutical products.

Sterilization processes are used to sterilize medical devices or packaged medicinal products prior to their use, thus to rid them of potentially harmful germs. Known sterilization processes comprise steam sterilization, dry heat sterilization, autoclaving, gamma sterilization, electron beam sterilization, ethylene oxide sterilization and plasma sterilization. Within the framework of this application, medical device also denotes medicinal products, in particular packaged medicinal products, further in particular medicinal products packaged in bags, further in particular solutions and devices for peritoneal dialysis packaged in bags.

The sterilization is usually effected in a sealed sterilization chamber of a sterilizer, into which the medical device is introduced.

In order to avoid endangering patients on whom the medical device is to be used, it must be ensured that the medical device is actually sterile, i.e. substantially free of germs, after the sterilization process has been carried out.

While the fundamental effectiveness of known sterilization processes has been sufficiently proven scientifically, the actual effectiveness of a sterilization process when applied to a particular medical device is dependent on many parameters, including shape and material properties of the medical device, and on the selected process parameters of the sterilization process, e.g. the temperature profile, quantities of media used and the process duration.

As individually checking the sterility of a medical device is impossible in practice, without in the process at least limiting the availability for use of the medical device, proving the sterility is effected by a validation of the sterilization process used. Here, it is scientifically proven that a sterilization process carried out with particular parameters always achieves the desired result. Here, the desired result is defined via the factor by which a germ load in the medical device is reduced by the sterilization process. An effective sterilization can be regarded as having been effected e.g. when the germ load has been reduced by a factor of 10¹².

A current process for determining the effectiveness of a sterilization process consists of introducing a sample which is provided with a known germ load at a critical point of a medical device. A critical point here denotes a point of the medical device at which a particularly small effect of the sterilization process is expected, for example because the point heats up particularly slowly, or because it is particularly difficult for media used for the sterilization to reach.

The medical device is then subjected to the sterilization process. The sample is then removed and the remaining germ load is determined.

Paper strips, which are inoculated with particularly temperature-stable germs, for example with Geobacillus stearothermophilus, are often used as samples.

If the evaluation of the sample reveals that the necessary reduction of the germ load has been achieved, the sterilization process is regarded as reliable and is validated.

While the described method is widely recognized, it does to some extent have substantial disadvantages. Firstly, the evaluation of the samples requires a substantial outlay on equipment and time, as an incubation in a culture medium lasting several days is required first before an evaluation of the remaining germs, in order to arrive again at a germ density to be evaluated meaningfully. Secondly, the introduction of the samples into the medical device to be sterilized is often difficult. If, for example, the medical device has a sealed volume, this may have to be opened in order to introduce the sample. The results of the validation can also be distorted thereby. In addition, it can happen that a critical point of the medical device is difficult for the sample to reach or cannot be reached by it at all, for example if the medical device comprises thin channels or tubes. A further disruptive effect consists of a sample influencing the concentration of a medium used in the sterilization process, for example in that a paper strip absorbs water and thus reduces the humidity in its surroundings.

From the patent applications WO 00/27228 A1 and WO 00/27229 A1 processes are known for computationally determining the reduction of a germ load achieved at a critical point of a food product during a thermal sterilization. For this, however, only the temperature profile at a so-called “Cold Spot” of the product is simulated, the dependence on other media is not taken into account.

In particular in the case of sterilization processes in which more than one medium is used, these processes are inadequate.

An object of the invention is thus to provide a process for determining the effectiveness of a sterilization process for a medical device in a sterilizer which is improved with respect to the described problems.

A further object of the invention is to provide an improved process for validating a sterilization process for medical devices.

One or more of the named objects are achieved according to a first aspect of the invention by a process for determining the effectiveness of a sterilization process for a medical device in a sterilizer, with the steps of: providing a data structure, wherein the data structure represents a grid formed of a plurality of three-dimensional cells, recreating the medical device arranged in the sterilizer in the data structure in such a way that a first plurality of cells of the grid represent a body of the medical device and that a second plurality of cells represent an interior of the sterilizer which is not occupied by the body of the medical device, recreating an initial state in the data structure in such a way that each cell of the second plurality of cells is assigned data with respect to the temperature prevailing at the location of the cell, the quantity of a first medium located in the area of the cell and the quantity of a second medium located in the area of the cell, recreating, step by step, changes in the temperature, the quantity of the first medium and the quantity of the second medium occurring in each cell of the second plurality of cells during the sterilization process, calculating a reduction of a germ load achieved in each cell of the second plurality of cells during the sterilization process taking into account the prevailing temperature, quantity of the first medium and quantity of the second medium in the respective cell in each step.

It has surprisingly been found that with processes known from computational fluid dynamics, in which a continuous space is divided into discrete cells in which constant relationships are assumed in each case, not only can flows of media be recreated well, but with it a current and an accumulated reduction of the germ load can also be calculated with a high degree of precision for each location of the medical device, even if there is a complex geometry.

In the case of the recreation of sterilization processes with more than one medium, the quantity of the individual media in each cell of the data structure is important for several reasons.

Firstly, the individual media can have a substantial influence on the heat transfer between the individual cells, e.g. on the heat transfer between the interior of the sterilizer and the body of the medical device. Interior of the sterilizer here denotes the total free interior which is not filled by solid constituents of the medical device. Therefore, this also includes internal cavities of the medical device.

Secondly, the quantity of the individual media can also have a direct influence on the reduction of the germ load.

In general, the temporal progression of the germ load N at one point of the medical device can be described with the following differential equation:

$\frac{\mathrm{dN}}{\mathrm{dt}}=-k*N$

Here, k is the so-called deactivation rate, which indicates what proportion of the germ population is deactivated or killed in an infinitesimally short time interval dt. Firstly, the deactivation rate is strongly dependent on the temperature, wherein the deactivation rate rises approximately exponentially with the temperature. Secondly, the deactivation rate is also dependent on the heat transfer from the medium surrounding a germ to the germ itself. For example, at the same temperature a much higher deactivation rate can thus result if there is a high proportion of water vapour in the atmosphere than if the air is dry. Of course, the quantity or concentration of directly active media such as ethylene oxide also has a direct influence on the deactivation rate k.

For the computational recreation, the above-named differential equation is replaced by a finite difference equation which, with discrete time intervals Δt, calculates:

$\frac{\Delta N}{\Delta t}=-k*N$

In the case of the above-specified finite difference equation, changes in the germ load due to flow and diffusion are disregarded; these do not play an appreciable role in usual sterilization processes.

Now, in the process according to the invention, it is calculated in many individual steps how the temperature and the quantity of the individual media change in the cell of the grid. Causes for the change in the quantities of media are, for example, flow and diffusion processes, but also heat transfer processes such as for example condensation and evaporation. In each step the resultant change in the germ load is then determined for each cell of the grid, with the result that after the recreation of the complete sterilization process the ultimately achieved reduction of the germ load is known for each cell of the grid. The recreation also relates to the edges of the cells and thus optionally the surface of the medical device. The total sterilization process is thus computationally recreated or simulated.

The process according to the invention offers the advantage that the effectiveness of a sterilization process for a particular medical device can be determined without this process having to be actually carried out, and without samples then having to be evaluated in a laborious manner. It thereby becomes possible to determine the effects of changes on the effectiveness of the process. Here, both design changes of the medical device and parameter changes of the sterilization process can be simulated. In this way both the medical device and the sterilization process can be optimized with respect to the use of material and energy.

Furthermore the process according to the invention offers the advantage that points of a medical device which are not accessible to samples can also be taken into account in the determination of the effectiveness of a sterilization process.

In a development of a process according to the invention the quantity of a third medium can additionally be taken into account in each cell.

For example, ethylene oxide or hydrogen peroxide, which are used in gas or plasma sterilization, can be taken into account as the third medium. The quantity of these media in each cell has a direct influence on the respective deactivation rate.

According to a particular development, a phase transition of the first, second and/or third medium can be taken into account in the recreation of the sterilization process.

Thus, for example, a medical device can be provided with a water load before the sterilization in the autoclave, in order to provide sufficient water vapour for the actual sterilization procedure. For this, a medical device or a gas-filled component of the medical device can be exposed to a vacuum first in a pre-treatment, with the result that air is sucked out of the medical device, and then an “aeration” with water vapour can be effected. The water vapour then penetrates into the medical device and in a large part condenses to water droplets on the surface of the medical device.

These water droplets have to be evaporated first in the actual sterilization process, which has a great influence on the temperature and media distribution during the sterilization process. By taking this phase transition into account, the recreation of the process becomes even more precise.

According to a further design of a process according to the invention a shape change of the medical device can additionally be taken into account in the recreation of the sterilization process. For this, the cells of the grid which represent the medical device can be assigned values for the elastic and/or plastic behaviour of the respective material.

If now, for example, a water reserve evaporates during the sterilization process in an interior of a flexible medical device, such as a blood, serum or dialysis bag, then the medical device can swell, whereby the flow and diffusion processes are substantially influenced. Taking this deformation into account results in an even more precise recreation of the sterilization process.

In an additional development of a process according to the invention a diffusion of the first, second and/or third medium through the material of the medical device can be taken into account in the recreation of the sterilization process.

A diffusion of media can be intentional or even necessary. Thus, for example, in the case of ethylene oxide sterilization of packaged medical devices the ethylene oxide must diffuse through the packaging in order to reach the actual medical device. Within the meaning of the invention the packaging here is to be understood as a constituent of the medical device. However, an unintentional diffusion can also have an appreciable influence on the effectiveness of the sterilization process. On the whole, the validity of the recreation can be increased even further by taking the diffusion into account.

As a rule air is to be taken into account as the first medium. Water, which can be present both as a liquid and as water vapour, is usually to be taken into account as the second medium. Ethylene oxide or hydrogen peroxide comes into consideration as the third medium or, in the absence of water, as the second medium.

One or more of the above-named objects are achieved according to a second aspect of the invention by a process for validating a sterilization process for medical devices, with the steps of: defining a reduction of a germ load to be achieved by the sterilization process; carrying out a process according to the first aspect of the invention; comparing the reduction of the germ load determined in each cell of the second plurality of cells; and grading the sterilization process as effective if the necessary reduction of the germ load has been achieved for each of the cells, or grading the sterilization process as not effective if the necessary reduction of the germ load has not been achieved for at least one of the cells.

The described process greatly simplifies the validation of a sterilization process as the introduction of samples and the subsequent evaluation of the samples can be dispensed with. As the validation of a sterilization process for a particular medical device is a prerequisite in many legal systems for the approval both of the sterilization process and of the medical device itself, the approval of new medical devices can be simplified and accelerated, with the result that new and innovative medical devices can be put on the market, and thus benefit patients, more quickly.

In a further development of the process according to the invention for validating a sterilization process, a checking process can additionally be carried out, with the steps of: introducing a sample provided with a known germ load at a predefined point of a medical device to be sterilized, carrying out the sterilization process to be validated on the medical device, determining the reduction of the germ load of the sample achieved by the sterilization process, and grading the sterilization process as effective only when the reduction of the germ load of the sample actually achieved corresponds sufficiently precisely to the reduction of the germ load calculated for the corresponding point.

Even though the positioning and subsequent evaluation of a sample is necessary for the validation according to the described further development, the process is advantageous compared with the validation according to the state of the art. Thus, for example, it can be proved by the simulation that the location at which the sample was introduced is actually a critical location of the medical device, thus a location at which the sterilization process brings about the smallest reduction of the germ load. Even if the critical location of the medical device cannot be reached by a sample, it can be proved with the described process that the result of the simulation at the location at which the sample was introduced matches the actual result of the sterilization process. It can then be assumed that the simulation result is also correct for the actually critical location.

One or more of the named objects are achieved according to a third aspect of the invention by a data processing system, comprising at least one processor, a memory, input means and output means, and which is developed in that program code information which, when executed by the processor, is able to prompt the latter to execute a process according to the above descriptions is stored in the memory.

The data processing system can comprise a computer customary in the trade, which is expediently equipped for the CPU-intensive process with one or more powerful processors and enough RAM.

The input means can, in addition to usual input means such as keyboard, mouse, touchscreen etc., also comprise an interface with a network, via which the data processing system is connected to a database in which information about geometric and material-typical properties of one or more medical devices is stored.

The output means can, in addition to usual output means such as monitor and/or printer, also comprise a storage medium, on which the results of the described processes are stored as data. These data can comprise tables, in which the results are represented numerically. The data can also comprise images and/or videos, by which the progression or the result of the described processes is visualized.

The program code information can be stored in the form of an executable computer program on a storage medium of the computer, for example on a hard drive.

One or more of the named objects are achieved according to a fourth aspect of the invention by a computer program product, comprising a data carrier and program code information stored on the data carrier which, when executed by a processor, is able to prompt the latter to execute a process such as described previously.

One or more of the named objects are achieved according to a fifth aspect of the invention by a sterilized medical device, which has been subjected to a sterilization process, the effectivity of which has been determined by a method as described above, or which has been validated by a method as described above.

One or more of the named objects are achieved according to a sixth aspect of the invention by a medical device, which has been produced in a sterilizer, wherein the effectivity of a sterilizing method used in the sterilizer has been determined by a method as described above, or which has been validated by a method as described above.

The sterilizer encompasses all means required for executing the respective sterilizing method. By example, the sterilizer shall encompass means required for aeration with water vapour, and also an autoclave chamber.

The invention is explained in more detail below with the aid of some exemplary representations. The embodiment examples represented are to serve merely for the better understanding of the invention, without limiting it.

There are shown in:

FIG. 1: a medical device,

FIG. 2: a sterilizer for a medical device,

FIG. 3a: a sectional representation of the medical device according to FIG. 1,

FIG. 3b: a section of FIG. 3a with a grid structure,

FIGS. 4a-4c: possible visualizations of a simulation result,

FIG. 5: a data processing system.

FIG. 1 shows a medical device, in the example represented it is a bag set 1 for peritoneal dialysis.

In peritoneal dialysis a dialysis fluid is introduced into the patient's abdominal cavity via a catheter in the abdominal wall. Via the extensive contact of the dialysis fluid with the peritoneum, which surrounds all the organs located in the abdominal cavity, harmful substances are flushed out of the patient's blood into the dialysis fluid, and thus removed from the blood. After a certain residence time, which is as a rule approximately four hours, the dialysis fluid loaded with harmful substances, the so-called dialysate, is drained off from the patient's abdomen and replaced by fresh dialysis fluid.

The bag set 1 comprises a solution bag 2, which has two chambers 3, 4 filled with dialysis fluid, as well as a technically required empty chamber 5. The empty chamber 5 is also called the lambda chamber because of its shape. Each of the chambers 3, 4, 5 is provided with a connecting piece. Two components of a dialysis solution, a glucose solution and a buffer solution for regulating the pH of the final dialysis solution are stored in the chambers 3, 4. The glucose solution and the buffer solution are not mixed until they are used, thus not until immediately before introduction into the patient's abdominal cavity.

Furthermore, the bag set 1 comprises an empty drainage bag 10, which is provided with two connecting pieces. The drainage bag 10 has a single receiving chamber 11, not visible in FIG. 1, for dialysate. In order to make it easier to run the dialysate into the drainage bag 10, the latter can be equipped with stiffening rods, not represented.

A central connector 15 of the bag set 1 serves to connect the bag set to the patient's catheter. The central connector 15 is connected to the solution bag 2 and to the drainage bag 10 via tubes 16, 17. Either the solution bag 2 or the drainage bag 10 can be connected to the catheter via a valve, not represented.

The tube 16 connects the central connector 15 to the solution bag 2. In the packaged state, the tube 16 is rolled up spirally, it is therefore also called a solution coil. At this stage the tube 16 is connected to the connecting piece of the solution bag 2, which opens into the empty chamber 5.

Not until immediately before the use of the bag set 1 is the tube 16 connected to the chambers 3 and 4 previously separated from each other, in order to guide the now mixed solutions to the central connector 15.

The tube 17 connects the central connector 15 to one of the connecting pieces of the drainage bag 10. A second connecting piece can be provided for example in order to gain access to the drainage bag with the aid of a syringe. Then, for example, a test for analysis of the dialysate can be performed. The tube 17 is likewise rolled up in the packaged state and is called a drainage coil.

The individual components of the bag set 1 are subjected to a pre-treatment before being assembled, in order to deposit water in all air-filled spaces for the later sterilization procedure.

For this, the components are positioned in a vacuum chamber. This chamber is then evacuated to a pressure of for example between 150 hpa and 300 hpa residual pressure and then, for example with the aid of a steam nozzle, flooded abruptly with water vapour, for example to a pressure of approximately 1450 hpa. In the process the vapour penetrates into the cavities of the components of the medical device and condenses to water droplets. This pre-treatment is called steaming.

The bag set 1 is then assembled and shrink-wrapped in a plastic bag, not represented, for storage and for transport.

The finally packaged bag set 1 must be sterilized before use, in order to avoid an infection of the patient. For this, as a rule several bag sets are introduced into a sterilizer, which is represented in FIG. 2.

FIG. 2 shows a sterilizer for medical devices which is an autoclave 20. The autoclave has a sterilization chamber 21, in which in the example represented 24 packaged bag sets 1 are arranged on suitable mesh racks. The sterilization chamber 21 can be closed in a pressure-resistant manner by a door, not represented.

During the sterilization process the sterilization chamber 21 is exposed to superheated steam at high pressure. For example a pressure of 2600 hpa and a temperature of approximately 130° C. can be achieved here.

Due to the combination of high pressure and high temperature germs present in the bag system 1 are killed, with the result that they can no longer cause an infection of the patient.

The effectiveness of the sterilization process depends on various parameters. In addition to the pressure and temperature in the sterilization chamber 21 and the treatment duration, these also include the temperatures actually achieved in the medical device as well as the quantities of water available in the cavities, their evaporation rate and the resultant water vapour concentrations.

According to a conventional method for determining the effectiveness of a sterilization process for medical devices one or more models of the medical device to be sterilized are provided with samples which have a known loading with test germs. As a rule particularly temperature-stable germs are used as test germs, for example of the species Geobacillus stearothermophilus.

The models equipped in this way are then subjected to the sterilization process in question, and then the effect of the sterilization process on the samples is determined. For this, they are incubated in a culture medium over several days and the population of the test germs is evaluated.

In order to reduce the outlay associated with the conventional method, a method is proposed here for determining the effectiveness of the sterilization process by means of a simulation. For this, the medical device and the interior of the sterilizer are recreated in a three-dimensional grid. This is represented schematically in FIGS. 3a and 3b.

FIG. 3a shows a section through the bag set 1 along a plane which runs through the line A-A′ (FIG. 1) and runs perpendicular to the plane of extension of the bags 2, 10. It is recognizable that the solution bag 2 is formed of a lower film ply 30 and an upper film ply 31, which are connected along connection lines 32, 33, 34, 35 such that the chambers 3, 4 for the dialysis solutions and the lambda chamber 5 form.

The drainage bag 10 likewise consists of a lower film ply 40 and an upper film ply 41, which are connected along connection lines 42, 43 such that the receiving chamber 11 forms.

At the connection lines 32, 33, 34, 35, 42, 43 the respective film plies 30, 31, 40, 41 can be glued, heat-sealed, or otherwise connected to each other such that a substantially gas- and liquid-tight connection results.

In FIG. 3b an enlargement of a section X from FIG. 3a is represented, which represents the lower film ply 30 and the upper film ply 31 of the solution bag 2 in the area of the lambda chamber 5. In addition, a three-dimensional grid 100 is represented here, which serves to recreate the bag set 1 in a data structure.

Although the grid 100 in FIG. 3b is represented two-dimensionally for the sake of clarity, it is actually a three-dimensional grid consisting of a plurality of grid cells Z. In the example represented all the cells Z of the grid are the same size and shape, for example tetrahedrons. Depending on the complexity of the shape of the medical device, individual ones of the cells can also have a different shape and/or size.

For each of the cells Z it is defined whether there is a physical constituent of the medical device, such as the film plies 30, 31 of the solution bag 2 at the locations of the cells Z₁, Z₂, at the corresponding point, or whether it is a cell in a cavity or in the surroundings of the medical device, such as the cells Z₃, Z₄.

For each cell Z of the grid 100 a dataset is provided in the data structure.

For the cells which are filled by physical constituents of the medical device, the dataset contains the prevailing temperature as well as material data of the medical device, such as the elastic properties of the material, the heat capacity, the thermal conductivity, as well as the permeability for different media (air, water, steam, etc.). For the other cells, the dataset contains the quantities of the media present in the respective cell (air, water, water vapour, etc.) as well as data about their thermodynamic state (temperature, pressure, flow rate and direction, etc.). Additionally, for each cell representing a cavity an item of information with respect to a germ load or an achieved reduction of the germ load is provided.

Boundary surfaces G, which are recognizable as lines in FIG. 3b, are formed between neighbouring cells Z.

The data structure is then filled with data, so that it represents an initial state at the start of the sterilization process. For example, approximately room temperature will be present in all the cells, and the pressure is approximately 1000 hpa in each cell which represents a cavity.

At the same time, a mixture of air and water vapour, for example steam or steam-air mixture with approx. 2.6 to 3.6 bar absolute pressure and a temperature of for example 130° C., will be present in all the cells which are located outside the medical device.

In the case of cells which are located in sealed cavities of the medical device, other relationships can result due to the previous steaming. Thus, some cells here are optionally filled with water, while in other cells there is a mixture of air and water vapour and also condensed water, which corresponds to a complete saturation.

For cells in cavities of the medical device filled with fluid, all the cells are correspondingly filled with the respective fluid.

Subsequently it is computationally determined step by step how the relationships in the individual cells Z of the grid change while the sterilization process is being carried out. A time interval recreated by a computation step can be, for example, one second, but longer or shorter time intervals can also be realized.

During a heating phase of the sterilization process the sterilization chamber 21 is supplied with superheated steam, with the result that in some cells, which represent this space, pressure, water vapour quantity and temperature rise. As soon as there are differences between two neighbouring cells, a transfer of energy and/or media through the respective boundary surface between the cells results. The hereby resultant changes of state of the individual cells are determined computationally. The computation methods to be used for this are sufficiently known from computational fluid dynamics and therefore need not be explained in more detail here. The following effects are substantially to be taken into account here:

Temperature equalization: if there is a temperature difference between two neighbouring cells, heat energy is transferred through the boundary surface from the warmer to the colder cell, whereby the temperatures equalize.

Pressure equalization: if there is a pressure difference between two neighbouring cells, some of the media will flow out of the cell with higher pressure through the boundary surface into the cell with lower pressure, with the result that the pressures equalize.

Concentration equalization: if there is a difference in the concentration of a medium between two neighbouring cells, or a difference in the partial pressures of the media, some of the medium will diffuse through the boundary surface into the cell with lower concentration or partial pressure, with the result that the concentrations or partial pressures equalize.

Gravity: if there is a height difference between two cells, some of the media will flow out of the higher cell through the boundary surface into the lower cell.

Natural convection: if there is a difference in density between two neighbouring cells, this results in a natural convection.

The interaction of pressure equalization, gravity, convection and concentration equalization (diffusion) leads to a height-dependent change in the mixing ratio of gaseous media such as air, water vapour and ethylene oxide. This can have effects on the effectiveness of the sterilization process and therefore has to be recreated computationally as precisely as possible.

After completion of the heating phase the state of the atmosphere in the sterilization chamber 21 is kept constant, with the result that essentially only equalization procedures take place within the medical device. The progression of these equalization procedures is, however, of great importance to the success of the sterilization process, therefore the total duration of the sterilization process is further recreated or simulated according to the above-described method.

A cooling process, in which above all the dialysis solutions present in the solution bag are to be cooled in order to prevent premature degradation, downstream of the sterilization process can on the other hand optionally be excluded.

Further media can be taken into account in the simulation. Thus, for example, a biocidal gas such as ethylene oxide can be introduced into the sterilization chamber and diffuse into the medical device. The corresponding diffusion procedures can be recreated by the simulation process. For example, the injection of ethanol for example into plug-in connections can thus also be readjusted.

The diffusion of media through the material of the medical device can be modelled in the simulation by adding to the data structure data on the absorbency (for example as permeability or diffusion data) of the material for individual media. If, for example, the material can absorb a certain quantity of water vapour, water vapour will diffuse via a boundary surface into the respective cell if the concentration of the water vapour in the neighbouring cell is high enough. Thus, water vapour can disperse in the material slowly cell by cell and even escape again at boundary surfaces to cavities where there is a lower concentration. Thus, for example, water vapour can diffuse from the sterilization chamber through the film plies 30, 31 into the lambda chamber 5. In the same way, the diffusion of other media such as ethylene oxide or ethanol can also be simulated.

During the sterilization process further effects can emerge, which have to be taken into account in the simulation. Thus, for example, in sealed volumes of a medical device an increase in the internal pressure will result. This rise in pressure is particularly relevant when liquid water, which evaporates due to the temperature increase, is present in the corresponding volumes at the start of the sterilization process. The evaporation procedure must be taken into account in the simulation as it has a substantial influence on the heat distribution in the medical device. Likewise, at some points of the medical device condensation can occur, which likewise influences the temperature distribution.

Due to the evaporation of water the lambda chamber 5 or the receiving chamber 11 can furthermore swell, whereby the geometry of the corresponding volumes changes.

Allowances can be made for this effect in different ways. Firstly, the elastic and/or plastic deformability of the material of the medical device can be stored in the data structure. In each computation step it can then be determined whether a force is acting on a cell which represents a physical constituent of the medical device, with the result that it moves. If a movement of the material in the cell is established, either the grid can remain unchanged and the movement can be imaged in that the corresponding state data are assigned to a neighbouring cell into which the material has moved. It can also become necessary for individual cells to have to be added or removed. However, this can have the result that after the shift cells exist which are no longer assigned any state data, which leads to problems.

A better solution is to construct the entire grid dynamically such that the size and position of the individual grid cells can change, in order to allow for such expansion effects. Here, it is to be borne in mind that in areas in which a clear volume change is to be expected a sufficiently fine grid structure is chosen in order that the result does not become imprecise due to grid cells ultimately being too large.

As a decisive part of the simulation, in each computation step for each cell of the grid which does not correspond to a physical constituent of the medical device the effect of the respectively prevailing state on a possible germ population is calculated. During the definition of the initial state each cell can be assigned a particular germ load, for example an occupancy with 10⁶ germs of the species Geobacillus stearothermophilus.

With the aid of the finite difference equation ΔN_i=−k_i*N_i*Δt the alteration of the germ load and the remaining germ load are then determined. In the process the deactivation rate k is determined depending on the respectively present ambient parameters, thus for example the temperature, the water vapour concentration and/or the concentration of active media such as ethylene oxide.

Instead of calculating a notional germ load, in each computation step and for each computation cell a logarithmic germ reduction F can also be determined and then added up in order to determine the germ reduction achieved during the total sterilization process:

$F_i=\log \frac{N_{i+1}}{N_1}=\log \left(1-k_i*\Delta t\right)$ $F_{\mathrm{tot}}=\log \frac{N_{\mathrm{end}}}{N_{\mathrm{start}}}=\Sigma F_i$

The results of the simulation can be represented or visualized in different ways. One possibility is to output the smallest germ reduction achieved in the medical device as a number.

The progression of a parameter of interest over the duration of the sterilization process can be output as a graph for a selected cell.

Further possibilities are to represent selected parameters colour-coded or greyscale-coded in sectional representations of the medical device. Here the state at a particular point in time during the sterilization process can be represented, for example the temperature or the achieved germ reduction after 1000 seconds, after 2000 seconds and at the end of the sterilization process.

In FIGS. 4a to 4c, for example, visualizations of the temperature of the dialysis solutions after a sterilization process are represented. FIG. 4a shows the temperature at the outer surfaces of the solution chambers 3, 4; FIG. 4b shows the temperature in a section parallel to the surface of extension of the solution bag 2; and FIG. 4c shows the temperature in a section perpendicular thereto. It is recognizable that in the example represented a very homogeneous final temperature of the solutions has been achieved.

The progression of the respective parameters over the duration of the sterilization process can also be provided as a video. In similar representations, pressure, water vapour concentration and/or achieved germ reduction can also be represented.

The described simulation process can be used to determine the effectiveness of a sterilization process for a particular medical device, such as for the bag set 1 in the example represented. In this way, e.g. after a design change or redevelopment of a medical device, it can be checked whether a known sterilization process is sufficient to sterilize the medical device reliably. In this way the effects of adjustments on the sterilizability can be tested without the need to manufacture and sterilize sample copies for every adjustment.

Thereby, new or modified medical devices can be made available to the market fast, as the effectivity of a suitable sterilization method can quickly be shown.

Parameter changes in sterilization processes can likewise be tested with the described simulation process for their effects on the result, without having to accept the described outlay for performance and sampling.

In order to test individual components of a medical device with respect to their sterilizability, it can make sense to limit the simulation initially to these components and their immediate surroundings. The necessary computational outlay can thereby be reduced substantially. However, a complete simulation should always be effected for a conclusive assessment.

Finally, it is even conceivable to use the results of the described simulation process to validate a sterilization process for the legal approval of a new or altered medical device or a sterilization process.

For this, a germ reduction to be achieved by the sterilization process is predefined, which is for example a 12-log reduction, thus a germ reduction by a factor of 10¹². It is then checked, with the aid of the simulation, that the required germ reduction is achieved at every point of the medical device. If the required reduction is achieved, the successful sterilization is validated and the medical device can be approved.

The reliability of the proof can be further increased if a sampling with a sample is effected in addition to the simulation and the result of the simulation is compared with the result of the sampling. The approval can then be made dependent on the results matching.

Here, in contrast to the conventional validation process, the sampling can be effected at a point of the medical device which is not a critical point, as only the match with the simulation result needs to be proved. The outlay on the sampling can hereby be reduced. Influences of the sample on the media distribution in the medical device can be taken into account in the simulation or compensated for by a corresponding addition or deduction of media.

In contrast to the conventional validation process, proving the match between simulation and sampling can optionally be effected in an interrupted sterilization process, for example when the actually necessary germ reduction has not yet been achieved. This has the advantage that a larger population of test germs, which can be evaluated more easily, is still present on the sample after the sterilization process.

By the validation process described above, a new or modified medical device can be made available to the market even faster.

In the described simulation process it must be taken into account that the initial state is possibly not identical for every individual medical device. Thus, in particular, the position and/or size of water droplets which enter the medical device due to the steaming can be random and can differ from medical device to medical device. Precisely in the case of medical devices with awkward geometries, for example long tube sections, the position of water droplets in the tube section can have relevant effects on the result of the sterilization process.

It can therefore be necessary to model some possible distributions of the water droplets and to simulate the effects separately. For a validation, the distribution would then have to be based on which one brings the poorest sterilization result.

In order to determine the effect of the steaming of the medical device and a resultant distribution of water droplets in the medical device, a simulation process designed analogously to the above-described simulation process of the sterilization process can likewise be carried out for the steaming process. However, it must be taken into account here on the one hand that the actual position and size are randomly affected strongly by water droplets forming due to condensation, with the result that at best estimates are possible. On the other hand the water droplets can move and merge in the medical device, if the medical device is moved between the steaming and the sterilization.

The described simulation process can be carried out on a data processing system, such as is represented in FIG. 5.

The data processing system 100 comprises a central processing unit 101 with at least one processor 102 and a storage element 103. The at least one processor 102 can be a powerful multi-core processor which is optimized for the execution of complex mathematical tasks. The storage element 103 can comprise writable components (RAM) and non-writable components (ROM). The storage element 103 preferably has a large storage capacity and a high write and read speed.

The central processing unit 101 can be formed by a computer customary in the trade, e.g. a PC.

The central processing unit is connected to input means and output means, via which information about the sterilization process to be simulated can be input and output. The input means can comprise e.g. a keyboard 104 and a mouse 105. The output means can comprise a monitor 106. If the monitor 106 is a touchscreen, it can at the same time also function as input means.

The central processing unit can be connected to a database 111, in which design data for one or more medical devices, one or more sterilizers and/or data for one or more sterilization processes are stored, directly or via a network 110. The processor 102 can access the data stored in the database 111 in order to recreate a medical device and/or a sterilizer in a data structure, and/or in order to recreate a sterilization process by means of the above-described simulation process.

The central processing unit 101 is furthermore connected to a write/read device 112 for the data carrier 113. In the example represented the data carrier 113 is a CD or DVD, alternatively other known removable or non-removable data carriers can be used.

Program code information, which can be transferred into the storage element 103 by the processor 102, can be stored on the data carrier 113. From the storage element 103 the processor 102 can then read and execute this program code information in steps, whereby the processor is prompted to execute the above-described simulation process.

The central processing unit can likewise use the write/read device to store results of the simulation process on a data carrier 113. Alternatively, the results can be visualized on the monitor 106 and/or stored in the database 111.

The representation of the data processing system 100 in FIG. 5 is greatly simplified for a better overview. In particular, the at least one processor 102 in a real data processing system is not connected to the peripheral devices 104, 105, 106, 112 directly, but via suitable interface elements.

Claims

1. A process for determining the effectiveness of a sterilization process for a medical device in a sterilizer, with the steps of

providing a data structure, wherein the data structure represents a grid formed of a plurality of three-dimensional cells,

recreating the medical device arranged in the sterilizer in the data structure in such a way that a first plurality of cells of the grid represent a body of the medical device and that a second plurality of cells represent an interior of the sterilizer which is not occupied by the body of the medical device,

recreating an initial state in the data structure in such a way that each cell of the second plurality of cells is assigned data with respect to the temperature prevailing at the location of the cell, the quantity of a first medium located in the area of the cell and the quantity of a second medium located in the area of the cell, recreating, step by step, changes in the temperature, the quantity of the first medium and the quantity of the second medium occurring in each cell of the second plurality of cells during the sterilization process,

calculating a reduction of a germ load achieved in each cell of the second plurality of cells during the sterilization process taking into account the prevailing temperature, quantity of the first medium and quantity of the second medium in the respective cell in each step.

2. The process according to claim 1, wherein a quantity of a third medium present in each cell (Z) of the second plurality of cells is additionally taken into account.

3. The process according to claim 1, wherein a phase transition of the first, second and/or third medium is taken into account for the recreation of the sterilization process.

4. The process according to claim 1, wherein a shape change of the medical device is taken into account for the recreation of the sterilization process.

5. The process according to claim 1, wherein a diffusion of the first, second and/or third medium through the material of the medical device is taken into account for the recreation of the sterilization process.

6. The process according to claim 1, wherein the first medium is air.

7. The process according to claim 1, wherein the second medium is water.

8. The process according to claim 1, wherein the second or the third medium is ethylene oxide.

9. A process for validating a sterilization process for a medical device, with the steps of:

defining a reduction of a germ load to be achieved by the sterilization process;

carrying out the process according to claim 1,

comparing the reduction of the germ load determined in each cell of the second plurality of cells; and

grading the sterilization process as effective if the necessary reduction of the germ load has been achieved for each of the cells, or

grading the sterilization process as not effective if the necessary reduction of the germ load has not been achieved for at least one of the cells.

10. The process according to claim 9, wherein a checking process is additionally carried out, with the steps of:

introducing a sample provided with a known germ load at a predefined point of a medical device to be sterilized,

carrying out the sterilization process to be validated on the medical device, determining the reduction of the germ load of the sample achieved by the sterilization process, and

grading the sterilization process as effective only when the reduction of the germ load of the sample actually achieved corresponds sufficiently precisely to the reduction of the germ load calculated for the corresponding point.

11. A data processing system, comprising wherein program code information which, when executed by the processor, is able to prompt the latter to execute the process according to claim 1 is stored in the memory.

at least one processor,

a memory,

input means and

output means,

12. A computer program product, comprising a data carrier and program code information stored on the data carrier which, when executed by a processor, is able to prompt the latter to execute the process according to claim 1.

13. A sterilized medical device, wherein the medical device has been subjected to a sterilization process, the effectivity of which has been determined by the process of claim 1.

14. A sterilized medical device, wherein the medical device has been subjected to a sterilization process, which has been validated by the process of claim 9.

15. A sterilized medical device, wherein the medical device has been produced in a sterilizer, wherein the effectivity of a sterilization method used in the sterilizer has been determined in the process of claim 1.

16. A sterilized medical device, wherein the medical device has been produced in a sterilizer, wherein the effectivity of a sterilization method used in the sterilizer has been validated by the process of claim 9.