阅读说明：本技术 具有带标记元件的主体的容器及其制造方法 (Container having a body with a marking element and method for manufacturing the same ) 是由 O·苏赫 B·汉兹格尔 F·毛瑞尔 P·托马斯 于 2020-11-03 设计创作，主要内容包括：本发明涉及用于盛放至少一种药物组合物的容器,该容器具有携带至少一个标记元件的主体,同时还涉及一种制造容器的方法,优选地是制造根据本发明的容器的方法。(The present invention relates to a container for containing at least one pharmaceutical composition, the container having a body carrying at least one marking element, and to a method of manufacturing a container, preferably a container according to the present invention.)

1. A container for holding at least one pharmaceutical composition,

the container is provided with a main body and a plurality of grooves,

wherein the body comprises at least one marking element at least one location usable to identify the container;

wherein a value of at least one stress parameter of the body at the location is less than or equal to at least one threshold value;

wherein the threshold value is derived and/or obtainable from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one surface and/or volume region of the body with or without the marking element;

wherein at least one mean value is obtained or obtainable by said simulation of said stress parameter for at least a portion of said surface and/or volume region of said body;

wherein the threshold is the sum of the average and 1000% or less of the absolute value of the average.

2. The container of claim 1, wherein

The stress parameter is at least one parameter of the group consisting of: a first principal stress, a mechanically induced tensile stress, a mechanically induced compressive stress, a thermally generated stress, and/or a chemically generated stress;

preferably, the first and second electrodes are formed of a metal,

the mechanically induced tensile stress is a mechanically induced tensile stress during use;

the mechanically induced compressive stress is a mechanically induced compressive stress during use;

the thermally generated stress is a tensile stress and/or a compressive stress, preferably present in the volume and/or the surface of the body; and/or

The chemically generated stress is a tensile stress and/or a compressive stress, preferably present in the volume and/or the surface of the body.

3. The container according to any one of the preceding claims,

wherein the value of the stress parameter of the body at the location is less than or equal to the threshold value under at least one condition of state, wherein the simulation is preferably run under the condition of state;

preferably, wherein the status condition comprises:

the ambient pressure of the body is 1 bar; and/or

At least one force is preferably applied radially and/or axially to at least a portion of the body at a limit of the burst strength of the body.

4. The container according to any one of the preceding claims,

wherein (i) the value of each of two or more stress parameters of the body is less than or equal to the respective two or more threshold values, preferably under two or more state conditions that are identical or at least partially different; and/or (ii) the value of the stress parameter of the body is less than or equal to two or more threshold values under two or more state conditions that are at least partially different.

5. A container according to any of the preceding claims, wherein the body

At least partially designed as a hollow body and/or a tubular body;

having at least one closed end, two open ends and/or at least one opening; and/or

Having at least one internal surface that contacts or is capable of contacting a pharmaceutical composition when the container contains the composition; and/or at least one outer surface which is not in contact with the pharmaceutical composition when the container contains the composition, wherein the marker element is positioned to extend across at least a region of the inner and/or outer surface.

6. The container according to any one of the preceding claims,

wherein the marking element is engraved into at least one surface of the body, preferably into the inner and/or outer surface, wherein the marking element is located at the bottom (13) of the body, preferably in the center of the bottom (13), and/or wherein preferably the marking element comprises at least one-dimensional data code, at least one two-dimensional data code and/or at least one three-dimensional data code, preferably by means of which the container can be identified, when projected to at least one 2D plane;

preferably, the first and second electrodes are formed of a metal,

wherein preferably when projected onto at least one 2D plane, the data code comprises a plurality of dot-like elements and/or line-like elements, preferably in the form of at least one matrix code, preferably at least one dot matrix code.

7. The container according to any one of the preceding claims,

wherein the marking element is produced by and/or is capable of being produced by at least one laser ablation technique, at least one etching technique, preferably at least one dry etching technique, at least one lithography technique, at least one sandblasting technique and/or at least one surface modification technique, without first ablating the material with at least one laser and then subjecting it to at least one treatment with a plasma; and/or

Wherein said marking element is readable by at least one camera and/or light, preferably said light is light emitted by at least one laser and/or at least one light emitting diode, preferably said light has a wavelength in the visible, infrared and/or ultraviolet spectrum.

8. The container according to any one of the preceding claims, wherein the container, preferably the body

Comprising a glass and/or at least one polymer material, preferably the glass is a silicate glass such as an aluminosilicate glass and/or a borosilicate glass; and/or

Designed at least partly in the form of a syringe, in the form of a cartridge, in the form of a vial (1a, 1b, 7) and/or in the form of another medicament container, wherein preferably the bottom (13) of the body at least partly has a concave shape, wherein preferably the centre of the osculating circle at least one point of the bottom (13) of the body is arranged on the side opposite to the body with respect to the bottom (13) of the body.

9. The container according to any one of the preceding claims,

wherein a tempering operation is performed at least partially on the body, preferably at the location of the marking element, preferably at a temperature between 300 ℃ and 400 ℃ and/or for 10 minutes to 25 minutes.

10. A method of manufacturing a container for holding at least one pharmaceutical composition, preferably a container according to any one of claims 1-12, the method comprising:

providing at least one body, preferably at least partially hollow and having at least one closed end, two open ends and/or at least one opening; (101)

identifying at least one location on the body at which the body has at least one stress parameter, preferably a value of the stress parameter less than or equal to at least one threshold value under at least one condition;

wherein the threshold value is derived and/or obtainable from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one surface and/or volume region of the body with or without the marking element;

wherein at least one mean value is obtained or obtainable by said simulation of said stress parameter for at least a portion of said surface and/or volume region of said body;

wherein the threshold is the sum of the average and 1000% or less of the absolute value of the average; (103)

-providing at least one marking element at the identified position, which marking element can be used to identify the container (105).

11. The method of claim 10, wherein confirming the location on the subject comprises:

evaluating the simulation result of the subject and identifying at least one region in which the value of the stress parameter is less than the threshold value, preferably the mean value of the stress parameter is less than the threshold value; (103a) and

selecting the location so that the location is at least partially within the identified region (103 b).

12. The method of any of claims 10-11, wherein disposing the marking element comprises:

ablating and/or etching material of at least one surface area of the body at the identified locations, wherein the ablating and/or etching is preferably performed by at least one first laser, at least one etching technique, preferably at least one dry etching technique, at least one lithography technique, at least one blasting technique, at least one surface modification technique, without ablating material with at least one laser and then performing at least one treatment with a plasma; and/or processing at least one volumetric region of the body at the identified position so as to generate a marking element, preferably by means of a first laser, said marking element preferably being a data code, preferably read by means of at least one camera and/or light, preferably emitted by at least one second laser and/or at least one light emitting diode, said light preferably having a wavelength in the visible, infrared and/or ultraviolet spectrum; wherein the first laser preferably:

(i) is a diode-pumped solid DPSS laser, a fiber laser, an ultraviolet laser, a carbon dioxide laser or a flash lamp-pumped solid laser,

(ii) is a pulsed laser, and is characterized by that,

wherein the pulsed laser preferably (a) has a pulse duration of between 100ps and 500ns, preferably 100 ns; (b) has a pulse energy between 1 and 500 muj; (c) having a pulse repetition rate of between 10 and 400 kHz; and/or (d) has an RMS power of between 1 and 100 Watts, preferably 5 Watts, and/or

(iii) Having a wavelength (105a) between 250 and 600nm, preferably 368 nm.

13. The method of any of claims 10 to 12, further comprising:

at least partially tempering the body, preferably at the location of the marking element, preferably at a temperature between 300 ℃ and 400 ℃ and/or for a time between 10 minutes and 25 minutes (107).

Technical Field

The present invention relates to a container for at least one pharmaceutical composition, the body of which has at least one marking element, and to a method of manufacturing a container, preferably a container according to the present invention.

Background

Containers for holding pharmaceutical compositions, such as vials, syringes, cartridges, etc., are well known in the art. Such containers must generally be equipped with means capable of identifying the single container from a plurality of other containers. This is important for the purpose of automated handling of the containers, for example in the filling, routing, storage, scheduling processes, as well as for ensuring the quality of the containers and safety standards which place high demands on the traceability of each container during its use cycle. Usually, the identification means are designed in the form of marking elements which are subsequently used to meet the above requirements.

It is common today to apply a label to each container and to print a unique identification code, such as a bar code, on the label. Another application is to transfer the unique identification code directly to the container by a printing process using ink. Thus, both methods require printing a code. As long as a link is established between a container and a unique identification code, the container can be identified by reading the corresponding unique identification code.

However, in use, sticking labels to a surface or printing codes using a printer is often slow and complicated in use and thus often represents a bottleneck in a production line. Moreover, the size of these printed codes is often limited by the manner in which they are printed and cannot be reduced sufficiently to create the small codes required. Especially for small containers it is difficult or even impossible to provide a large enough area to apply a label thereon. Often, the geometry of the container is complex, which also makes it difficult to label or utilize a printer to place an identification code thereon.

Furthermore, practice has shown that if the container is subjected to water or to other extreme conditions, there is a risk that its label will fall off or that the code printed directly on it by the ink will disappear on further processing or use of the container. In addition, the codes set according to the above-described known techniques also have a general problem of fading with the lapse of time.

These disadvantages result in containers that cannot be identified any more because the label is completely lost or no longer readable, being discarded. This is particularly true in the pharmaceutical field where the use of unidentified substances is not allowed. However, also in this field, in particular, the disposal of the containers comprising the respective compositions is rather expensive. In addition, identifying ambiguous containers may result in system downtime or at least require additional resources. In any event, the use of the conventional marking elements described above may result in increased service costs.

Even more seriously, the disappearance of the unique identification code leads to an erroneous identification of the container and thus to dispensing errors. At worst, this may lead to serious health risks for the patient.

It is well known in the art that information such as marking elements can be engraved directly on the surface of the container, for example by laser ablation or the like. The production process of providing the marking element on the container in the above-described manner is indeed economical and has advantages in terms of durability and reliability. However, glass containers such as vials used in the pharmaceutical industry are typically subjected to loads such as axial and lateral compression during handling, processing and transportation. This requires that the vessel must be strong enough to withstand the typical loads described above. Since engraving the marking elements on the surface represents damage to the container, such marking elements are generally not considered in applications where the container is to be subjected to the above-mentioned loads.

The object of the present invention is to overcome the above-mentioned drawbacks by providing a container with a marking element which on the one hand is easy and inexpensive to manufacture and on the other hand is not only reliable and durable but also free from the risk of failure and is particularly suitable for use with a wide variety of containers having different dimensions and geometries. It is another object of the present invention to provide a method of manufacturing a container having such a marking element.

Disclosure of Invention

According to a first aspect, the present invention solves the above mentioned problems by a container for holding at least one pharmaceutical composition. The container comprises a body comprising at least one marking element at least one location usable for identifying the container, wherein at least one stress parameter of the body at said location has a value less than or equal to at least one threshold value; wherein the threshold value is derived and/or can be derived from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one surface and/or volume region of the body with or without the marking element; wherein at least one mean value is obtained or obtainable by said simulation of stress parameters of at least a part of a surface and/or volume region of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

The present invention is therefore based on the surprising finding that: if the position of the marking element is chosen such that one or more stress parameters at the position of the marking element are limited to a certain threshold value, it is still possible to arrange the marking element on the container, preferably on its body, for example by a technique of material weakening, such as material ablation. Thus, at a position satisfying this criterion, the marking element can be permanently engraved into the container, while still ensuring a high strength of the container, despite damage of the marking element to the structure of the body.

It has also been found that the threshold value can be defined in a generally universally valid manner if it is set on the basis of the simulation result of the stress parameter of the respective container which preferably carries the marking element. This is advantageous in that the inventive concept is applicable to all types of containers, since only a model has to be simulated, even if the geometry, shape, dimensions and materials of these containers are completely different. Therefore, the method is flexible and universal in application.

Indeed, the design of the product is now typically done by means of respective three-dimensional models, so that no additional costs are required to build the respective models to perform the simulation according to the invention. This makes the method more interesting because it can be easily integrated into existing structures.

More specifically, it was surprisingly found that obtaining the mean value of the respective stress parameter by simulation is not only preferable and rather reliable, but can be used to determine a reference value to which the threshold value is referenced.

In general, the marking elements may be provided on the container (preferably on its body) using a preferred marking technique such as laser ablation or etching. These techniques not only make it possible to manufacture very small marking elements, but can even be used for complex geometries without extensive changes to the manufacturing process. This not only allows for a lower cost of manufacturing the container, but also allows for greater design flexibility for the body. This is true because laser machining and like techniques are not limited to any surface geometry used to provide the marking elements.

According to the inventive concept, the marking element can be engraved into the material of the body, so that the marking element is also very durable and thus reliable and free from the risk of failure. For the same reason, there is no problem of fading, peeling or disappearance of the marking member.

Further analysis reveals that the invention is also surprising in that, when the marking element is provided at the identified location by removing material of the body, the load strength of the entire container is not severely lost, and preferably not lost, despite the material being removed. Thus, the stability of the container can be ensured despite the weakening of the material. In other words, the position identified according to the invention does not appear to be sensitive to damage caused by imprinting of the marking element.

The analysis also shows that from a practical point of view, the position confirmed on the basis of the simulation results is always stable, whether the simulation is carried out on model containers with or without marking elements. In other words, based on the inventive concept, if a first simulation performed on a model container without a marking element generates a specific preferred position of the marking element, then a preferred position of the marking element generated on a second simulation performed on a model container with a marking element disposed at the preferred position is also the position.

As is known, any prior art software tool can be used to perform the simulation involved in the method of the invention, which software tool is capable of not only modeling the container to which the marking element is to be applied, but also performing a finite element analysis simulation of this model for the stress parameter under study. For example, the above simulation can be performed using the 2018 commercial finite element analysis software ABAQUS published by Daxon Corporation (DASSAULT Systems Simulia Corporation) on 11/7/2017, the simulation results of which can be further applied or utilized in the context of the present invention.

It is known that the average obtained by the simulation of the corresponding force parameter may be any kind of average suitable, such as an average or a weighted average. Also, it is known that when using finite element analysis, the stress is calculated for each node of the elements of the mesh. Typically, the elements are different sizes (e.g., the grid of penicillin bottles has different sizes at the bottom and heel), so the average of the stresses can be calculated using the "logical element area" weights corresponding to the nodes. Those skilled in the art will appreciate that the "logical element area" may take into account the percentage of surface area allocated to each node. This means that the "logic element area" of the nodes at the edges will be larger compared to the corners of the simulation model, for example.

It will also be clear to those skilled in the art that the "position" of the marker element will have some spatial expanse. Preferably, it can be expanded in two or three dimensions. For example, the location of the marking element may be a specific size of surface area ablated (e.g., by laser ablation techniques or etching, etc.) of the body on which the marking element is disposed. Of course, this position can also be understood as a three-dimensional volume element provided with a marking element, if desired.

Furthermore, it is well known that labels and inks can be a potential source of contamination and can also produce small particles, which are not suitable for use in clean room environments. Therefore, the use of engraved marking elements may also satisfy clean room conditions.

According to an embodiment, alternatively or additionally, preferably, the thickness of the container, preferably the thickness of the bottom of the container, may be between 0.6 mm and 1.7 mm.

According to an embodiment, alternatively or additionally, it is preferred that the marking elements are engraved to a depth of the container surface, preferably to a depth of between 1 and 2 micrometer of the outer surface of the container.

According to an embodiment, alternatively or additionally, it is preferred that the marking element is engraved to a depth of the container surface, preferably to an outer surface of the container, which is less than 10% of the thickness of the container, preferably less than 10% of the maximum thickness of the container bottom.

According to one embodiment, the threshold value may preferably be the sum of the mean and 900% of the absolute value of the mean, be the sum of the mean and 800% of the absolute value of the mean, be the sum of the mean and 700% of the absolute value of the mean, be the sum of the mean and 600% of the absolute value of the mean, be the sum of the mean and 700% of the absolute value of the mean, be the sum of the mean and 400% of the absolute value of the mean, be the sum of the mean and 300% of the absolute value of the mean, be the sum of the mean and 200% of the absolute value of the mean, or be the sum of the mean and 100% of the absolute value of the mean.

According to an embodiment, alternatively or additionally, preferably, the container may be a vial and the average value is or may be obtained by simulating stress parameters of at least a part of: a cylindrical wall portion of the vial, a bottom portion of the vial, and/or a heel portion of the vial.

According to one embodiment, alternatively or additionally, it is preferred that the position of the marking element on the body is partially or completely located within a surface and/or volume area of the body for performing the stress parameter simulation.

According to an embodiment, alternatively or additionally, preferably, the value of the at least one stress parameter of the body at said location is less than or equal to 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20% or 10%, respectively, of the at least one threshold value.

According to one embodiment, it may alternatively or additionally be particularly preferred to combine the following features:

a container for holding at least one pharmaceutical composition, the container comprising a body comprising at least one marking element at least one location that can be used to identify the container, wherein the value of at least one stress parameter of the body at said location is less than or equal to at least one threshold value; wherein the threshold value is derived and/or can be derived from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one surface region of the body with or without the marking element; wherein at least one average value is obtained or obtainable by simulation of a stress parameter of at least a portion of a surface region of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

A container for holding at least one pharmaceutical composition, the container comprising a body comprising at least one marking element at least one location that can be used to identify the container, wherein the value of at least one stress parameter of the body at the location is less than or equal to at least one threshold value; wherein the threshold value is derived from at least one simulation result based on at least one simulation based on a finite element method of stress parameters of at least one surface region of the body with or without the marking element; wherein at least one average value is obtained or obtainable by simulation of a stress parameter of at least a portion of a surface region of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

A container for holding at least one pharmaceutical composition, the container comprising a body comprising at least one marking element at least one location that can be used to identify the container, wherein the value of at least one stress parameter of the body at the location is less than or equal to at least one threshold value; wherein the threshold value is obtainable from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one surface region of the body with or without the marking element; wherein at least one average value is obtained or obtainable by simulation of a stress parameter of at least a portion of a surface region of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

A container for holding at least one pharmaceutical composition, the container comprising a body comprising at least one marking element at least one location that can be used to identify the container, wherein the value of at least one stress parameter of the body at the location is less than or equal to at least one threshold value; wherein the threshold value is derived and/or can be derived from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one volumetric region of the body with or without the marking element; wherein at least one mean value is obtained or obtainable by simulation of a stress parameter for a volumetric region of at least a portion of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

A container for holding at least one pharmaceutical composition, the container comprising a body comprising at least one marking element at least one location that can be used to identify the container, wherein the value of at least one stress parameter of the body at the location is less than or equal to at least one threshold value; wherein the threshold value is derived from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one volumetric region of the body with or without the marker element; wherein at least one mean value is obtained or obtainable by simulation of a stress parameter for a volumetric region of at least a portion of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

A container for holding at least one pharmaceutical composition, the container comprising a body comprising at least one marking element at least one location that can be used to identify the container, wherein the value of at least one stress parameter of the body at the location is less than or equal to at least one threshold value; wherein the threshold value is obtainable from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one volumetric region of the body with or without the marker element; wherein at least one mean value is obtained or obtainable by simulation of a stress parameter for a volumetric region of at least a portion of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

According to a second aspect, the present invention solves the above mentioned problems by a container for containing at least one pharmaceutical composition. The container comprises a body, wherein the body comprises at least one marking element capable of identifying the container at least one location, wherein the value of at least one stress parameter of the body at the location is less than or equal to at least one threshold value; and wherein the threshold is a fixed value less than or equal to 300 MPa.

The present invention is further based on the surprising finding that: if the position of the marking element is chosen such that one or more stress parameters at the position of the marking element are limited to a certain threshold value, the marking element may be provided on the container, preferably on its body, for example by a technique of weakening the material by ablation of the material or the like. Thus, at a position satisfying this criterion, the marking element can be permanently engraved into the container, while still ensuring a high strength of the container, despite damage of the marking element to the structure of the body.

Furthermore, it has also been found that setting the threshold to a fixed value is a beneficial estimate in many practical aspects. The method allows to easily and directly identify the preferred position of the marking element by means of a highly sensitive standard, while the results produced by the method prove to be reliable in practice.

Thus, even without a model of the container or if for other reasons there is no simulation result of the stress parameters, it is still possible to arrange the marking element on the container in a position chosen that does not have a major influence on the stability of the container.

For example, the fixed value may be determined based on empirical values that have proven reliable in the past. In particular, the fixed values are or can be derived from other experiments and/or analyses. For example, the fixed value is or can be derived from a fracture analysis of the container, which is broken by the application of an external force at the location of the marking element.

For example, the fixed value obtained for the first fracture analysis performed on the plurality of sample vessels is between 70MPa and 235 MPa.

For example, the second fracture analysis performed on the plurality of sample vessels results in a fixed value between 80MPa and 280 MPa.

With regard to the further advantages resulting from the selection of the location based on the stress parameter, reference is made to the comments provided above in connection with the first aspect of the invention, which comments apply here as well, mutatis mutandis.

According to a third aspect of the present invention, the above problem is solved by a plurality of first glass containers, wherein each glass container has a body comprising the following body parts:

i) a glass tube having a first end and another end, wherein the glass tube is characterized by a longitudinal axis L_tubeAnd which comprises in the direction from top to bottom:

ia) a top region at the first end of the glass tube, wherein the top region has an outer diameter dt;

ib) a joining zone following the top zone;

ic) a neck region following the junction region, wherein the neck region has an outer diameter dn, and dn < dt;

id) a shoulder region following the neck region;

ie) a body region following the shoulder region and extending to the other end of the glass tube, wherein the thickness of the glass in the body region is 1b, the outer diameter is db, and db > dt; and

(ii) closing the glass bottom of the glass tube at the other end;

wherein at least one marking element is engraved into at least one surface of at least one body portion;

wherein the loads at which 50% of the glass containers in the first plurality of glass containers fail under axial compression or lateral compression in the axial compression test or the lateral compression test described herein are at least 1200N axial compression and at least 900N lateral compression, respectively; wherein the loads at which 50% of the glass containers in the second plurality of glass containers fail under axial compression or lateral compression in the axial compression test or the lateral compression test described herein are at least 1200N axial compression and at least 900N lateral compression, respectively; wherein a glass container in the second plurality of glass containers is identical to a glass container in the first plurality of glass containers except for the absence of a marking element; wherein the number of glass containers included in the first plurality of glass containers is the same as the number of glass containers included in the second plurality of glass containers.

The invention is therefore based on the surprising finding that: if the position of the marking element is chosen such that there is no statistically significant difference between the container with the marking element and the container without the marking element when assessing the likelihood of breakage of the container under a certain predetermined load, the marking element may be provided on the container, preferably on the body thereof, for example by a technique of material weakening by material ablation or the like.

This method allows to provide a marking element for containers without the drawback of producing defective products due to breakage of the container.

The method thus makes it possible to provide a container, preferably a vial, with a marking element which has the same strength and the same rupture characteristics as the same container without the marking element.

In an embodiment of the first and second aspect, alternatively or additionally, preferably, the stress parameter is at least one parameter of the group consisting of: a first principal stress, a mechanically induced tensile stress, a mechanically induced compressive stress, a thermally generated stress, and/or a chemically generated stress.

By selecting mechanically induced tensile stress as stress parameter, a preferred location may be selected such that only mechanically induced tensile stresses below a threshold value are present. This has proved to be advantageous, since, in particular for containers (or bodies) made of glass, the greater the tensile stress, the less stable the container is in the respective region. Therefore, a region where the mechanically induced tensile stress is not more than a specific value is preferable. For example, if the threshold value is 100MPa, then the mechanically induced tensile stress must be in the range of 0 to 100MPa (note that the mechanically induced tensile stress should take a positive value).

By selecting mechanically induced compressive stress as stress parameter, a preferred location may be selected such that only mechanically induced compressive stresses below a threshold value are present. This has proved to be advantageous, since, in particular for containers (or bodies) made of glass, the more negative the compressive stress, the more stable the container is in the respective region. Therefore, a region where the mechanically induced compressive stress is not more than a specific value is preferable. For example, if the threshold value is-50 MPa, the mechanically induced compressive stress in this example must be in the range of-infinity to-50 MPa (note that the mechanically induced compressive stress should take a negative value; and since the threshold value is negative, it ranges from minus infinity MPa to-50 MPa). Typically, the compressive stress of the container is not less than-3000 MPa, -2000MPa or-1000 MPa.

By selecting the first principal stress as a stress parameter, a combined analysis is possible, since depending on the sign the first principal stress at a specific point of the object surface may be either a compressive stress or a tensile stress. Since this first principal stress allows to take into account both stresses, a very practical evaluation can be made. For example, an average value of the first principal stress over a certain surface area may be evaluated. The average value may be used to indicate whether more tensile or compressive stress is present in each region. The more tensile stresses present, the greater the sum of the tensile stresses on the surface area and hence the greater the positive value (or less negative value) of the average, while the more compressive stresses present, the greater the negative value (or less positive value) of the average. This may in turn also be used to determine a threshold, e.g. the smaller the threshold, the smaller the average value. Also, for smaller thresholds, the marking elements may also be engraved deeper into the surface.

If thermally and/or chemically generated stresses are chosen as the respective stress parameter, special handling of the container or the body may be considered. In particular, it should be noted that tempering is beneficial to reduce or eliminate stress after the marking element is disposed on the container.

According to a preferred embodiment, the stress parameters may be mechanically induced tensile stress and mechanically induced compressive stress.

According to an embodiment of the first and second aspect, alternatively or additionally, preferably, (i) the mechanically induced tensile stress is a mechanically induced tensile stress during use; (ii) mechanically induced compressive stress is mechanically induced compressive stress during use; (iii) the thermally generated stress is a tensile stress and/or a compressive stress, which is preferably present in the volume and/or the surface of the body; and/or (iv) the chemically generated stress is a tensile stress and/or a compressive stress, which is preferably present in the volume and/or the surface of the body.

This allows defining the stress parameters such that the actual conditions are taken into account. This means, for example, during use (with respect to mechanically induced stresses) or at the respective location where stresses occur (with respect to the stresses generated). This in turn allows for more accurate analysis to be performed, thus confirming a more reliable location for placement of the marking element.

According to one embodiment, alternatively or additionally, the following features may be combined, preferably: mechanically induced tensile stress is mechanically induced tensile stress during use; mechanically induced compressive stress is mechanically induced compressive stress during use; the thermally generated stress is a tensile stress, which is preferably present in the volume of the body; the thermally generated stress is a tensile stress, which is preferably present at the surface of the body; the thermally generated stress is a compressive stress, which is preferably present in the volume of the body; the thermally generated stress is a compressive stress, which is preferably present at the surface of the body; the chemically-generated stress is a tensile stress, which is preferably present in the volume of the body; the chemically generated stress is a tensile stress, which is preferably present at the surface of the body; the chemically generated stress is a compressive stress, which is preferably present in the volume of the body; and/or the chemically generated stress is a compressive stress, which is preferably present at the surface of the body.

According to a preferred embodiment, the mechanically induced tensile stress is a mechanically induced tensile stress during use and the mechanically induced compressive stress is a mechanically induced compressive stress during use.

According to an embodiment of the first, second and third aspect, alternatively or additionally, it is preferred that the value of the stress parameter of the body at said location is less than or equal to a threshold value in at least one state condition, wherein preferably the simulation is performed in that state condition.

By setting certain environmental variables to specific values, the force parameters can be analyzed under a more defined framework. The reliability and reproducibility of the stress parameters can thus be improved, so that the recognition position of the marking element is optimized.

According to an embodiment of the first, second and third aspect, alternatively or additionally, preferably the status condition comprises: (1) the ambient pressure of the main body is 1 bar; and/or (2) applying at least one force radially and/or axially to at least a portion of the body, preferably at a limit of body failure strength.

Specifying ambient pressure as a state condition results in a realistic scenario for a variety of applications using the container, and furthermore, it allows for a high degree of reproducibility.

Given that the force is a state condition, the container can be evaluated in a clear scenario. For example, one can consider the extremes before certain events (e.g., breakage of a container) occur. It can thus be ensured that the resulting position is still the preferred position in such extreme conditions.

According to one embodiment, it may alternatively or additionally be particularly preferred to combine the following features:

the state conditions include: the ambient pressure of the main body is 1 bar; the condition comprises applying at least one force radially on at least a portion of the body, preferably at an extreme of the body's burst strength; and/or the condition comprises applying at least one force axially against at least a portion of the body at an extreme of the body's burst strength.

According to a preferred embodiment, the condition is that at least one force is applied axially to the body at a limit of the breaking strength of the body.

In an embodiment of the second aspect, alternatively or additionally, preferably the fixed value is between 50 and 300MPa, preferably between 100 and 200MPa, more preferably 150 MPa.

In different situations, preferably where the load (its value and/or type) applied to the container during use is different, the fixed value may be adapted to more practically reflect the situation.

According to a preferred embodiment, the tensile stress is fixed at 150MPa and the compressive stress is fixed at-500 MPa.

According to an embodiment of the first, second and third aspect, alternatively or additionally, preferably (i) the value of each of the two or more stress parameters of the body is less than or equal to the respective two or more threshold values, preferably under two or more state conditions that are identical or at least partially different; and/or (ii) the value of the stress parameter of the body is less than or equal to two or more threshold values under two or more state conditions that are at least partially different.

Thus, the position of the marking element can be confirmed not only on the basis of a single stress parameter, but also on the basis of two or more stress parameters. For example, mechanically induced tensile stress may be used as the first stress parameter and mechanically induced compressive stress as the second stress parameter. In this case, two identical or different threshold values may also be set. For example, a first threshold for a first stress parameter and a second threshold for a second stress parameter may be specified, where for example the second threshold may be less than the first threshold (e.g., the second threshold is a negative value, such as-50 MPa, while the first threshold is a positive value, such as +100 MPa).

If a condition is specified, it is also applied to the condition, mutatis mutandis. For example, the first and second stress parameters may be observed under the same state conditions, or under different states.

Accordingly, more than two stress parameters may be specified that have one or more thresholds and no or one or more different state conditions.

It is well known that, of course, only tensile or compressive stresses exist at a single point on the surface of an object. For example, it may be determined whether the first principal stress at each point has a positive or negative value, corresponding to a tensile or compressive stress at that point, respectively, by evaluating the first principal stress. However, according to the invention, it is also possible to specify only a single stress parameter, which parameter provides, for example, a value for tensile stress only or for compressive stress only. For example, the value of a single stress parameter corresponding to the tensile stress may be obtained by retaining only positive and zero values of the first principal stress, while discarding negative values. Thus, the point on the surface that is subjected to compressive stress will not contribute to the evaluation of this single stress parameter. Also, such a single stress parameter may be used as the first or second stress parameter discussed above.

Where more than one state condition is utilized, those skilled in the art will appreciate that a corresponding number of simulations may also be included. In some cases, multiple stress parameters under the same state condition need only be simulated once.

The method in each case belongs to a highly flexible method which can take into account a number of different aspects in the present case while also benefiting from the general inventive concept of the present invention.

According to a preferred embodiment, the first stress parameter is a tensile stress and the second stress parameter is a compressive stress under the same conditions of axial load applied to the container at the limit of breakage. A single simulation may be performed under this state condition to obtain first and second thresholds for the first and second stress parameters, respectively.

According to an embodiment of the first, second and third aspect, alternatively or additionally, preferably, the body (i) is at least partially designed as a hollow body and/or a tubular body; (ii) having at least one closed end, two open ends and/or at least one opening; and/or (iii) has at least one internal surface that contacts or is capable of contacting the pharmaceutical composition when the container contains the composition; and/or the body has at least one outer surface which is not in contact with the pharmaceutical composition when the container contains the composition, wherein the location of the marking element extends across at least a region of the inner and/or outer surface.

The manufacture and reading of the marker elements is also facilitated if the location of the marker elements extends across the inner and/or outer surface, since the surface can be written and read directly.

According to one embodiment, it may alternatively or additionally be particularly preferred to combine the following features:

the body is designed as an at least partially hollow body; the body is designed as an at least partially tubular body; the body having at least one closed end; the body has two open ends; the body having at least one opening; the body having at least one inner surface which is in contact with the pharmaceutical composition when the container contains the pharmaceutical composition, and at least one outer surface which is not in contact with the composition when the container contains the pharmaceutical composition, wherein the location of the marking element extends across at least a region of the inner and/or outer surface; the body having at least one interior surface that contacts the pharmaceutical composition when the container contains the composition, wherein the location of the marking element extends across at least a region of the interior surface; the body having at least one outer surface that is not in contact with the pharmaceutical composition when the container contains the composition, wherein the location of the marking element extends across at least a region of the outer surface; the body having at least one inner surface capable of being contacted by the pharmaceutical composition when the container holds the pharmaceutical composition, and at least one outer surface not contacted by the composition when the container holds the pharmaceutical composition, wherein the marking element is positioned to extend across at least a region of the inner and/or outer surface; the body having at least one interior surface capable of contacting the pharmaceutical composition when the container contains the composition, wherein the marking element is positioned in at least one region of the interior surface; and/or the body has at least one outer surface which is not in contact with the pharmaceutical composition when the container contains the composition, wherein the location of the marking element extends across at least a region of the outer surface.

According to a preferred embodiment, the body is designed as a hollow tubular body with at least one closed end and at least one opening, for example a vial of penicillin. According to a preferred embodiment, the marking element is provided on the outer surface. According to a preferred embodiment, the body has two open ends, for example for a syringe.

According to an embodiment of the first, second and third aspect, alternatively or additionally, it is preferred that the body has at least one wall, preferably at least partially enclosed between the inner and outer surface, wherein the position of the marking element extends at least partially across at least one volumetric region within the wall.

According to one embodiment, the body comprises the following body parts:

(i) a glass tube having a first end and another end, wherein the glass tube is characterized by a longitudinal axis L_tubeAnd which comprises in the direction from top to bottom:

ia) a top region at the first end of the glass tube, wherein the top region has an outer diameter dt;

ib) a joining zone following the top zone;

ic) a neck region following the junction region, wherein the neck region has an outer diameter dn, and dn < dt;

id) a shoulder region following the neck region; and

ie) a body region following the shoulder region and extending to the other end of the glass tube, wherein the body region has a glass thickness of lb, an outer diameter of db, and db > dt;

(ii) the glass bottom of the glass tube is closed at the other end.

If the marker element extends across a volumetric region within the wall portion, the marker element may be further protected from damage due to handling or other effects, preferably mechanical damage, thereby making the marker element more durable.

According to an embodiment of the first, second and third aspect, alternatively or additionally, it is preferred that the extension of the projected marking element, preferably when projected to at least one 2D plane, is smaller in at least one dimension, preferably in two or three dimensions, than the largest dimension of the container in the respective one or more directions and/or the largest dimension of the container as a whole, wherein preferably a marking element is indicated to be small in size if its size is not larger than 0.8 or 2 mm, or smaller than 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 3%, 1%, 0.1%, 0.01% and/or 0.001% of the compared size, respectively.

The small size of the marking element allows the marking element to be provided for those bodies with limited space. The 2D plane may be, for example, a plane parallel to the surface of the body. The projection of the marking element on the 2D plane can be such that it no longer has the third dimension, for example the marking element no longer has the depth dimension. In other words, preferably, the projection of the marking element on the 2D plane enables the evaluation of two dimensions of the marking element which do not extend in the wall thickness direction of the body in which the marking element is arranged.

According to one embodiment, it may alternatively or additionally be particularly preferred to combine the following features:

when projected preferably on at least one 2D plane, the dimension of the marking element in at least one dimension, preferably in two or three dimensions, is smaller than the largest dimension of the container in the respective direction or directions, wherein preferably a marking element is small in size if its dimension is not larger than 0.8 or 2 mm; when projected preferably on at least one 2D plane, the dimension of the marking element in at least one dimension, preferably in two or three dimensions, is smaller than the largest dimension of the container in the respective one or more directions, wherein preferably a marking element is small in size if its dimension is smaller than 10%, 5%, 3%, 1%, 0.1%, 0.01% and/or 0.001% of the compared dimension; when projected preferably on at least one 2D plane, the size of the marking element in at least one dimension, preferably in two or three dimensions, is smaller than the overall maximum size of the container, wherein preferably the size of the marking element is small if it is not larger than 0.8 or 2 mm; and/or the size of the marking element in at least one dimension, preferably in two or three dimensions, is smaller than the overall maximum size of the container when projected preferably on at least one 2D plane, wherein preferably a marking element size is small if it is smaller than 10%, 5%, 3%, 1%, 0.1%, 0.01% and/or 0.001% of the compared size.

According to a preferred embodiment, the maximum dimension of the marking element is less than or equal to 2 mm.

According to an embodiment of the first, second and third aspect, alternatively or additionally, it is preferred that the marking element is engraved to at least one surface of the body, preferably to the inner surface and/or the outer surface, wherein the marking element is located at the bottom of the body, preferably in the center of the bottom, and/or wherein the marking element comprises at least one-dimensional data code, at least one two-dimensional data code and/or at least one three-dimensional data code, preferably the data code is usable for identification of the container, when preferably projected on at least one 2D plane.

The engraved marking elements are not only durable but also easy to manufacture, e.g. they may be manufactured by at least one laser and/or laser ablation technique. Preferred types of lasers are Diode Pumped Solid State (DPSS) lasers, fiber lasers or flash lamp Pumped Solid State lasers. In practice, particular preference is also given to UV lasers, which preferably have a wavelength of 250 to 500 nm. Such lasers are suitable for ablation techniques because they are fast, reliable and capable of fabricating small structures. However, lasers with wavelengths between 250 and 600nm may also be preferably used. In certain embodiments, CO may also be employed₂Carbon dioxide laser.

If the marking element is located at the bottom of the body, preferably near the center of the bottom, more preferably at the center of the bottom, it can be easily read from under the container which is always within the field of view.

Since different code types can encode different amounts of data, the requirements on data density, data processing, redundancy, etc. can be met when selecting corresponding one-dimensional or multi-dimensional data codes. Furthermore, because different types of codes mean different levels of damage to the subject and thus different effects on the container.

The 2D plane may be, for example, a plane parallel to the surface of the body. Projecting the marking element onto the 2D plane can cause it to no longer have the third dimension, e.g. the marking element no longer has a depth dimension, so that the size of the marking element can be evaluated more clearly.

According to one embodiment, alternatively or additionally, the following features may be combined, preferably: a marking element is engraved into at least one surface of the body, preferably into the inner surface, wherein the marking element is located at the bottom of the body, preferably in the center of the bottom; when projected preferably on at least one 2D plane, the marking element comprises at least one-dimensional data code, preferably usable for identification of the container; a marking element is engraved into at least one surface of the body, preferably into the outer surface, wherein the marking element is located at the bottom of the body, preferably in the center of the bottom; when preferably projected on at least one 2D plane, the marking element comprises at least one two-dimensional data code, preferably usable for identification of the container; a marking element is engraved into at least one surface of the body, preferably into the inner surface, wherein the marking element is located at the bottom of the body, preferably in the center of the bottom; the marking element, when preferably projected on at least one 2D plane, comprises at least one three-dimensional data code, preferably usable for the identification of the container; a marking element is engraved into at least one surface of the body, preferably into the outer surface, wherein the marking element is located at the bottom of the body, preferably in the center of the bottom; when projected preferably on at least one 2D plane, the marking element comprises at least one-dimensional data code, preferably usable for identification of the container; a marking element is engraved into at least one surface of the body, preferably into the outer surface, wherein the marking element is located at the bottom of the body, preferably in the center of the bottom; when preferably projected on at least one 2D plane, the marking element comprises at least one two-dimensional data code, preferably usable for identification of the container; and/or the marking element is engraved into at least one surface of the body, preferably into the outer surface, wherein the marking element is located at the bottom of the body, preferably in the center of the bottom; when preferably projected on at least one 2D plane, the marking element comprises at least one three-dimensional data code, which is preferably usable for the identification of the container.

According to a preferred embodiment, the marking element is engraved into at least one outer surface of the body.

According to an embodiment of the first, second and third aspect, alternatively or additionally, preferably, the data code comprises a plurality of dot-like elements and/or line-like elements, preferably in the form of at least one matrix code, preferably at least one dot matrix code, when preferably projected on at least one 2D plane. The dots and lines are not only easy to manufacture but also stable in readability.

The 2D plane may be, for example, a plane parallel to the surface of the body. The projection of the marking element on the 2D plane can be such that it no longer has a third dimension, for example the marking element no longer has a depth dimension, so that the elements comprised by the data code can be evaluated more clearly.

According to a preferred embodiment, the data code comprises a plurality of dot-like elements and line-like elements in the form of a matrix code.

According to an embodiment of the first, second and third aspect, alternatively or additionally, preferably, (i) the marking element is manufactured by and/or is capable of being manufactured by at least one laser ablation technique, at least one etching technique, preferably at least one dry etching technique, at least one lithography technique, at least one blasting technique and/or at least one surface modification technique, without first ablating the material with at least one laser and then performing at least one treatment with a plasma; and/or (ii) the marking element can be read by at least one camera and/or light, wherein the light is preferably light emitted by at least one laser and/or at least one light emitting diode, and the light preferably has a wavelength in the visible, infrared and/or ultraviolet spectrum.

Such as CO₂Lasers such as carbon dioxide lasers, Diode Pumped Solid State (DPSS) lasers, fiber lasers or flash lamp pumped solid state lasers are commercially available, making implementation more straightforward. In practice, particular preference is also given to UV lasers, which preferably have a wavelength of 250 to 500 nm. Such lasers are suitable for ablation techniques due to their rapidity, reliability and ability to fabricate small structures. However, lasers with wavelengths between 250 and 600nm may also be preferably used. Furthermore, dry etching techniques are also preferably used, which are particularly suitable in the field of pharmaceutical containers, since they do not generate contaminants during application.

The machine-readable marking element enables automation of operations involved with the container. For example, commercial solutions are possible in which the reading process can be carried out directly by means of a marking element which can be read by means of a camera and/or a light source.

According to one embodiment, alternatively or additionally, the following features may be combined, preferably: the marking element is produced by at least one laser ablation technique, at least one etching technique, preferably at least one dry etching technique, at least one lithography technique, at least one sandblasting technique, at least one surface modification technique, without first ablating the material with at least one laser and then at least one treatment with a plasma; the marking element can be manufactured by at least one laser ablation technique, at least one etching technique, preferably at least one dry etching technique, at least one lithography technique, at least one sandblasting technique and/or at least one surface modification technique, without first ablating the material with at least one laser and then subjecting it to at least one treatment with a plasma.

According to one embodiment, alternatively or additionally, the following features may be combined, preferably: the marking element can be read by at least one camera; the marking element may be read by light, wherein the light is preferably light emitted by at least one laser, and preferably the light has a wavelength in the visible spectrum; the marking element can be read by at least one camera; the marking element can be read by light, wherein the light is preferably light emitted by at least one laser, and preferably the light has a wavelength in the infrared spectrum; the marking element can be read by at least one camera; the marking element may be read by light, wherein the light is preferably light emitted by at least one laser, and preferably the light has a wavelength in the ultraviolet spectrum; the marking element can be read by light, wherein the light is preferably light emitted by at least one light emitting diode, and preferably the light has a wavelength in the visible spectrum; the marking element can be read by light, wherein the light is preferably light emitted by at least one light emitting diode, and preferably the light has a wavelength in the infrared spectrum; and/or the marking element can be read by light, wherein the light is preferably light emitted by at least one light emitting diode, and preferably the light has a wavelength in the ultraviolet spectrum.

According to a preferred embodiment, the marking element is manufactured by or may be manufactured by at least one laser ablation technique.

According to an embodiment of the first, second and third aspect, alternatively or additionally, preferably, the container, preferably its body: (i) comprises or consists of glass and/or at least one polymer material, preferably the glass may be a silicate glass such as an aluminosilicate glass and/or a borosilicate glass; and/or (ii) at least partially in the form of a syringe, in the form of a cartridge, in the form of a vial and/or in the form of a further medicament container, wherein preferably the bottom of the body has at least partially a concave shape, and wherein preferably the centre of the osculating circle at least one point of the bottom of the body is arranged on the side opposite to the body with respect to the bottom of the body.

If the container (preferably its body) is designed with a bottom having a concave shape, the code engraved into the bottom, preferably into the outer surface of the bottom, can be better protected against mechanical damage.

According to one embodiment, alternatively or additionally, the following features may be combined, preferably: container, preferably body: comprises or consists of a glass, preferably the glass may be a silicate glass such as an aluminosilicate glass; comprising borosilicate glass; comprising at least one polymeric material; designed at least partially in the form of a syringe barrel; designed at least partially in the form of a cartridge; designed at least partially in the form of a vial of penicillin; designed at least partially in the form of a further medicament container; designed in the form of an at least partially cartridge, wherein the bottom of the body has an at least partially concave form, wherein preferably the center of the osculating circle at least one point of the bottom of the body is arranged on the side opposite the container with respect to the bottom of the body; designed in the form of an at least partially penicillin bottle, wherein the bottom of the body has an at least partially concave form, wherein preferably the center of the osculating circle at least one point of the bottom of the body is arranged on the side opposite the container with respect to the bottom of the body; and/or in the form of an at least partially further medicament container, wherein the bottom of the body has an at least partially concave form, wherein preferably the centre of the osculating circle at least one point of the bottom of the body is arranged on the side opposite the container with respect to the bottom of the body.

According to a preferred embodiment, the container comprises or consists of glass and is designed in the form of a vial.

According to an embodiment of the first, second and third aspect, alternatively or additionally, it is preferred that the tempering operation is performed at least partially on the body at the location where the marking element is preferably provided, wherein preferably the tempering operation is performed at a temperature between 300 ℃ and 400 ℃ and/or for 10 minutes to 25 minutes.

By means of a corresponding tempering, cracks, preferably micro-cracks, can be prevented from forming or further propagating on the body. Furthermore, it has been observed that a corresponding tempering enables cleaning of the container, preferably of the main body, which feature is particularly practical in the field of pharmaceutical containers. Preferably, the tempering has a sterilizing effect, so that the container, preferably the body, becomes sterile, which is also particularly practical in the field of pharmaceutical containers.

According to one embodiment, alternatively or additionally, the following features may be combined, preferably: preferably a tempering operation is performed at least partially on the body at the location of the marking element; preferably the tempering operation is performed at least partially on the body at the location of the marking element, preferably at a temperature between 300 ℃ and 400 ℃ and for a time between 10 minutes and 25 minutes; preferably at least partially tempering the body at the location of the marking element, the tempering being performed at a temperature between 300 ℃ and 400 ℃; preferably, a tempering operation is performed at least partially on the body at the location of the marking element, which tempering operation lasts from 10 minutes to 25 minutes.

According to a fourth aspect, the present invention solves the above problem by a method of manufacturing a container for containing at least one pharmaceutical composition, comprising the steps of:

-providing at least one body, preferably the body is at least partially hollow and has at least one closed end, two open ends and/or at least one opening;

-identifying at least one position on the body where the body has at least one stress parameter, the stress parameter preferably having a value less than or equal to at least one threshold value in at least one state condition;

wherein the threshold value is derived and/or may be derived from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one surface and/or volume region of the body with or without the marking element; wherein at least one mean value is obtained or obtainable by simulation of a stress parameter of at least a portion of a surface and/or volume region of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average.

-providing at least one marking element at the identified position, which marking element can be used for identifying the container.

The present invention is based on the surprising finding that: if the position of the marking element is chosen such that one or more stress parameters at the position of the marking element are limited to a certain threshold value, the marking element may be provided on the container, preferably on its body, during the manufacture of the container, for example by a technique of weakening the material by material ablation or the like. Thus, the marking element can be permanently engraved into the container at a position that meets this criterion, while still ensuring a high strength of the container, despite damage of the marking element to the structure of the body.

With regard to the further advantages resulting from the selection of the location based on the stress parameter, reference is made to the comments provided above in connection with the first aspect of the invention, which comments apply here as well, mutatis mutandis.

According to an embodiment of the fourth aspect, alternatively or additionally, preferably, confirming the position on the body comprises the steps of:

-evaluating the simulation result of the subject and identifying at least one region in which the stress parameter has a value smaller than a threshold value, preferably an average value; and

-selecting a location to be at least partially within the identified area.

The region identified as the preferred position of the marking element may be selected such that at least one value of a stress parameter obtained by simulation of the region satisfies a threshold criterion. Thus, each point in the area satisfies the threshold criteria.

Alternatively, the preferred location may be selected such that the average of the stress parameters obtained from the simulation for that region meets the threshold criteria. In this case, individual points in the identified area may not meet the criterion, but on average the area may meet the criterion, which is a practical and more conservative approach.

According to an embodiment of the fourth aspect, alternatively or additionally, preferably, the step of providing a marker element may comprise the steps of: ablating and/or etching material of at least one surface area of the body at the identified locations, wherein the ablating and/or etching is preferably performed by at least one first laser, at least one etching technique, preferably at least one dry etching technique, at least one lithography technique, at least one sandblasting technique, at least one surface modification technique, without first ablating the material by at least one laser and then performing at least one treatment with a plasma, and/or processing at least one volume area of the body at the identified locations to generate marking elements, preferably by the first laser, which marking elements are preferably data codes, preferably read by at least one camera and/or light, wherein the light is preferably light emitted by at least one second laser and/or at least one light emitting diode, preferably the light has a wavelength in the visible, infrared and/or ultraviolet spectrum; wherein the first laser is preferably (i) a Diode Pumped Solid State (DPSS) laser, a fiber laser, an ultraviolet laser, a carbon dioxide laser or a flash lamp pumped solid state laser, (ii) a pulsed laser, preferably (a) having a pulse duration of between 100ps and 500ns, preferably 100ns, (b) having a pulse energy of between 1 and 500 μ J, (c) having a pulse repetition rate of between 10 and 400kHz, and/or (d) having an RMS power of between 1 and 100 watts, preferably 5 watts, and/or (iii) having a wavelength of between 250 and 600nm, preferably 368 nm.

In the pharmaceutical field, lasers such as carbon dioxide lasers, Diode Pumped Solid State (DPSS) lasers, fiber lasers or flash lamp pumped solid state lasers are preferably used, since it allows the fabrication of very small structures. In practice, particular preference is also given to UV lasers, which preferably have a wavelength of 250 to 500 nm. Such lasers are suitable for ablation techniques due to their rapidity, reliability and ability to fabricate small structures. However, lasers having a wavelength between 250 and 600nm may also be preferably used.

In the pharmaceutical field, dry etching techniques may also be preferred because they do not produce contamination. Both dry etching and laser are based on plasma/solid interactions.

According to an embodiment of the fourth aspect, alternatively or additionally, preferably, the step of providing a marker element may comprise the steps of: ablating and/or etching material of at least one surface area of the body at the identified locations, wherein said ablating and/or etching can preferably be performed by at least one first laser, at least one etching technique, preferably at least one dry etching technique, at least one lithography technique, at least one sandblasting technique, at least one surface modification technique, without first ablating the material by at least one laser and then performing at least one treatment with a plasma, and/or processing at least one volume area of the body at the identified locations thereby generating marking elements, preferably with the first laser, wherein the marking elements are preferably data codes, which can be read by at least one camera and/or light, wherein the light is preferably light emitted by at least one second laser and/or at least one light emitting diode, preferably the light has a wavelength in the visible, infrared and/or ultraviolet spectrum, wherein the first laser is preferably (i) a Diode Pumped Solid State (DPSS) laser, a fiber laser, an ultraviolet laser, a carbon dioxide laser or a flash lamp pumped solid state laser, (ii) a pulsed laser, preferably (a) having a pulse duration of between 100ps and 500ns, preferably 100ns, (b) having a pulse energy of between 1 and 500 μ J, (c) having a pulse repetition rate of between 10 and 400 kHz; and/or (d) has an RMS power of between 1 and 100 watts, preferably 5 watts, and/or (iii) has a wavelength of between 250 and 6500nm, preferably 368 nm.

By means of a corresponding tempering, further propagation of cracks, in particular micro-cracks, in the body can be prevented. Furthermore, it has been observed that a corresponding tempering results in a cleaning of the container, preferably of the main body, which feature is particularly practical in the field of pharmaceutical containers.

According to one embodiment, the setting of the marking element preferably comprises the steps of: ablating material of at least one surface region of the body at the identified locations.

According to one embodiment, it is particularly preferred to use an ultraviolet laser.

According to an embodiment of the fourth aspect, alternatively or additionally, preferably, the method further comprises the step of: preferably, a tempering operation is performed at least partially on the body at the location of the marking element, preferably at a temperature between 300 ℃ and 400 ℃ and/or for a time between 10 minutes and 25 minutes.

It is clearly understood by the skilled person that the structural features disclosed according to any of the first, second and third aspects of the invention may also be subject to the features of the fourth aspect of the invention.

Other related aspects of the invention are discussed below.

As mentioned above, glass containers such as vials used in the pharmaceutical industry are also typically subjected to loads such as axial and lateral compression during handling, processing and transportation. Both types of compression produce compressive and/or tensile stresses. Preferably, these stresses occur at the outer and/or inner surface of the container (preferably the body).

According to one embodiment, the container, preferably the body, is a vial of penicillin.

According to an embodiment, alternatively or additionally, the size of the vial may be 2R, 4R, 6R, 8R, 10R, 15R, 20R, 25R, 30R, 50R or 100R.

According to an embodiment, alternatively or additionally, both types of loads may be present in different surface and/or volume regions of the container, preferably of the body. For example, lateral compression is present in the region of the neck and/or axial compression is present in the region of the base.

It is particularly noted that the compressive strength in both the axial and lateral directions can be verified by appropriate strength experiments. For example, the axial compression strength of a vial of penicillin may be based on DIN EN ISO 8113: 2004, by applying an axial compressive load at a constant load rate until the sample fails. The lateral compressive strength of the vial can be determined by applying a constant rate radial (straight radial/lateral) compressive load until the sample fails.

With respect to axial compression, the inventors have specifically identified the following: for example, during packaging of the container, the container may be subjected to pressure from above, thereby compressing axially. This is the case, for example, when containers are stacked on top of each other. In addition, during freeze-drying (lyophilization), there is also often axial compression. This is because in one application of freeze drying a holder is attached to a container, such as a vial, preferably a glass vial, to hold the container, which causes mechanical stress in the form of axial compression to be applied to the container. In another application of freeze-drying, the container may alternatively or additionally be placed on a cooling plate and pressed from above, which causes mechanical stress in the form of axial compression to be applied to the container. Likewise, when the container is preferably closed using a jaw closure, there will also be axial compression.

Of course, tensile stresses may be present whether in axial or lateral compression. Also, compressive stresses will exist in both axial and lateral compression.

Axial compression is known to occur under axial loads. It is well known that lateral compression occurs under lateral loads.

With respect to lateral compression, the inventors have specifically identified the following: for example, during processing of the container, there may be lateral compression within the container.

As a tendency, it can be said that a position where the tensile stress is low may be preferable for setting the marking element, and/or a position where the absolute value of the compressive stress is high may be preferable for setting the marking element. Note that the value of tensile stress is a positive value, while the value of compressive stress is a negative value. Thus, a high absolute value of the compressive stress means a higher compressive stress.

In particular, the inventors have also found that according to one embodiment, locations having a tensile stress of up to 150MPa may still be considered as preferred locations for providing the marking element.

Within the context of the present invention, every pharmaceutical composition deemed suitable by the skilled person is contemplated. Pharmaceutical compositions are compositions that include at least one active ingredient. Preferably, the active ingredient may be a vaccine, antibody or other biological agent. The pharmaceutical composition may be a fluid, a solid, or a combination thereof, with a fluid composition being preferred. Preferred solid compositions may be granules such as powders, tablets or capsules. Further preferred pharmaceutical compositions may be non-oral, i.e. meaning compositions that are administered by a route other than oral. Non-oral administration may be carried out by injection or by insertion of an indwelling catheter, or injection may be carried out, for example, using a needle (typically a hypodermic needle) and syringe.

Other relevant aspects related to the container will be discussed below. For the sake of discussion, it is assumed here that the container, preferably its body, is preferably made of glass. It is furthermore assumed that the container is preferably designed in the form of a vial. Of course, however, all other types of containers are possible.

The above-mentioned pharmaceutical glass containers should have a sufficiently high strength, especially if they are to be placed in an automatic capping machine which applies a large axial load to the vial. Higher axial loads can be observed during the use of glass vials in automatic sampling machines in scientific laboratories or in medical institutions, or during capping, transport and storage of glass vials. In addition to being somewhat resistant to axial loading, the glass container should also have a sufficiently high burst strength. For example, a burst pressure test may be suitable for evaluating the strength of a container during lyophilization to find the weakest point on the inner or outer surface of the container. The burst strength of the glass container of the drug is important if lyophilization is required after filling the drug formulation into the glass container.

Since the use of glass containers in the pharmaceutical industry allows only a very low rate of damage when mechanical stresses or pressure changes are applied, glass containers for holding pharmaceutical preparations should have a sufficiently high strength, in particular a capacity to withstand high axial loads and a sufficiently high breaking strength.

In addition, it should have the ability to withstand certain pressures during the lateral compression test described below.

In the pharmaceutical industry, containers are primary packages of pharmaceutical products. Glass containers are the most commonly used of traditional materials because they ensure stability, visibility, durability, rigidity, moisture resistance, are easy to close and are economical. The pharmaceutical glass containers currently on the market include glass containers made of glass tubes and blow-molded glass containers.

Glass vials for pharmaceutical packaging must pass many mechanical tests. For example, in the case of the use of a vial in an automatic sampling machine in a scientific laboratory or in a medical institution, or in the case of capping, transporting and storing vials, it is necessary to determine the high axial load of the vial by means of a so-called "vertical compression test" (also referred to as "axial compression test"). In addition to being somewhat resistant to axial loading, the glass container should also have a sufficiently high burst strength, which can be determined by the so-called "burst pressure test". For example, if lyophilization is desired after filling a pharmaceutical formulation into a glass container, the burst pressure test is suitable for finding the weakest point on the inner or outer surface of the container.

Another common mechanical test commonly used to determine the mechanical strength of glass vials is the so-called "lateral compression test". For example, the effect that a particular back pressure may have on a vial during transport in a depyrogenation tunnel or on a filling line can be determined by this test. In this test, a glass vial may be placed between the upper and lower portions of the test tool, as shown in fig. 4a (described in more detail below), and then a predetermined load is applied directly to the main body region of the glass vial.

The glass container according to the invention or the glass containers comprised in the plurality of glass containers according to the invention may have any size or form that a person skilled in the art considers suitable in the context of the invention. Preferably, the top region of the glass container comprises an opening through which the pharmaceutical composition can be placed into the internal volume of the glass container. The glass container comprises the following container parts: a glass tube having a first end and another end; and a glass bottom closing the glass tube at the other end. Preferably, the glass container is of one-piece design, which is prepared by providing a glass tube and closing one end of the glass tube (i.e. the end will become the opening of the glass container), whereby the top area, the joining area, the neck area and the shoulder area are obtained, and then shaping the other end of the glass tube so as to obtain a closed glass bottom. Preferably the glass container is a pharmaceutical glass container, more preferably one selected from a vial, ampoule or combination thereof, wherein it is particularly preferably a vial of penicillin.

The glass of the container may be any type of glass, which may be composed of any material or combination of materials that the skilled person would consider suitable in the context of the present invention. Preferably, the glass is suitable for packaging pharmaceuticals. The glass is particularly preferably form I, more preferably form I b, according to the definition of glass type in section 3.2.1 of the european pharmacopoeia (7 th edition 2011). Additionally or alternatively, the glass may be selected from the group consisting of borosilicate glass, aluminosilicate glass, soda lime glass, and fused silica, or may be a combination of at least two thereof. According to the instructions in this document, Al in the aluminosilicate glass is present in each case based on the total weight of the glass₂O₃Is more than 8% by weight, preferably more than 9% by weight, particularly preferably in an amount of between 9% and 20% by weight. Preferred aluminum is based in each case on the total weight of the glassSilicate glass B₂O₃Less than 8% by weight, preferably up to 7% by weight, particularly preferably in the range from 0% to 7% by weight. According to the instructions in this document, B in borosilicate glasses is based in each case on the total weight of the glass₂O₃Is at least 1 wt.%, preferably at least 2 wt.%, more preferably at least 3 wt.%, more preferably at least 4 wt.%, even more preferably at least 5 wt.%, and particularly preferably in the range of 5 to 15 wt.%. Preferred borosilicate glasses are those in which Al is present, based in each case on the total weight of the glass₂O₃Is less than 7.5 wt.%, more preferably less than 6.5 wt.%, particularly preferably in the range of 0 to 5.5 wt.%. On the other hand, Al in borosilicate glasses is present in each case based on the total weight of the glass₂O₃Is in the range of 3 to 7.5 wt.%, preferably in the range of 4 to 6 wt.%.

Further preferably, the glass according to the invention is substantially free of boron (B). Wherein "substantially free of B" refers to glass that is free of B that is intentionally added to the glass composition. This means that B can still be present as an impurity, the content of B preferably not exceeding 0.1 wt.%, more preferably not exceeding 0.05 wt.%, in each case based on the total weight of the glass.

Axial load and burst pressure

The mechanical resistance of the penicillin bottles to axial compression can be achieved by a mechanical resistance according to DIN EN ISO 8113: a vertical load strength test conducted 2004 ("glass container-vertical load resistance-test method") to determine where a compressive force can be applied in the axial direction and increasing the pressure at a constant load rate of 500N/min until the container fails.

The mechanical resistance of the penicillin bottles to internal pressure can be determined by the method according to DIN EN ISO 7458: the burst strength test conducted in 2004 ("glass container-internal pressure resistance-test method") determined that hydraulic pressure could be applied from inside the vial therein and increased at a constant load rate of 5.8bar/s until the container broke.

Lateral compression test

The mechanical resistance of the main body part of the vial to diametral compression can be improved by modifying it from DIN EN ISO 8113: 2004 ("glass container-vertical load resistance-test method") in which compressive forces in the diametral (radial) direction can be applied at two opposite locations of the exterior surface geometry of the vial body. The compressive force was increased using a universal testing machine at a constant load rate of 1500N/min until the container was broken (breakage was again detected as a sharp drop in the force-time diagram f (t)). The diametral load is applied by two opposite uniaxial concave steel surfaces between which the main part of the vial is placed parallel to the axis. One of the concave surfaces is configured to be self-adjusting to enable compensation for geometric irregularities. The concave radius of the two steel surfaces is 25% greater than the radius of the outer diameter of the main body portion so that the load is applied along two opposite lines. The width of the concave steel surface is selected to be greater than the height of the main body part of the penicillin bottle.

Neck squeeze test

The mechanical resistance of the penicillin bottle neck against diameter compression can be improved by changing from DIN EN ISO 8113: 2004 ("glass container-vertical load resistance-test method"), wherein diametral (radial) compressive forces may be applied at two opposite locations of the exterior surface geometry of the vial neck. The compressive force was increased using a universal testing machine at a constant load rate of 2000 n/min until the container was broken (breakage was detected as a sharp drop in the force-time diagram f (t)). The diametral load is applied by two opposite uniaxial concave steel surfaces between which the neck of the vial is placed parallel to the axis. One of the concave surfaces is configured to be self-adjusting to enable compensation for geometric irregularities. The concave radius of the two steel surfaces is 25% greater than the radius of the outer diameter of the neck, so that the load is applied along two opposite lines. The width of the concave steel surface is selected to be slightly smaller than the height of the neck of the penicillin bottle.

Drawings

Various aspects of the invention may become apparent to those skilled in the art from the following detailed description of the preferred embodiment when taken in conjunction with the accompanying drawings.

Figure 1 shows a container with a marking element at the bottom according to the first, second and third aspect of the invention;

2a-2c schematically show different marking elements engraved into glass;

FIG. 3a shows a schematic representation of an apparatus for axial compression testing;

FIG. 3b exemplarily shows a contour plot of stress distribution on the outer surface of the sample in an axial compression test;

FIG. 4a shows a schematic representation of an apparatus for lateral compression testing;

FIG. 4b exemplarily shows a contour plot of stress distribution on the outer surface of the sample in a lateral compression test;

fig. 5 shows a perspective cross-sectional view of a vial model with different parts;

FIG. 6a shows a contour plot of the stress distribution of the vial of FIG. 5 under axial compression;

FIG. 6b shows a contour plot of the stress distribution of the cylindrical wall of the vial of FIG. 5 under axial compression;

FIG. 6c shows a contour plot of the stress distribution under axial compression of the heel of the vial of FIG. 5;

FIG. 6d shows a contour plot of the stress distribution at the bottom of the vial of FIG. 5 under axial compression;

FIG. 7a shows a contour plot of the stress distribution of the vial of FIG. 5 under lateral compression;

FIG. 7b shows a contour plot of the stress distribution under lateral compression of the cylindrical wall portion of the vial of FIG. 5;

FIG. 7c shows a contour plot of the stress distribution under lateral compression of the heel of the vial of FIG. 5;

FIG. 7d shows a contour plot of the stress distribution under lateral compression of the bottom of the vial shown in FIG. 5; and

fig. 8 is a flow chart of a method according to the fourth aspect of the invention.

Detailed Description

Fig. 1 shows a container in the form of a vial with a marking element at the bottom of the vial.

Fig. 2a shows a close-up view of the marking element. For demonstration purposes, the marking elements herein are engraved into the glass substrate.

Fig. 2b shows another marking element engraved into the bottom outer surface of the vial. The dimensions of the marking elements can be deduced from the description in the figures. The marking element has a dimension in the first direction of 1.18 mm. Since the marker element is square, its dimension in the second direction is also 1.18 mm.

Fig. 2c shows another marking element engraved into the bottom outer surface of the vial. The dimensions of the marking elements can be deduced from the description in the figures. The marking element has a dimension in the first direction of 1.22 mm. Since the marker element is square, its dimension in the second direction is also 1.22 mm.

Figure 3a shows a schematic representation of the apparatus for axial compression testing. The device can be used to check the axial compression strength. The axial compressive strength of, for example, a glass vial 1a may be based on DIN EN ISO 8113: 2004 was determined by applying an axial compression load F at a constant load rate until the specimen (vial 1a) broke. Here, the vial 1a is clamped between a self-adjustable steel plate 3a and a rigid steel plate 5 a.

Fig. 3b shows an exemplary contour plot of the stress distribution on the outer surface of a 2mL tubular glass vial under axial compression, which can be obtained by the axial compression test shown in fig. 3 a.

Figure 4a shows a schematic representation of the apparatus for lateral compression testing. The device can be used to check the lateral compressive strength. The lateral compressive strength of, for example, a glass vial 1b may be based on a tensile strength modified from DIN EN ISO 8113: 2004 (see section above for lateral compression test) was determined by applying a lateral compression load F of constant load rate until the sample (vial 1b) failed. Here, the vial 1b is clamped between a self-adjustable steel plate 3b and a rigid steel plate 5 b.

Fig. 4b exemplarily shows a contour plot of the stress distribution on the outer surface of a 2mL tubular glass vial under lateral compression, which can be obtained by the lateral compression test shown in fig. 4 a.

From fig. 3b and 4b it can be concluded that the two loads described above result in a relatively low tensile stress in the centre of the outer surface of the base of the vial (or that they result in a uniform compressive stress). This indicates the preferred location for laser marking here.

In this regard, it is noted that the strength of glass can be considered as a presumption of its surface quality, and thus, the strength of glass varies with changes in surface conditions during handling, processing, and transportation. But typically the (tensile) strength values of the glass products are between about 30 and 70 MPa. Therefore, the lower limit of the reasonable specification of the strength at which laser marking can be performed is a tensile stress value of 70 MPa. According to the geometrical structure and the loading condition of the penicillin bottle, the magnitude of the compressive force required for generating the tensile stress of 70MPa on the outer surface of the base of the penicillin bottle is different.

It is evident from the figure that different critical areas exist at different loads. However, the concept of the invention allows the position to be ascertained by means of simulation results, so that only low tensile stresses (or uniform compressive stresses) are present, and consequently marking elements can be provided at the corresponding positions without the risk of reducing the stability of the vial. This is practical because locations with tensile stress have to be avoided, whereas it is beneficial to provide the marking element at locations with compressive stress.

In any case, based on the simulation results, it is also possible to determine an average value of the stress parameter, which in turn can be used as a relative value for setting the threshold value according to the invention (in fact, this average value can be used as a basis for calculating a sum, which in turn is related to the threshold value). This also illustrates that various simulation data can be used to determine the threshold value based on the load that may be applied to the container (e.g. a vial of penicillin, preferably the vial of penicillin as shown in fig. 3a and 4 a) during use. This constitutes a rather flexible approach.

In other words, if the results such as those shown in fig. 3b and 4b are obtained by simulating the vial that needs to be marked, then the preferred position can be defined at the bottom of the vial based on the mean values obtained from the profiles. For example, a region of the vial bottom that has a tensile stress below a first threshold in a first condition (e.g., axial compression) and a tensile stress below the first threshold in a second condition (e.g., lateral compression) may be preferred locations. And/or, for example, a region of the vial bottom where the first principal stress is less than a certain threshold under certain condition conditions (e.g., axial or lateral compression) may be a preferred location.

Fig. 5 shows a perspective sectional view of a model of a vial 7. In one embodiment, the marker element must be provided on a preselected portion of the container (preferably in the form of a vial 7) due to regulations regarding readability of the marker element, etc. The preselected portion may be, for example, the cylindrical wall portion 9 of the vial, the heel portion 11 of the vial, or the bottom portion 13 of the vial. It is advantageous to limit the simulation to a corresponding portion of the container so that only the value of that portion needs to be considered when determining the average value and thus the threshold value.

Fig. 6a to 6d and 7a to 7d show different contour diagrams of the first principal stress distribution under axial and lateral compression, respectively, as will be described in detail below. The key code for fig. 6a-6d and 7a-7d is selected so that only the tensile stress is shown from light to dark. The area corresponding to the compressive stress (value less than zero) is brighter. Whereas the first principal stress is shown in the contour plot, this means that the maximum stress of each point is shown regardless of the stress direction. Although each contour map shows only one quarter of the entire element, this is sufficient because the element is rotationally symmetrical.

For axial compression:

fig. 6a shows a contour diagram of the entire vial 7 as shown in fig. 5. From this distribution, the average weighted value of the first principal stress can be calculated to be 15.7 MPa.

Fig. 6b shows a contour diagram of the cylindrical wall 9 of the vial 7 only as shown in fig. 5. From the distribution of the contour map, the average weighted value of the first principal stress was calculated to be 17.6 MPa.

Fig. 6c shows a contour diagram of only the heel 11 of the vial 7 as shown in fig. 5. From this distribution, the average weighted value of the first principal stress can be calculated to be 22.2 MPa.

Fig. 6d shows a contour diagram of the bottom 13 of the vial 7 only as shown in fig. 5. From this distribution, the average weighted value of the first principal stress can be calculated to be-4.3 MPa.

For lateral compression:

fig. 7a shows a contour diagram of the entire vial 7 shown in fig. 5. From this distribution, the average weighted value of the first principal stress can be calculated to be 28.0 MPa.

Fig. 7b shows a contour diagram of the cylindrical wall 9 of the vial 7 only as shown in fig. 5. From this distribution, the average weighted value of the first principal stress can be calculated to be 26.9 MPa.

Fig. 7c shows a contour diagram of only the heel 11 of the vial 7 as shown in fig. 5. From this distribution, an average weighted value of the first principal stress of 19.8MPa can be calculated.

Fig. 7d shows a contour diagram of the bottom 13 of the vial 7 of fig. 5. From this distribution, an average weighted value of the first principal stress of 43.4MPa can be calculated.

From an evaluation of fig. 6a-6d and 7a-7d it has been found that different stress values and thus different average weighting values can be obtained from the simulations shown in the contour diagrams of fig. 6a-6d and 7a-7d, depending on the part of the vial 7 where the marker element should be placed. Furthermore, the results of axial and lateral compression, and thus the average, are different. This in turn means that different threshold values are obtained depending on the part of the marker element that is arranged on the vial 7. Or in other words, the regions identified as "preferably" capable of being provided with marking elements may have different stress values, thus different average values, and thus different threshold values, for different parts of vial 7. Thus, while a certain threshold may be used to determine a preferred location on the bottom under lateral compression, it may not be suitable for determining a preferred location on another portion under lateral compression.

In practice, this clearly shows that, since the threshold value is defined with respect to the mean value, the inventive concept can be applied without having to take into account the geometry, size and shape of the respective container.

For example, assuming that it is necessary to provide a marking element on the bottom 13 of the vial 7 (e.g. not available for writing and/or reading the marking element due to the non-readability of other parts of the vial), the relevant corresponding force parameter can be taken as the first principal stress and the state condition as the lateral compressive force 1700N, and finally the threshold value is set as the sum of the average weighted average (i.e. the average weighted average obtained by simulation) and 100% of the absolute value of this average weighted average. Therefore, in order to determine the position at which the marking element can be arranged, a simulation of the bottom 13 of the vial 7 is carried out for the first principal stress, in which a lateral pressure of 1700N is applied.

Then, a contour map as shown in fig. 7d is generated by simulation. From this, it can be derived that the average weighted value of the first principal stress is 43.4MPa (see above for details). Finally, the threshold can be defined as 43.4MPa plus 100% of 43.4MPa, resulting in 86.8 MPa. As can be seen from the contour diagram shown in fig. 7d, the right half of the bottom 13 (area 15 in fig. 7 d) is lighter and therefore can be a suitable place for placing a marker element. In contrast, the upper left corner of the bottom part 13 shown in fig. 7d (area 17 in fig. 7 d) is darker and its value exceeds 170MPa, so the threshold criterion cannot be met and no marking element should be placed at this position.

Of course, the above is merely an example for illustrating a suitable application of the method of the present invention.

Fig. 8 is a flow chart of a method 100 according to the fourth aspect of the invention.

In step 101, at least one body is provided, which is at least partially hollow and has at least one closed end and is provided with at least one opening. For example, the body may be a vial of penicillin as shown in the model of fig. 5.

In step 103, identifying at least one location on the body where the body has at least one stress parameter, preferably a value of the stress parameter less than or equal to at least one threshold value under at least one condition; wherein the threshold value is derived and/or can be derived from at least one simulation result of at least one simulation based on a finite element method of stress parameters of at least one surface region of the body with or without the marking element; wherein at least one mean value is obtained or obtainable by simulation of a stress parameter of at least a portion of a surface region of the body; wherein the threshold is the sum of the average and less than 1000% of the absolute value of the average. For example, the stress parameter may be a first principal stress.

For example, the state condition may be a lateral compression of 1700N. For example, the first surface of the body may be a surface of the bottom of the body. For example, the threshold may be 86.8 pa as derived based on fig. 7d, described above.

In step 103a, which is comprised by step 103, the simulation results of the subject are evaluated and at least one region where the mean value of the stress parameter is less than a threshold is identified.

For example, this area may be the right half 15 of the bottom of the vial body, see fig. 7 d.

In step 103b, which step 103 comprises, the location is selected such that the location is at least partially within the identified area.

In step 105, at least one marking element is provided, which can be used to identify the container at the identified position.

In step 105a, which step 105 comprises, at the identified locations, material of at least one surface area of the body is ablated by at least one first laser. This step may be performed by, for example, an ultraviolet laser.

In step 107, a tempering operation is performed at least partially on the body.

Of course, even though the preferred embodiment discussed above with reference to the drawings refers to a product such as a vial or syringe, it will be clear to those skilled in the art that the aspects discussed are correspondingly applicable to containers of other shapes, geometries and sizes.

The principles and modes of operation of the present invention have been explained and illustrated with reference to the preferred embodiments thereof. It must be understood, however, that this invention may be practiced otherwise than as specifically explained and illustrated without departing from its spirit or scope.

List of reference numerals

1a, 1b penicillin bottle

3a, 3b steel plate

5a, 5b steel plate

7 XiLin bottle

9 wall part

11 heel part

13 bottom part

15 area

Region 17

100 flow chart

101-107 step

F load (force)