Method for determining airtightness and CCI of container having crimped sealing closure

Abstract

A method for determining the airtightness and CCI of a container having a crimped sealing closure, the method comprising: providing a container having a closed crimped sealing closure, the crimped sealing closure having an elastomeric portion; measuring a determined length between the top of the elastomeric portion and the position of the container; comparing the length with a predetermined range; and rejecting the closed containers with lengths outside the predetermined range.

Description

Technical Field

[0001] The present invention relates to a method for determining the hermeticity and container closure integrity (CCI) of a container having a crimp seal closure. Background Art

[0002] Crimp seal closures are known in the art and are used to seal containers, such as glass containers like vials. Testing the integrity or airtightness of a closed container is very important to ensure the suitability of the closure for its intended use. Methods for testing the airtightness of a crimp seal closure are known in the art, for example see European Patent 0892918B1. These methods work by applying pressure to the top of the crimp seal closure and measuring the movement of the crimp seal closure in reaction to the applied pressure. The disadvantage of these methods is that they are time-consuming, unreliable and destructive. Summary of the invention

[0003] It is an object of the present invention to provide a method of testing the integrity of a crimp seal closure which is easy, quick and non-destructive to perform while providing reliable results.

[0004] By providing a method according to claim 1, the present invention provides a rapid, reliable and non-destructive method of testing the integrity of a crimp seal closure. BRIEF DESCRIPTION OF THE DRAWINGS

[0005] Further aspects of the invention will be described with reference to the accompanying drawings, in which:

[0006] Figures 1A to 1C A crimp closure is shown, wherein

[0007] Figure 1A The crimp closure with the closure element is shown along Figure 1B The cross-section surface of the AA line shown in FIG.

[0008] Figure 1B A top view of the crimp ring is shown;

[0009] Figure 1C An isometric view of a crimp ring is shown;

[0010] Figure 2 showing a cross-sectional view of a closed crimp closure at the top of a container;

[0011] Figure 3 A closed container is shown;

[0012] Figure 4 a measurement graph showing the determined length relative to air tightness; and

[0013] Figure 5Another embodiment of a crimped closed container is shown. DETAILED DESCRIPTION

[0014] like Figures 1A to 1C The crimp seal closure shown in FIG. 1 generally comprises a crimp ring 10 ( Figure 1C ), the crimping ring 10 consists of a cylindrical body 11 having a closed end 14, the closed end 14 having a flange 12, and the flange 12 is provided with a concentric opening 13. The flange 12 has a top surface 100. The diameter of the reference circle d fits concentrically between the opening 13 and the outer wall of the cylindrical body 11. The reference circle d can be used for further measurements as described below. The material is typically aluminum or another suitable deformable material. In addition, the crimping sealing closure is provided with an elastomeric portion formed as a closure element 20, which is disc-shaped and fits into the cylindrical body 11. The closure element 20 is made of an elastic material, such as rubber. The closure element can be made of a single component, such as a rubber disc, or of multiple components, such as two rubber discs 231 and 241 (similar to Figure 1A The closure element is made of a flexible material such as rubber, polyisoprene or bromobutyl rubber.

[0015] The container 30 to be closed ( Figure 2 , in this example provided with liquid contents 60) has a cylindrical opening 31, which is provided with a circumferential flange 32. To close the container 30, a closing element 201 is placed together with the crimping ring 10 and is placed on the top of the container 30. The lower part 15 of the cylindrical crimping ring 10 extends beyond the flange 32. To close, the crimping ring 10 is pressed onto the container, thereby compressing the closing element 201 located between the crimping ring 10 and the flange 32 of the container 30. Subsequently, the lower part 15 is crimped (i.e., deformed) on the flange 32. The result is that the crimping ring 10 is connected to the container 30 in a closed form, wherein the closing element 201 is maintained under pressure, thereby closing and sealing the container 30. The pressure with which the crimping sealing closure is affixed to the container is determined by the pressure used during the crimping process. The closing element 201 has a central protrusion 21 or ridge 21. Tools for crimping a crimping closure onto a container are well known in the art. According to the invention, the central projection 21 is extended axially outwards to a certain extent by the closed crimping ring.

[0016] For many applications, especially in the pharmaceutical field, the reliability of the closure is crucial. Tests for determining the reliability of the closure are known in the art and essentially determine the pressure that the closure can withstand before a leak occurs. For example, many leak tests evaluate whether the container closure system is sufficient to maintain a sterile barrier to prevent potential contaminants. In essence, these methods apply pressure to the container to be tested (the container is closed with a crimp seal closure to be tested) and apply different pressures to the container until the seal is broken. An example of such a test is ISO21881:2019, Annex F. For specific purposes, a minimum pressure that can be prevented is required. A closed container that meets this requirement is also referred to as a gas-tight container, which means that the container has no leaks. A container with a closed closure (i.e., preventing the container from leaking, for example, according to the aforementioned ISO standard) is also likely to have container closure integrity (CCI), i.e., preventing fluid from entering the container.

[0017] According to the present invention, the closure integrity of the crimp seal closure is determined by the height of the crimp seal closure relative to the closed container. The height of the installed crimp seal closure is determined by the topmost portion of the closure element 201, i.e., the center protrusion 21. The topmost portion of the center protrusion 21 is the first measurement point. The second measurement point is located at the top surface ( Figure 1A The height X of the installed crimp seal closure can be measured between a point on circle d and the central protrusion 21, i.e. between the first measuring point and the second measuring point. The advantage is that the measurement is easy to perform and gives an accurate measurement result, since it is independent of the form of the body of the container.

[0018] In an alternative embodiment, the second measurement point is a predetermined portion of the container 30. In one embodiment, the predetermined portion is the bottom 40 of the container. This has the advantage of being easily determined, for example by placing on a measuring surface for measurement. The second measurement point can be any part of the container, for example a certain position on the shoulder of the container, or a specific point on the container indicated by a marking such as printing or etching. In this alternative embodiment, dimensional variations of the container geometry, for example due to production tolerances, are preferably taken into account to improve the measurement accuracy.

[0019] The length between the first measuring point and the second measuring point is referred to as the determined length X for the first embodiment and as L for the alternative embodiment. Figure 2An example of a closed container 30 according to the invention is shown and a determined length of the top of the closing element relative to the container is shown, in this embodiment the determined length L being measured between the top of the closing element 21 and the bottom 40 of the container. The determined length determined by the concentric circles d0 and the top of the closing element 21 is denoted as X. Figure 3 In FIG. 1 , a closed container 301 is shown having a closure 101 and a protruding closure element 201, the closure element 201 having a central protrusion 211, and two examples for measuring a certain length, wherein the certain length L1 is measured between the top of the closure element 211 and the bottom 401 of the container 301, and the certain length L2 is measured between the top of the closure element 211 and the shoulder 35 of the container 301. In addition, in Figure 3 , a certain length defined by the concentric circle d1 and the top of the closing element 211 is shown as X1.

[0020] exist Figure 5 , another embodiment of a closed container 302 of the present invention having a bottom 402 is shown. A crimping ring 102 is crimped onto a single closure element 202 with a topmost portion 212. The closure element 202 has a center portion 212 that protrudes above the crimping ring 102 after closure. A length L3 is determined from the topmost portion 212 to the bottom 402 of the container 302. In addition, in Figure 5 , a certain length defined by the concentric circle d2 and the top of the closing element 202 is represented as X2.

[0021] According to the invention, it has been found that the determined lengths (L, L1, L3, X, X1, X2) predict the airtightness performance of a closed container. In order to determine the value of the determined lengths that are relevant to the airtightness of a closed container, a calibration is required. A group of containers is closed at several values ​​of crimping force, resulting in a variation of the determined lengths of the closed container for the group of containers. The group of containers is subjected to an airtightness test, wherein for each closure cylinder the maximum pressure that still ensures the integrity of the closure is determined. When the data is presented in a graphical form, a graph such as Figure 4 The diagram shown in . On the x-axis, the determined length of the closed container is shown, wherein on the y-axis, the maximum pressure at which the container remains airtight for at least 5 seconds is shown. According to ISO 21881:2019, Annex F, the LSL line determines the required airtightness for this particular combination of crimped closure and container. The M1 line shows the line at which the minimum determined length lies, which corresponds to the determined length required at least to ensure the required airtightness. Containers that are not airtight for more than 60 seconds at the required pressure are represented by points below the LSL line, according to the requirements of ISO 21881:2019.

[0022] The topmost part of the center protrusion 21, 211, 212 as the first measurement point can be measured using an optical measuring device, for example, using a camera-based visual system or a laser-based system. Such optical measuring systems are known in the art. Generally, measurement systems for determining geometric measurements of drug containers are well known in the art. Optical systems have the advantage of not needing physical contact with the center protrusion 2, 211, 212 to be measured, thereby improving measurement accuracy. Other measuring systems can also be used, such as using a mechanical measuring tool that contacts the center protrusion 21, 211, 212. The contact force used for testing the center protrusion should be kept low to avoid affecting the measurement. A contact force between 0.01N and 0.1N is advantageous.

[0023] Devices and machines for closing containers using crimp closures are known in the art. The crimping force may vary for a particular combination of crimp closure type and container type. The crimping force is a factor in determining the sealing strength of the closure and plays a large role in determining whether a closed container will maintain the desired airtightness. Due to the unavoidable tolerances of the production machinery, the effective crimping force will vary for each closed container.

[0024] A set of calibration containers is generated by performing a calibration operation, that is, closing a set of containers with crimping parts with a nominal crimping force. The determined length of each of these containers will change with the actual crimping force. The length (ridge height) of the containers in the calibration set is measured and tested for airtightness. The airtightness test is a pass / fail test, which will produce a set of passed containers. Each of these containers has a specific length, which is distributed along a certain distribution. The highest length and the lowest length will determine the range of lengths that ensure airtightness. This will provide a reference range for determining the length, which corresponds to the test characterization of the airtightness of the closure and container combination.

[0025] In ISO 21881:2019, Appendix F, an example of an airtightness test is described, and although this test is suitable for implementing the present invention, other airtightness tests may also be used for the present invention.

[0026] Reference ranges need to be determined for each specific type of closure and container combination.

[0027] In another embodiment of the present invention, the same calibration test operation is used to determine the reference range for determining the height. The lower limit of the reference range is determined as in the previous example. The upper limit of the reference range is determined by a geometric limit, such as the maximum height of a closed container. This is determined by Figure 4The M2 line in FIG. 1 is shown. However, the airtightness and the CCI can be ensured by a higher height. The maximum height can be limited, for example, by the maximum size for further use of the closed container, for example to ensure compatibility with use in pharmaceutical applications or use in devices with a maximum accepted size for the closed container.

[0028] In production, each crimped container is measured and compared to a reference range, preferably immediately after filling and closing. The container can be filled with a liquid, such as a liquid containing a pharmaceutical ingredient. Containers within the reference range must meet the required airtightness and CCI and are further processed. Containers outside the reference range have uncertain airtightness and CCI and are therefore rejected or sorted. Production lines and methods are known in the art, for example as described in US9796489.

[0029] By means of a simple measurement of the determined length, the airtightness and the CCI of the closed container can be determined quickly and reliably. It is particularly advantageous to carry out the measurement downstream of the closing machine.

[0030] The container may be any type of container having an opening suitable for crimping a sealed closure, such as a syringe, a vial or an ampoule. The container may be made of glass, a polymer or any other suitable material.

Claims

1. A method for determining the airtightness of a container having a crimp seal closure, the method comprising the steps of: Providing a container having a closed crimp seal closure, the crimp seal closure comprising an elastomeric portion; measuring a determined length between a top of the elastomeric portion and a location on the container; comparing the length to a predetermined range; and Closed containers whose lengths are outside the predetermined range are rejected.

2. The method according to claim 1, wherein: The length measurement is determined between the top of the elastomeric portion and a location on the crimp seal closure on a reference diameter (d), Preferably, wherein the location on the reference diameter (d) on the crimp sealing closure is located on the top surface of the crimp sealing closure.

3. The method according to claim 1, wherein: The length measurement is determined between the top of the elastomeric portion and the bottom of the closed container.

4. A method according to any one of the preceding claims, wherein: The elastomeric portion comprises two stacked rubber components, wherein a topmost portion protrudes above a crimping ring in a closed state, wherein the determined length is measured between a topmost portion of the top rubber component and a position on the container.

5. A method according to any one of the preceding claims, wherein: The predetermined range is determined by calibration testing.

6. A method according to any one of the preceding claims, wherein: One of the limits of the predetermined range is determined by a maximum length.

7. A method according to any one of the preceding claims, wherein: The container is a vial.

8. A method according to any one of the preceding claims, wherein: The step of providing a container with a closed crimp seal closure comprises the steps of providing a container with an open top; providing a crimp seal having a crimp ring and a rubber closure element; and crimping the crimp seal onto the open top by deforming the crimp ring, thereby closing the container.

9. The method of claim 8, further comprising filling the container with a liquid prior to closing the container.

10. The method according to claim 9, wherein: The liquid includes a pharmaceutical composition.

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