CONTAINERS HAVING CLOSED ENDS, CONTAINER ASSEMBLIES AND MEDICAL DEVICES HAVING SUCH CONTAINERS

Abstract

Container assemblies for accommodating pharmaceutical compositions are provided. The container assembly includes a container and a plunger. The container has a hollow cylindrical body with an open end and a closed end, which is closed by a bottom portion. The hollow cylindrical body has a length (L), an outer diameter (DO), and an inner diameter with a length to outer diameter ratio between 3:1 and 15:1. The hollow cylindrical body and the bottom portion are formed integrally and of the same material, which is a glass or polymer material. The container has an inner surface with an average Zn-leachability of 0.00085 g/cm.sup.2 or less. The plunger is inside the hollow cylindrical body at the open end, is pierceable by a cannula, and is slidable relative to the hollow cylindrical body from the open end towards the closed end.

Claims

1. A container for accommodating pharmaceutical compositions, comprising: a hollow cylindrical body with an open end and a closed end opposite to the open end, the open end and the hollow cylindrical body being configured to receive a plunger that is slidable relative to the hollow cylindrical body from the open end to the closed end, the closed end being closed by a bottom portion, the hollow cylindrical body and the bottom portion being formed integrally and of a common material, which is a glass or polymer material, the hollow cylindrical body having an inner surface, a length (L) between 35 mm and 120 mm, an outer diameter (DO) between 8.65 mm and 30 mm, and an inner diameter; a length to outer diameter ratio between 3:1 and 15:1; and an average Zn-leachability of the inner surface of 0.00085g/cm.sup.2 or less.

2. The container assembly of claim 1, wherein the common material has a compaction of 200m/100 mm or less.

3. The container assembly of claim 1, wherein the common material is selected from a group consisting of a borosilicate glass, an alumino-silicate glass, a cycloolefin copolymer, and a cycloolefin polymer.

4. The container assembly of claim 1, further comprising a plunger in the hollow cylindrical body at the open end.

5. A container assembly for accommodating pharmaceutical compositions, comprising: a container having a hollow cylindrical body with an open end and a closed end opposite to the open end, the closed end being closed by a bottom portion, the hollow cylindrical body and the bottom portion being formed integrally and of a common material, which is a glass or polymer material, the hollow cylindrical body having a length (L) between 35 mm and 120 mm, an outer diameter (DO) between 8.65 mm and 30 mm, and an inner diameter; a length to outer diameter ratio between 3:1 and 15:1; an inner surface of the container having an average Zn-leachability of 0.00085g/cm.sup.2 or less; and a plunger in the open end to sealingly closing the inner surface of the open end to define sealed area, wherein the plunger is pierceable by a cannula and is slidable on the inner surface from the open end towards the closed end.

6. The container assembly of claim 5, wherein the average Zn-leachability is 0.00135g/cm.sup.2 or less.

7. The container assembly of claim 5, wherein the inner surface has an average Mg-leachability of 0.04000g/cm.sup.2 or less.

8. The container assembly of claim 5, further comprising a pressure compliance of at least 0.64 N/mm.sup.2(inner diameter).sup.2.

9. The container assembly of claim 5, wherein the common material has a compaction of 200m/100 mm or less.

10. The container assembly of claim 5, wherein the common material is selected from a group consisting of a borosilicate glass, an alumino-silicate glass, a cycloolefin copolymer, and a cycloolefin polymer.

11. A medical device for expelling or injecting pharmaceutical compositions, comprising: a hollow device body having a cannula; a container assembly inside the hollow device body, the container assembly comprising: a container having a hollow cylindrical body with an open end and a closed end opposite to the open end, the closed end being closed by a bottom portion, the hollow cylindrical body and the bottom portion being formed integrally and of a common material, which is a glass or polymer material, the hollow cylindrical body having a length (L) between 35 mm and 120 mm, an outer diameter (DO) between 8.65 mm and 30 mm, and an inner diameter; a length to outer diameter ratio between 3:1 and 15:1; an inner surface of the container having an average Zn-leachability of 0.00085g/cm.sup.2 or less; and a plunger in the open end to sealingly closing the inner surface of the open end to define sealed area, wherein the plunger is slidable on the inner surface from the open end towards the closed end; and an actuation mechanism that moves the container and the plunger relative to each other and relative to the cannula in a substantially axial direction inside the hollow device body, the container assembly being arranged in the hollow device body so that the cannula pierces the plunger into the sealed area upon movement by the actuation mechanism and applies pressure to the sealed area.

12. The medical device of claim 11, further comprising a pharmaceutical composition in the sealed area.

13. The medical device of claim 11, wherein the common material has a compaction of 200m/100 mm or less.

14. The medical device of claim 11, wherein the common material is selected from a group consisting of a borosilicate glass, an alumino-silicate glass, a cycloolefin copolymer, and a cycloolefin polymer.

15. The medical device of claim 11, wherein the plunger comprises a rubber material having a Zn-leachability of 0.00800g/cm.sup.2 or less.

16. The medical device of claim 11, wherein the average Zn-leachability is 0.00135g/cm.sup.2 or less.

17. The medical device of claim 11, wherein the average Zn-leachability is 0.00055g/cm.sup.2 or less.

18. The medical device of claim 11, wherein the inner surface has an average Mg-leachability of 0.04000g/cm.sup.2 or less.

19. The medical device of claim 11, further comprising a pressure compliance of at least 0.64 N/mm.sup.2(inner diameter).sup.2.

20. The medical device of claim 11, wherein the ratio is between 6:1 and 7:1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0040] For a better understanding of embodiments of the invention and to show how the same may be carried into effect, reference will now be made, by way of example, to the accompanying drawings in which like numerals designate corresponding elements or sections throughout.

[0041] FIG. 1 shows a schematic cross-sectional view of a common prior art container assembly.

[0042] FIG. 2 shows a schematic cross-sectional view of a container assembly according to the present invention.

[0043] FIG. 3 shows a schematic cross-sectional view of a medical device according to the present invention comprising the container assembly of FIG. 2.

DETAILED DESCRIPTION

[0044] Examples of embodiments of the present invention will be explained in more detail by virtue of the following embodiments illustrated in the figures and/or described below.

[0045] FIG. 1 shows a container assembly 10 commonly known from the prior art. The container assembly 10 comprises a container 12 having a body portion with an open end 14 and a closed end 16 opposite to the open end 14. The closed end 16 comprises a neck portion 18 with a reduced diameter and an adjacent flange portion, wherein the flange portion is closed by a metal crimp 20. The container assembly 10 further comprises a plunger 22 that is slidably arranged inside the body portion via the open end 14.

[0046] A pharmaceutical P is accommodated in the body portion of the container 12. For expelling or dispensing the pharmaceutical P from the container 12, a plunger actuation 24 (relative to the container 12) and a fluidic connection 26 are provided on opposite sides of the container assembly 10. Upon actuation, the plunger actuation 24 acts on the container assembly 10 and causes expelling of the pharmaceutical P via the opposite fluidic connection 26. The plunger actuation 24 and the fluidic connection 26 are components of a corresponding medical device (not shown in FIG. 1) and are therefore only schematically illustrated by the arrows 24, 26. The fluidic connection 26 is usually a cannula that before or upon actuation of the medical device pierces through the crimp 20 and a subjacent rubber seal (not shown), which rubber seal is arranged between the crimp 20 and the accommodated pharmaceutical P. The container assembly 10 is installable in the corresponding medical device which is therefore designed in accordance with and dependent on the design and configuration of the container assembly 10.

[0047] FIG. 2 shows a schematic cross-sectional view of a container assembly 100 according to an exemplary embodiment of the present invention. The container assembly 100 comprises container 102 having a hollow cylindrical body with an open end 104 and a closed end 106 opposite to the open end 104. The container assembly 100 further comprises a rubber plunger 108. The rubber plunger 108 is received via the open end 104 in the container 102 and is slidable relative to the hollow cylindrical body from the open end 104 towards the closed end 106.

[0048] The closed end 106 is closed by a bottom portion 110 which is formed integrally with and of the same material as the hollow cylindrical body, i.e. as the lateral surface 112 (shell surface) of the container 102. In the present example, the container 102, more precisely the lateral surface 112 of the hollow cylindrical body and the bottom portion 110 are made of glass, e.g. borosilicate glass. Alternatively, in other embodiments the container 102 can be made of a polymer. The inner surface of the container 102 has an average Zn-leachability of 0.00085g/cm.sup.2 or less.

[0049] In the example shown in FIG. 2, the hollow cylindrical body of the container 102 has a length L of 45 mm, an outer diameter DO of 15 mm and an inner diameter DI of 12 mm, with a length to outer diameter ratio of 3:1. Alternatively, in other embodiments the container 102 may have a length between 35 mm and 120 mm, preferably between 42 mm and 70 mm, an outer diameter between 6.85 mm and 30 mm, preferably between 8.65 mm and 22.05 mm, and an inner diameter between 4.65 mm and 27 mm, preferably between 6.85 mm and 19.05 mm, with a length to outer diameter ratio between 3:1 and 15:1, preferably between 3:1 and 12:1, preferably between 3:1 and 10:1, more preferably between 3:1 and 7:1, more preferably between 4:1 and 7:1, more preferably between 5:1 and 7:1 and more preferably between 6:1 and 7:1.

[0050] A pharmaceutical P is accommodated in the hollow cylindrical body of the container 102. For expelling or dispensing the pharmaceutical P from the container 102, both a plunger actuation 114 (relative to the container 102) and a fluidic connection 116 are realized on the same side of the container 102, i.e. at the open end 104 of the container 102. The plunger actuation 114 and the fluidic connection 116 are components of a corresponding medical device (shown in FIG. 3) and are therefore only schematically illustrated by the arrows 114, 116 in FIG. 2. The fluidic connection 116 can be a cannula that upon actuation of the medical device pierces through the rubber plunger 108. Further, upon and during actuation, the container 102 is moved axially relative to the plunger 108 and the fluidic connection 116.

[0051] By providing the container 102 with a closed end in contrast to the prior art crimp assembly, the neck portion, the flange, the rubber seal and the crimp can be omitted. Thus, the container 102 comprises less components than the prior art assembly and has a more compact size and shape. The dashed area A shown in FIG. 2 represents the overall volume reduction in a corresponding medical device that can be gained by the container 102 according to the present invention compared to the prior art crimp-type container.

[0052] The container assembly 100 is installable in a medical device. A medical device 120 according to an exemplary embodiment of the present invention is schematically shown in FIG. 3. The medical device 120 comprises a hollow device body 122 (a device housing), in which the container assembly 100 and further components of the medical device 120 are housed. Same reference signs are used throughout the figures for the same or mutually corresponding elements and features.

[0053] As shown in FIG. 3 the fluidic connection 116 is a cannula that pierces through the plunger 108 and extends with a first end 116A into the hollow cylindrical body of the container 102. An opposite second end of the cannula is fluidically connected to a tube 124 for expelling the pharmaceutical P accommodated in the container 102 via the cannula and the tube 124. The tube 124 can be fluidically connected to further components of the medical device 120 or a connected device.

[0054] In the example of FIG. 3, the plunger actuation 114 relative to the container 102, more precisely the movement of the container 102 relative to the plunger 108 is realized by the actuation mechanism 126. The actuation mechanism 126 comprises a spring 128, which in an initial position (unactuated state) is preloaded. The actuation mechanism 126 further comprises a trigger 130. Upon actuation of the medical device 120 by operating the trigger, the spring 128 applies force to and thus moves the container 102 relative to the plunger 108 and relative to the cannula 116. The plunger 108 and the cannula 116 maintain stationary during actuation and use of the medical device 120. By moving the container 102 relative to the stationary plunger 108, the plunger 108 applies pressure to the accommodated pharmaceutical P, which is thus expelled via the cannula 116 and the fluidically connected tube 124.

EXAMPLE

[0055] For analyzing the average leachability by means of ICP-MS, portions of test and control extracts can be prepared in suitable plastic containers and can be acidified to approximately 2% with concentrated nitric acid. The resulting solutions can be analyzed with the following method and instrumental parameters:

TABLE-US-00002 TABLE 1 ICP-MS; Instrumental Parameters Timing Parameters Sweeps/Readings 20 Readings/Replicate 1 Number of Replicates 3 Signal Processing Detector Mode Dual AutoLens On Spectral Peak Processing Average Signal Peak Processing Average Blank Subtraction after internal standard Pump Parameters Sample Analysis Speed 24 mL/ min Sample Flush Time 80-120 sec Sample Flush Speed 48 mL/min Read Delay Time 30-45 sec

TABLE-US-00003 TABLE 2 ICP-MS; Ion Mass Used for Analysis Element Mass Mg 24 Al 27 Zn 66

[0056] Based on the above method and instrumental settings and parameters, an ICP-MS analysis has been conducted. The purpose of this analysis was to perform a chemical characterization of a glass container according to an embodiment of the invention. Per ISO 10993-18:2009, the chemical characterization information generated was used for measurement of the level of a leachable substance in a medical device in order to allow the assessment of compliance with the allowable limit derived for that substance from health based risk assessment (ISO 10993-17:2009).

[0057] This analysis was conducted based on ISO 10993-18, Biological evaluation of medical devicesPart 18: Chemical characterization of materials. The analysis was performed in compliance with the ISO 13485:2016 standard.

[0058] The test article was prepared based on a surface area of 27.4 cm.sup.2 for one glass cartridge. Only the glass cartridge was included in the preparation. The plunger was removed. The test article was not subdivided.

[0059] The analytical extraction was prepared according to TABLE 3:

TABLE-US-00004 TABLE 3 Analytical Extraction Volume Article Pieces of of Final Extraction Amount Test Vehicle Extraction Number Volume Vehicle Ratio (cm.sup.2) Article (mL) Condition of Cycles (mL) Purified 3 cm.sup.2:1 mL 54.8 2 18 50 C. 1 18 Water for 72 Extraction hours prepared in a suitable plastic container for ICP- MS testing.

[0060] System suitability standards were prepared in 2% nitric acid and diluted to result in final concentrations of 10, 250, 500 and 750 ng/mL. These standard solutions were analyzed and the resulting responses evaluated for system suitability criteria prior to examining the test extract results.

[0061] Portions of the test and control extracts prepared in suitable plastic containers were acidified to approximately 2% with concentrated nitric acid. The resulting solutions were analyzed with the above method and instrumental parameters.

[0062] The same ICP-MS analysis was performed for a commercially available prior art glass container with the structural configuration shown in FIG. 1.

[0063] A comparison of the measured values of the glass container according to the invention and the commercially available prior art glass container is shown in the TABLE 4 below.

TABLE-US-00005 TABLE 4 comparison of test results for a glass container of the invention and a prior art glass container Zn-leachability Mg-leachability Al-leachability g/test article g/test article g/test article glass container <0.00400 <0.00400 <0.00400 according to the invention prior art glass 0.02580 0.41100 ./. container

TABLE-US-00006 LIST OF REFERENCE SIGNS P pharmaceutical 10 container assembly (prior art) 100 container assembly 12 container (prior art) 102 container 14 open end (prior art) 104 open end 16 closed end (prior art) 106 dead end 18 neck portion (prior art) 108 plunger 20 crimp (prior art) 110 bottom portion 22 plunger (prior art) 112 lateral surface 24 plunger actuation (prior art) 114 plunger actuation 26 fluidic connection (prior art) 116 fluidic connection (cannula) 116A first end of the cannula 116B second end of the cannula L length DO outer diameter DI inner diameter 120 medical device 122 hollow device body (device housing) 124 tube 126 actuation mechanism 128 spring 130 trigger