Abstract
The present invention relates to a testing device for testing the moving force of a plunger of a syringe, comprising a fixture, FX, (3) for holding a syringe (8) in the testing device, TD, (1) for moving force testing, wherein the fixture (3) comprises an annular holding element, AHE, (5) for holding part of the syringe (8), and a support frame, SF, (30) having a support plate, SP, (300) for supporting the annular holding element, AHE, (5), wherein the annular holding element, AHE, (5) is detachably connected to the support plate, SP, (300) via an indirect connection via at least one intermediate element, IE, (10) between the at least one annular holding element, AHE, (5) and the support plate, SP, (300), wherein one intermediate element, IE, (10) is a tempering cylinder, TC, (7) for tempering at least part of the syringe (8). The invention further relates to a method for testing the moving force of a plunger of a syringe.
Claims
1. A testing device for testing the moving force of a plunger of a syringe, comprising a load frame and a fixture, FX, for holding a syringe in the testing device, TD, for moving force testing, wherein the fixture comprises an annular holding element, AHE, for holding part of the syringe, and a support frame, SF, having a support plate, SP, for supporting the annular holding element, AHE, wherein the annular holding element, AHE, is detachably connected to the support plate, SP, via an indirect connection via at least one intermediate element, IE, between the at least one annular holding element, AHE, and the support plate, SP, wherein one intermediate element, IE, is a tempering cylinder, TC, for tempering at least part of the syringe.
2. The testing device according to claim 1, wherein the at least one annular holding element, AHE, is a flange holder, FH, for holding the flange of the syringe.
3. The testing device according to claim 1, wherein the at least one annular holding element, AHE, is a needle holder, NH, for holding the needle cannula, NC, or Luer cone, LC, of the syringe.
4. The testing device according to claim 1, wherein the at least one annular holding element, AHE, is a receiving cylinder, RC, for receiving the barrel of the syringe to be held in the fixture, FX.
5. The testing device according to claim 1, wherein the fixture, FX, comprises at least two annular holding elements, AHEs, which are a flange holder, FH, and a needle holder, NH.
6. The testing device according to claim 1, wherein the fixture, FX, comprises at least three annular holding elements, AHEs, which are a flange holder, FH, a receiving cylinder, RC, and a needle holder, NH.
7. The testing device according to claim 1, wherein there is only one intermediate element, IE, wherein the only one intermediate element, IE, functions both as a tempering element and as a distance element.
8. The testing device according to claim 1, wherein there are two or more intermediate elements, IE, the function of at least one of the two ore more intermediate elements, IE, comprises the function of a tempering element; and the function of at least a second of the two or more intermediate elements, IE, comprises the function of a distance element.
9. Tho testing device according to claim 1, wherein there are two or more intermediate elements, IE, and at least one of the two or more intermediate elements, IE, is a tempering cylinder, TC; and at least a second of the two or more intermediate elements, IE, is a spacer.
10. The testing device according to claim 5, wherein the annular holding elements, AHEs, are directly attached to one another or indirectly attached via at least one intermediate element, IE, which is a spacer.
11. The testing device according to claim 1, wherein the tempering cylinder, TC, is adapted for receiving an annular holding element of the at least one annular holding element, AHE, in the form of a receiving cylinder, RC, for receiving the barrel of the syringe inserted into the inner diameter of the tempering cylinder, TC.
12. The testing device according to claim 1, wherein the tempering cylinder, TC, is adapted for receiving an annular holding element of the at least one annular holding element, AHE, which is a needle holder, NH, for receiving the needle cannula, NC, of the syringe and an annular holding element, AHE, which is a flange holder, FH, and the testing device, TD, comprises a spacer.
13. The device according to claim 1, wherein the testing device, TD, comprises at least two temperature sensors and the at least one annular holding element, AHE, has at least two measuring holes for insertion of a temperature sensor.
14. The testing device according to claim 1, wherein the load frame is a load frame for applying pressure on the plunger of a syringe held in the fixture of the testing device and for measuring the force for moving the plunger.
15. The testing device according to claim 1, wherein the at least one annular holding element, AHE, is made of metal.
16. A method for testing the moving force of a syringe, wherein the method is carried out with a testing device according to claim 1.
17. The method according to claim 16, wherein the method comprises the steps a) setting the temperature in at least part of the syringe via the tempering cylinder TC, b) applying a pressure on the plunger of the syringe via a load frame, c) measuring the force for moving the plunger in the syringe via the load frame.
18. The method according to claim 17, wherein the method comprises step d) monitoring the temperature present in at least part of the syringe via at least one temperature sensor.
19. The method according to claim 17, wherein the method comprises the step e) monitoring the temperature in the vicinity of the barrel, in the vicinity of the needle cannula, NC, or Luer cone, LC, or at the inside of the barrel.
20. The method according to claim 17, wherein the method comprises the step f) adjusting the temperature of at least part of the syringe.
21. A fixture kit for a fixture, FK, for holding a syringe in a testing device, TD for testing the moving force of a plunger of a syringe, comprising a load frame and the fixture, FX, for moving force testing, wherein the fixture comprises an annular holding element, AHE, for holding part of the syringe, and a support frame, SF, having a support plate, SP, for supporting the annular holding element, AHE, wherein the annular holding element, AHE, is detachably connected to the support plate, SP, via an indirect connection via at least one intermediate element, IE, between the at least one annular holding element, AHE, and the support plate, SP, wherein one intermediate element, IE, is a tempering cylinder, TC, for tempering at least part of the syringe wherein the fixture kit comprises the at least one support frame, SF, and the at least two annular holding elements, AHEs.
22. The fixture kit according to claim 21, wherein the fixture kit comprises the at least two annular holding elements, AHEs, wherein each annular holding elements, AHE, has an axial through hole and the inner diameter of the axial through hole of the at least two annular holding elements, AHEs, is different.
23. The Fixture kit according to claim 21, wherein the fixture kit comprises the tempering cylinder, TC.
24. The Fixture kit according to claim 23, wherein the TC is a TC for adjusting the temperature of a part of the syringe.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0114] The present invention will be described again with reference to the enclosed drawings, wherein:
[0115] FIG. 1: shows a schematic perspective view of a first embodiment of the fixture according to the invention;
[0116] FIG. 2: shows a schematic view of one type of a syringe, syringe with a NC and a needle shield;
[0117] FIG. 3: shows a schematic view of another type of a syringe, syringe with a LC and a tip cap;
[0118] FIG. 4: shows a perspective view of the upper components of the embodiment of the fixture of FIG. 1;
[0119] FIG. 5: shows a perspective view of the upper components of the embodiment of the fixture of FIG. 1;
[0120] FIG. 6: shows a perspective view of the lower components of an embodiment of the fixture according to the invention;
[0121] FIG. 7: shows a perspective view of a second embodiment of the fixture according to the invention;
[0122] FIG. 8: shows a schematic sectional view of the support frame of the second embodiment of the fixture according to FIG. 7;
[0123] FIG. 9: shows a schematic view of an embodiment of the fixture kit according to the invention;
[0124] FIG. 10: shows a schematic sectional view of a first embodiment of a testing device according to the invention;
[0125] FIGS. 11, 12, 13: show perspective views of a first embodiment of a receiving cylinder of the testing device according to FIG. 10;
[0126] FIGS. 14, 15: show perspective bottom views of a first embodiment of a receiving cylinder of the testing device according to FIG. 10;
[0127] FIGS. 16, 17: show perspective views of the first embodiment of a testing device according FIG. 10 during assembly;
[0128] FIG. 18: shows a perspective view of the first embodiment of a testing device according FIG. 10 after assembly;
[0129] FIG. 19: shows a perspective bottom view of the first embodiment of a testing device according FIG. 10 after assembly;
[0130] FIGS. 20 and 21: shows perspective views of embodiment of temperature sensors of the testing device according to the invention;
[0131] FIG. 22: shows a schematic sectional view of a second embodiment of a testing device according to the invention;
[0132] FIGS. 23, 24, 25: show perspective views of receiving cylinder with needle holder of the second embodiment of the testing device according to FIG. 22;
[0133] FIG. 26: shows a sectional view of the needle holder of the second embodiment of the testing device according to FIG. 22;
[0134] FIGS. 27, 28: show perspective views of the second embodiment of the testing device according FIG. 22 during assembly;
[0135] FIG. 29: shows a schematic sectional view of a third embodiment of a testing device according to the invention;
[0136] FIGS. 30, 31: show perspective views of a needle holder of the third embodiment of the testing device according FIG. 22 during assembly;
[0137] FIG. 32: shows a perspective view of the needle holder of the third embodiment of the testing device according FIG. 22;
[0138] FIG. 33: shows a perspective view of the third embodiment of the testing device according FIG. 22 with a syringe;
[0139] FIGS. 34-37: show perspective views of the third embodiment of the testing device according FIG. 22 during assembly;
[0140] FIGS. 38, 39: show perspective views of the third embodiment of the testing device according FIG. 22 after assembly;
[0141] FIGS. 40-43: show graphs of moving force values
[0142] FIG. 44a: show a schematic sectional view of a fourth embodiment of the testing device;
[0143] FIGS. 44b and 44c: show schematic side views of an auto-injector for a syringe.
[0144] FIG. 45a: shows a schematic sectional view of a fifth embodiment of the testing device;
[0145] FIG. 45b shows a schematic side view of an embodiment of an auto-injector syringe;
[0146] FIG. 46a shows a schematic sectional view of a sixth embodiment of the testing device with a passive safety guard; and
[0147] FIG. 46b shows a schematic perspective view of an embodiment of a passive safety guard syringe.
DETAILLED DESCRIPTION OF PREFERRED EMBODIMENTS
[0148] The present invention will now be described in more detail with reference to the enclosed figures. Same components and arrangements are denoted in the figures by the same reference numerals and the respective description may be omitted in order to avoid redundancies.
[0149] Features and advantages which are described with respect to the fixture also apply to fixture kit, the testing devices and the method for testing and vice versa and are only described once.
[0150] In FIG. 1 a schematic perspective view of a first embodiment of the fixture 3 according to the invention is shown. In the depicted embodiment, the fixture 3 comprises a SF 30. The SF 30 consists of a SP 300, a CP 302 and two poles 301 extending therebetween. The poles 301 can be firmly attached to the SP 300 and the CP 302 for example by welding, or they can be attached by a screw-type connection. The SP 300 is the upper plate of the SF 30 and the CP 302 is the lower plate. On the CP 302 a tray 3020 is mounted. The tray 3020 has a circular shape and a circular rim for holding a beaker. At the bottom of the CP 302 a foot 303 extends downwardly. In the SP 300 an aperture 3000 is provided in the middle. The aperture 3000 has an inner thread 3001. The aperture 3000 serves for receiving an AHE 5. In the first embodiment of the fixture 3 shown in FIG. 1, the AHE 5 is a FH 50. In FIG. 1 only the head 501 of the FH 50 can be seen. At the outer circumference of the head 501 recesses are provided for facilitating gripping of the head 501 and screwing of the FH 50. The FH 50 has a through hole 502 extending over its entire height. The through hole 502 serves for receiving the barrel 80 of a syringe 8 to be held in the fixture 3. The syringe 8 can have the design as shown in FIG. 2 as described herein. The plunger 81 of the syringe 8 will be moved in the TD 1, which will be described later, by a post 21, which can be attached to a load frame 2 (see FIG. 7).
[0151] In FIG. 4 the FH 50 is shown with the barrel 80 of the syringe 8 inserted into the through hole 502 of the FH 50. The FH 50 has a body 500 extending downward from the head 501. The body 500 has a smaller out diameter than the head 501. The inner diameter of the body 500 can be larger than the through hole 502 at the head 501. Thereby a collar 504 (see FIG. 29) is formed. An outer thread 503 is provided on the outer circumference of the body 500. The height of the body 500 corresponds to the thickness of the SP 300. As can be derived from FIG. 4, the flange 801 of the barrel 80 rests on the upper side of the head 501 of the FH 50 while the barrel 80 extends through the through hole 502 and protrudes over the bottom end of the FH 50, in particular the bottom end of the body 500 of the FH 50.
[0152] FIG. 5 shows the FX 3 with the FH 50 screwed into the aperture 3000 of the SP 300 and with the barrel 80 of the syringe 8 inserted into the through hole 502 of the FH 50. In this state, the plunger 81 can be inserted into the barrel 80 and the SCS 83 can be removed. Once the FX 3 is mounted in a load frame 2, the plunger 81 can be pushed down by the post 21. The force necessary for moving the plunger 81 will be measured. If the syringe 8 is a PFS, the liquid contained in the volume of the syringe 8 will be dispensed via the dispensing opening 82 of the syringe 8 into the beaker sitting on the tray 3020 of the fixture 3.
[0153] FIG. 6 shows how the FX 3 can be attached to the load frame 2. The foot 303 of the SF 30 is attached to a protrusion of a connecting disc 22. The protrusion is arranged in the middle of the connecting disc 22. The connecting disc 22 is attached to the base 20 of the load frame 2 by screws.
[0154] In FIG. 7 a second embodiment of the FX 3 according to the invention is shown. The second embodiment differs from the first embodiment in that the SP 300 is attached to the poles 301 of the SF 30 by screws. In addition, in the second embodiment, an IE 10, in particular a TC 7 is mounted to the SP 300. The TC 7 may be attached to the top side of a SP 300 of FIG. 1. This position of the TC 7 is indicated in FIG. 8 with the dashed line. The tempering room 700 within the TC 7 in that case is aligned with the aperture 3000 of the SP 300. Preferably, the TC 7 is, however, received in a large mounting opening in the SP 300 and extends through the mounting opening with the bottom of the TC 7 being in the same plane as the bottom side of the SP 300 (see FIG. 8). As will be described in further detail below, the second embodiment of the FX 3 also differs from the first embodiment by the AHE 5 used to hold the syringe. The AHE 5 of the second embodiment is a RC 51. The RC 51 is attached to the TC 7 by insertion of the RC 51 into the tempering room 700 of TC 7. Thereby an indirect connection between the AHE 5 and the SP 300 is provided with IE 10 which is the TC 7.
[0155] As can be derived from FIG. 8 which shows a schematic sectional view of the support frame 30 of the second embodiment of the FX 3, the TC 7 has an annular wall 70. The annular wall 70 encloses the tempering room 70 which extends over the entire height of the TC 7. In the wall 70 a channel (not shown) for tempering medium is provided. The tempering medium is provided to the TC 7 via a connector 71 (see FIG. 9) and exits from the TP 7 via another connector 71. The temperature of the tempering medium is set and can be adjusted at a heating/cooling unit (not shown). The TC 7 is connected to the heating/cooling unit preferably via tubes which are attached to the connectors 71. At the upper section of the tempering room 700 an inner thread 701 is provided at the circumference. The inner diameter of section with the inner thread 701 is larger than the inner diameter of the tempering room 700.
[0156] In FIG. 10 a first embodiment of a TD 1 according to the invention is shown. In FIG. 10 only the TC 7 with the AHE 5 and the SP 300 of the TD 1 is shown. In this first embodiment, an AHE 5 which is a RC 51 is inserted into the tempering room 700. As can be seen in FIG. 11, the RC 51 has a head 511 and a body 510 extending from the bottom of the head 511. The head 511 has a larger diameter than the body 510. At the upper section of the body 510 an outer thread 513 is provided. The section with the outer thread 513 has a larger diameter than the remaining part of the body 510. The outer diameter of the section of the body 510 with the outer thread 513 corresponds to and preferably is equal to the inner diameter of the section of the tempering room 700 with the inner thread 701. The outer diameter of the part of the body 510 without the outer thread 513 corresponds to the inner diameter of the tempering room 700 and preferably is equal to the inner diameter of the tempering room 70. Thereby, the outside surface of the part of the body 510 of the RC 51 without the outer thread 513 is in close contact with the inner side of wall 70 of the TC 7 and the temperature set by the tempering medium in the wall 70 of the tempering room 700 of the TC 7 can be conveyed to the RC 51.
[0157] The length of the RC 51 corresponds to and preferably is equal to the height of the TC 7.
[0158] The RC 51 has a through hole 512. The inner diameter of the through hole 512 in the upper section is larger than in the lower section. This can be best seen in FIG. 12. In the upper section the plunger 81 of the syringe 8 to be held in the FX 3 of the TD 1 is located. The inner diameter of the upper section is larger than the diameter of the post 21 of the load frame 2, which is to apply force onto the plunger 81. The length of the lower section corresponds to the length of the barrel 80 of the syringe 8 to be held in the fixture 3 of the TD 1. The inner diameter of the lower section of the through hole 512 corresponds to the outer diameter of the barrel 80 and preferably is equal to the outer diameter of the barrel 80. The flange 801 of the barrel 80 rests on the step 516 formed by the different diameters of the upper and the lower section of the through hole 512. The NC 820 extends over the bottom end of the through hole 512. This is shown in FIGS. 14 and 15.
[0159] In the RC 51 of this embodiment two measuring holes 514 are provided. The measuring holes 514 extend from the bottom end of the RC 51 in the axial direction. The position of the measuring holes 514 can be best seen in FIG. 13. The length of the measuring holes 514 correspond to the length of the lower section of the RC 51. The measuring holes 514 are parallel to the through hole 512 and in the mounted condition of the RC 51 in the TC 7 are positioned between the inner side of the wall 70 and the through hole 512 of the RC 51. Temperature sensors (not shown) are inserted into the measuring holes 514 from the bottom.
[0160] The RC 51 can be inserted into the tempering room 700 of the TC 7 as shown in FIGS. 16 and 17. In these figures, the syringe 8 is already inserted into the RC 51. Preferably, the syringe 8 will however only be inserted into the RC 51 once it is inserted and attached to the TC 7. Once the RC 51 is received in the tempering room 700 it will be attached to the wall 70 of the TC 7 by screw-type connection between the outer thread 513 of the RC 51 and the inner thread 701 of the TC 7.
[0161] FIG. 18 shows the RC 51 in the mounted position in the TC 7. As can be derived from FIG. 19, the NC 820 which is covered in FIG. 19 with the SCS 83, extends over the bottom surface of the TC 7.
[0162] With the first embodiment of the TD 1 as shown in FIGS. 10 to 19 the temperature of the barrel 80 of the syringe 8 can be set and adjusted by the TC 7. The temperature and any temperature changes can be monitored by sensors which are introduced into the measuring holes 514 of the RC 51.
[0163] FIGS. 20 and 21 show a sensing unit 9 and sensors 90, 91, 92 to be used in the TD 1. In FIG. 20 two sensors 90, 91 have been inserted into the measuring holes 514 of the RC 51. In FIG. 21, a third sensor is introduced into the barrel 80 of the syringe 8. By using three sensors 90, 91, 92, the temperature of the barrel 80 and of the inside of the barrel 80 can be measured, verified and adjusted. In particular, a first sensor 91 is connected to the heating/cooling unit and serves for controlling the heating/cooling unit. Second sensor 90 is an external sensor, that means is not connected to the heating/cooling unit. The second sensor 90 servers for measuring the actual temperature and thus for confirming that the temperature set at the heating/cooling unit is reached at the RC 51. The third sensor 92 serves for measuring the temperature within the barrel 80. In particular, the third sensor serves for measuring the temperature of a liquid in the barrel. By using this third sensor, any difference between the temperature measured by the second sensor 91 and the third sensor 92 can be taken into account when measuring the temperature during a moving force test with the TD 1, and can also be used for adjustment of the temperature of the heating/cooling unit.
[0164] These sensors 90, 91, 92 can be used for any embodiment of the TD 1.
[0165] In FIG. 22 a second embodiment of the TD 1 is shown. In FIG. 22 only the TC and the AHEs 5 of the TD 1 are shown. This embodiment differs from the first embodiment by the layout of the RC 51. The RC 51 of the second embodiment differs from the RC 51 of the first embodiment as shown in FIGS. 10 to 19 only in that the inner diameter of the through hole 512 is continuous over the length of the through hole 512 and that a further AHE 5 is inserted into the bottom of the RC1 via screw-type connection. For this purpose, an inner thread 515 is provided at the lower section of the through hole 512 of the RC 51.
[0166] The inner diameter of the through hole 512 of the RC 51 of the second embodiment corresponds to and preferably is equal to the outer diameter of the barrel 80 of the syringe 8 to be held in the TD 1.
[0167] The additional AHE 5 which is inserted into the through hole 512 from the bottom is a NH 52 in the form of a threaded bush 521. The threaded bush 521 has a body 5210 and a head 5211, the latter is in the mounted position at the bottom of the threaded bush 521. The body 5210 has an outer thread 5213. The outer diameter of the body 5210 corresponds to the inner diameter of the lower part of the through hole 512 of the RC 51. The threaded bush 521 has a through hole 5212, which extends over the entire length of the threaded bush 521.
[0168] As can be best seen in FIG. 26, which shows the end of the body 5210 of the threaded bush 521 opposite to the head 5211, the inner diameter of the through hole 5212 is smaller at that end than over the remaining part of the body 5210. In particular, at the end opposite the head 5211, an insert 5214 in form of a bush is provided in the threaded bush 521. The insert 5214 has a cylindrical shape, wherein the inner diameter of the insert 5214 forms the through hole 5212 and the outer diameter is received in a recess 5215 provided in the end of the threaded bush 521 opposite the head 5211. The inner diameter of the insert 5214 corresponds the outer diameter of the NC 820. Here the NC 820 is received. These two equal diameters provide for a transmission of the temperature of the TC 7 to the NC 820. If no threaded bush is inserted into the RC 51, only the temperature of the barrel which is received in the RC 51 can be adjusted. The inner diameter of the threaded bush 521 in the section adjacent to the recess 5215 in the direction towards the head 5211 is smaller than the diameter of the recess 5215. Thereby a step is formed and the axial end of the insert 5214 which is received in the recess 5215 abuts on the step.
[0169] The threaded bush 521 is inserted into the through hole 512 of the RC 51 from the bottom. As can be seen in FIG. 25, the head 5211 of the threaded bush 521 faces downwards. The RC 51 with the threaded bush 521 can be inserted into the TC 7 as shown in FIG. 28. The syringe 8 can be inserted into the through hole 512 of the RC 51 as shown in FIG. 27 and the flange 801 of the syringe will rest on the upper side of the head 511 of the RC 51. The insert 5214 of the threaded bush 521 with the through hole 5212 formed therein, faces upwards. Thereby the NC 820 of the syringe 8 can enter the insert 5214.
[0170] With the second embodiment, the temperature of both the barrel 80 and the NC 820 of the syringe 8 can be adjusted. The temperature from the TC 7 will be transferred to the RC 51, wherein the barrel 80 is positioned. The RC 51 will transfer this temperature to the threaded bush 521 which is inserted into the RC 51 and thereby to the NC 820.
[0171] In FIG. 29 a third embodiment of the TD 1 is shown. This embodiment differs from the first and second embodiment of the TD 1 in that instead of a RC 51 a different AHE 5 is inserted into the tempering room 700 of the TC 7. In the third embodiment, the AHE 5 which is inserted into the TC 7 is a NH 52 in the shape of a disc body 520.
[0172] As can be best seen in FIG. 31, the disc body 520 has a head 5201 and a body 5200 extending from the bottom of the head 5201. The diameter of the head 5201 is larger than the outer diameter of the body 5200. In the upper section of the body 5200 adjacent to the head 5201 an outer thread 5203 is provided on the circumference of the body 5200. The disc body 520 has an axial through hole 5202 which extends over the entire height of the disc body 520. As can be derived the inner diameter of the through hole 5202 is smaller in the area of the head 5201 and upper section of the body 5200 and larger towards the lower end of the body 5200. The inner diameter of the through hole 5202 at the head 5201 of the disc body 520 corresponds to and preferably is equal to the outer diameter of the NC 820. A NC 820 inserted into the through hole 5202 is shown for example in FIG. 32.
[0173] The disc body 520 is inserted into the tempering room 700 of the TC 7, which is a first IE 10, and is attached to the wall 70 by screw-type connection between the outer thread 5203 of the disc body 520 and the inner thread 701 of the TC 7. This is shown in FIGS. 30 and 31.
[0174] When inserted into the TC 7, the head 5201 of the disc body 520 extends over the upper surface of the TC 7, in particular the upper surface of the wall 70. This is for example depicted in FIG. 33. According to the third embodiment of the TD 1 a second IE 10, in particular a spacer 6 is provided over the disc body 520. The spacer 6 is formed by a cylindrical wall 60. At the bottom of the wall a receiving recess 61 is provided for receiving the head 5201 of the disc body 520. In the upper section of the wall 60 an inner thread 62 is provided at the inner circumference of the wall 60. Thereby, a FH 50 can be inserted into the upper end of the spacer 6. The FH 50 is a FH as described above with reference to the first embodiment of the fixture 3. The FH 50 is attached to the spacer 6 by screw-type connection between the outer thread 503 of the FH 50 and the inner thread 62 of the spacer 6. The spacer 6 may be made of a material of low heat transfer coefficient. For example, the spacer 6 may be made of plastic.
[0175] The spacer 6 has an inlet 64 and an outlet 65 for air. The inlet 64 and outlet 65 are provided in the wall 60 in the lower section. The inlet 64 may be connected to a tube 63 for input of airflow to the inside of the spacer 6. The inlet 64 and outlet 65 are arranged in such a distance from the bottom of the spacer 6, that they are at a height corresponding to the shoulder 803 of the syringe 8, which is inserted into the disc body 520. As can be seen in FIGS. 32 and 33, the syringe 8 is inserted into the disc body 520, in particular into the through hole 5202 of the disc body 520 only with the NC 820. Thereby, the temperature of only the NC 820 will be adjusted by the TC 7. The barrel 80 of the syringe is above the TC 7 and is thus not affected by the temperature set in the TC 7. As temperature convection may however occur from the upper side of the disc body 520 to the inside of the spacer 6, the air passing through the inlet 64 and outlet 65 is used to shield the barrel 80 from this temperature convection.
[0176] Once the spacer 6 is placed on the head 5201 of the disc body 520 and the FH 50 is screwed into the spacer 6 at the top, the syringe 8 can be inserted. The attachment of disc body 520 and FH 50 with the spacer 6 is shown in FIGS. 34 to 37. As shown in FIGS. 38 and 39 the syringe 8 is inserted with its barrel 80 into the FH 50 and the flange 801 rests on the collar 504 of the FH 50. In this position, the NC 820 is inside the through hole 5202 of the disc body 520. The through hole 5202 may be formed at least partially by an insert (not shown) corresponding to the insert 5214 of the threaded bush 521 described above.
[0177] Two measuring holes 5204 are provided in the bottom of the disc body 520 (see FIG. 29). In these measuring holes 5204 sensors 90, 91 as described above may be inserted from the bottom. The measuring holes 5204 extend from the bottom of the disc body 520 to a level close to the top of the head 5201 of the disc body 520.
[0178] The different embodiments of the fixture 3 and the TD 1 as described above can be realized with a fixture kit. One embodiment of such a fixture kit is shown in FIG. 9. The kit comprises the components of the SF 30, in particular a SP 300, a CP 302 and poles 301. In addition, the kit comprises at least two different AHEs 5. In the depicted embodiment, the AHEs are RCs 51, and NHs 52. The respective AHEs 5 thus differ in design. In addition, the AHEs differ in geometry. In particular, two NHs 52 in the form of disc bodies 520 are provided, wherein each disc body 520 has a through hole 5202 of a different diameter. These AHEs are used for the third embodiment of the TD1 as described above, i.e. for tempering the NC 820 of the syringe 8 only. Due to the different diameters of the through holes 5202, the appropriate NH 52 can be selected depending on the diameter of the NC 820 of the syringe 8 to be held. For example, NCs of sizes 25G or 27G may be tested.
[0179] The RCs 51 differ in that three are shown to have a wider diameter in the upper section of the through hole 512. These RCs 51 shown at the upper left of FIG. 9 are used for the first embodiment of the TD 1 described above, that means for tempering the barrel 80 of the syringe 8 only. The additional three RCs 51 shown at the upper right of FIG. 9 are RCs 51 with a continuous diameter of the through hole 512 and are adapted to receive a NH 52 in the form of a threaded bush 521 at its lower end. These RCs 51 are thus used for the second embodiment of the TD 1 as described above, i.e. for tempering both the NC 820 and the barrel 80 of the syringe.
[0180] The RCs 51 of each kind are provided in the kit with three different diameters of the through hole 512. Thereby, the appropriate RC 51 can be selected depending on the diameter of the syringe 8 to be held. For example, syringes with a volume of 0.5 ml, 1 ml or 2.25 ml may be tested.
[0181] In addition to the elements of the kit shown in FIG. 9, the kit can further comprise a spacer and at least one and preferably several FHs 50 with different diameter of the through hole 502.
[0182] The SP 300 shown in FIG. 9 is a SP 300 with a TC 7 affixed to it. The kit can further comprise a SP 300 as shown in FIG. 1 without TC 7 and with an aperture 3000 for receiving a FH 50.
[0183] In FIGS. 40 to 43 graphs showing test results of moving force tests which were conducted with a TD 1 according to the invention are depicted.
[0184] In the test, the force required to empty a glass syringes at 100 mm/min was measured at 4 different temperatures, namely at: 0° C., 5° C., 25° C. and 60° C. The size of the NC of the syringes used was 29 G (Gauge). The waiting period between measurements was 10 min.
[0185] In the tests of FIG. 40, the syringe was filled with motor oil 10W40. As can be derived from FIG. 40 the force which was measured over the distance by which the plunger has moved, was higher for lower temperatures. The measured force is the moving force which is necessary to move the plunger.
[0186] In the tests of FIG. 41, the syringe was filled with His buffer. The His buffer contained: 160 g of BSA (bovine serum albumin) 80 mg/ml, 6 g of PS80 (Polysorbate 80) 10%, 170 g of sucrose 85 mg/ml. His Buffer made of 3.104 g L-Histidine, 4.192 g Histidine Monohydrochloride, 2000 ml water and some HCl in order to reach a pH 6.0 was used to bring the final volume of the solution (2000 ml). Also in this graph it is obvious that the higher the temperature, the lower the required moving force.
[0187] In the tests of FIG. 42, the syringe was filled with water. Also in this graph it is obvious that the higher the temperature, the lower the required moving force.
[0188] In FIG. 43 the test results for moving tests carried out at 25° C. with syringes filled with different liquids are compared. The difference of required force becomes obvious from this graph.
[0189] In FIG. 44a a schematic view of a fourth embodiment of the testing device 1 is shown. In FIG. 44a only the TC 7 and the AHEs 5 of the TD 1 are shown. This embodiment differs from the first embodiment by the layout of the RC 51. The RC 51 of the fourth embodiment differs from the RC 51 of the first embodiment as shown in FIGS. 10 to 19 in that the RC 51 according to the fourth embodiment is a two-part RC 517. The two-part RC 517 consists of an upper part 5170 and a lower part 5171. The upper part 5170 comprises a ring section 51700 and a tubular section 51701 extending from the bottom of the ring section 51700. The ring section 51700 has a larger outer diameter than the tubular section 51701. The ring section 51700 has an outer thread (not shown) for screw-type connection with the inner thread (not shown in FIG. 44a) of the TC 7. The tubular section 51701 extends into the tempering room 700 of the TC 7.
[0190] The lower part 5171 comprises a ring section 51710 and a tubular section 51711 extending from the top of the ring section 51710. The ring section 51710 has a larger outer diameter than the tubular section 51711. The ring section 51710 has an outer thread (not shown) for screw-type connection with an inner thread (not shown) in the lower part of the tempering chamber 700 of the TC 7. The tubular section 51711 extends into the tempering room 700 of the TC 7.
[0191] At the inner diameter of the lower part 5171 in a lower section, in particular in the vicinity or at the upper end of the ring section 51710, a step 51712 is provided. Thereby the inner diameter in the ring section 51710 is smaller than in the tubular section 51711. In the tubular section 51711 a tapered section 51714 is formed. This tapered section 51714 is preferably formed by two recesses 51713 which are formed in the inner diameter of the tubular section 51711 at diametrical opposite positions. The inner diameter of the tubular section 51711 in the angle range of the recesses 51713 is larger than the inner diameter of the tubular section 51701 of the upper part 5170. In the angle range where no recesses are provided, the inner diameter of the tubular section 51711 can be equal to the inner diameter of the upper part 5170. In the depicted embodiment the inner diameter of the tubular section 51701 and the inner diameter of the ring section 51700 of the upper part 5170 are equal.
[0192] The length of the tubular section 51701 of the upper part 5170 is shorter than the length of the tubular section 51711 of the lower part 5171.
[0193] In FIG. 44a it is shown that an auto-injector syringe 84 is inserted into the two-part RC 517.
[0194] One embodiment of the auto-injector syringe 84 is shown in FIGS. 44b and 44c. The auto-injector syringe 84 has a tubular casing 840 with a cap 841 movably received in the tubular casing 840 at the distal end of the tubular casing 840. The syringe is received in the tubular casing 840. In particular, the barrel, the plunger and the NC are surrounded by the tubular casing. At the top of the casing a head 842 is provided, which serves for activating the injection and dispensing the fluid from the syringe (not shown). The movable cap 841 is a safety mechanism. The cap 841 may have a though hole for the NC (not shown) or may be punctured by the NC. Once the cap 841 is moved proximally into the tubular casing 840, an activation mechanism (not shown) can be triggered by moving the head 842. The force necessary for moving the head 842 may be referred to as injection force.
[0195] In the outer circumference of the tubular casing 840 two windows 843 are provided. The windows 843 are formed in protrusions 844 which extend outwardly from the outer circumference of the tubular casing 840. The protrusions 844 are positioned on diametrically opposite sides of the tubular casing 840.
[0196] In the state which is shown in FIG. 44a, the cap 841 is pushed into the tubular casing 840 and the protrusions 844 are received in the recesses 51713 which form the tapered portion 51714 of the lower part 5171 of the two-part RC 517. The cap 841 rests on the step 51712 and the upper end of the protrusion 844 rests against the bottom end of the upper part 5170 of the two-part RC 517. In this state the auto-injector syringe 84 thus has been brought into the condition, where the safety mechanism provided by the cap 841 has already been overcome and the actual force necessary for injection, in particular dispensing fluid from the barrel (not shown) of the syringe can be measured.
[0197] In FIG. 45a a schematic view of a fifth embodiment of the testing device 1 is shown. In FIG. 45a only the TC 7 and the AHEs 5 of the TD 1 are shown. This embodiment differs from the fourth embodiment by the layout of the RC 51. The RC 517 of the fifth embodiment differs from the RC 517 of the fourth embodiment in that the lower part 5171 is longer and does not have a tapered portion.
[0198] The embodiment of an auto-injector syringe 84 which is inserted into the two-part RC 517 in FIG. 45a is shown in FIG. 45b. As can be derived from FIG. 45b, the auto-injector syringe 84 only differs from the one shown in FIGS. 44b and 44c in that the cap 841 has a different shape and that no windows or protrusions are provided on the tubular casing 840 of the auto-injector syringe 84.
[0199] In the state as shown in FIG. 45a the cap 841 is pushed into the tubular casing 840. The cap 841 rests on the step 51712 and the upper end of the tubular casing 840 rests against the bottom end of the upper part 5170 of the two-part RC 517. In this state the auto-injector syringe 84 thus has been brought into the condition, where the safety mechanism provided by the cap 841 has already been overcome and the actual force necessary for injection, in particular dispensing fluid from the barrel (not shown) of the syringe can be measured.
[0200] In FIG. 46a a schematic sectional view of a sixth embodiment of the testing device 1 is shown. In FIG. 46a only the TC 7 and the AHEs 5 of the TD 1 are shown. This embodiment differs from the fourth and fifth embodiment by the layout of the RC 51. The two-part RC 517 of the sixth embodiment differs from the RC 517 of the fourth and fifth embodiment in that the upper part 5170 has a step 51702 formed in its lower section and that the lower part 5171 does not have a step but has a tapered section 51714 at the inner diameter of the tubular section 51711.
[0201] The embodiment of a passive safety guard syringe 85 which is inserted into the two-part RC 517 is shown schematically in FIG. 46b. In this embodiment, the passive safety guard syringe 85 comprises a syringe 8 with a plunger 81. At the proximal end of the plunger 81 a plunger head 853 is provided. Inside of the shield 851 a syringe body 850 is provided. The syringe body encloses at least part of the barrel 80 of the syringe 8 and is attached to the syringe 8. At the proximal end the shield 851 has a flange 852. At the proximal side of the flange 852 latch members 8510 extend in the proximal direction. At the distal end of the shield 851, a spring 854 is provided inside the shield 851. In the state as shown in FIG. 46b, the spring 854 is compressed by the syringe body 850 or the syringe 8. The NC of the syringe is covered by a SCS 83.
[0202] In order to introduce such a passive guard syringe 85 into the RC 51 the lower part 5171 can then be introduced into the IE, in particular the TC 7, from the bottom. The lower part 5171 can be attached to the TC 7 by screw-type connection. Subsequently, the passive guard syringe 85 may be inserted into the lower part 5171 of the two-part RC 517 from the top after the SCS 83 has been removed. Subsequently, the upper part 5170 can be inserted into the tempering chamber 70 of the TC 7 from the top until step 51702 rests against the top of the flange 852 of the shield 851. The latch members 851 are positioned in the inner diameter of the upper section of the upper part 5170. The latch members 851 can be biased outwardly by the plunger head 8530 once the plunger 853 is pushed in distal direction. Thereby, an unlocking mechanism (not shown) can be activated and the syringe body 850 with the syringe 8 can be released from the shield 851 and can be pushed in a proximal direction by the spring 854. In this retracted position, the NC is enclosed in the shield 851 and the position of the syringe 8 relative to the shield 851 is preferably locked by a locking mechanism (not shown).
[0203] Thereby, the moving force for moving the plunger 81 in the barrel 80 as well as the force for activating the unlocking mechanism can be measured with the TD 1 in the embodiment as shown in FIG. 46a.
[0204] It should be noted, that the invention can also be used for passive safety guard syringes having unlocking mechanisms and locking mechanisms which are different from the ones described above. Also auto-injector syringes having different activation mechanisms than the ones described above can be used.
[0205] As the TD 1 and method of the invention allow testing of the moving force for moving a plunger of a syringe in the syringe at different conditions of the syringe, the invention can be used to for example to identify a recommendable administration temperature for a PFS. The invention can also be used to formulate pharmaceuticals such that the moving force at room temperature is in a convenient range. Furthermore, the invention allows for determining an appropriate geometry of the syringe, for example an appropriate diameter of the barrel or NC. The invention can also be used to determine the injection force and/or unlocking force of passive safety guard syringes or auto-injector syringes at different temperatures.
[0206] The invention thus provides a novel approach to characterize the drug delivery system flow performance dependent on single component temperature dependent contribution.
[0207] PFS and other combination products are receiving increasing attention as the container closure system of choice for injectable drug products where self-administration is preferable. Subcutaneous injections typically require the development of high protein concentration formulations, which results in several challenges for manufacturing, stability, analytical, and delivery.
[0208] Viscosity depends on many factors, including protein concentration, molecule properties, formulation and product temperature, and impacts injection force and dosing accuracy. Injection force depends on viscosity and product properties but also device components and their variability, such as inner needle diameter, container diameter, container lubrication and temperature at actual product usage.
[0209] Several standards and guidance documents require testing device functionality, including studies at upper and lower end temperatures. For example ISO 11608-1 delineates preconditioning temperatures for needle-based injection systems, the FDA guidance “technical considerations for pen, Jet, and related Injectors . . . ” requires the verification that injector performance is not adversely affected by environmental conditions such as “extreme conditions of use testing”.
[0210] It was poorly researched how and which component of the device contributes to an injection force change when modulating the device temperature (e.g. needle temperature vs. formulation temperature vs. lubrication temperature)
[0211] The invention provides a proprietary technology to selectively control and study the temperature of the syringe needle and the syringe barrel during injection force measurements to characterize the impact on injection force.
[0212] For example, 1 mL and 2 mL syringes with 25G, 27G and 29G needles and 2 different protein formulations can be tested at 2-8° C., 25° C. and 60° C. It has been identified that moving force, which corresponds to the injection force, and the device performance was significantly dependent on temperature, and that specific device components had different impact on the results.
LIST OF REFERENCE NUMERALS
[0213] 1 Testing device
[0214] 10 Intermediate element
[0215] 2 Load frame
[0216] 20 base
[0217] 21 post
[0218] 22 connecting disk
[0219] 3 Fixture
[0220] 30 Support frame
[0221] 300 Support plate
[0222] 3000 aperture
[0223] 3001 inner thread
[0224] 3002 connecting hole
[0225] 301 Poles
[0226] 3010 Insulation ring
[0227] 302 Carrier Plate
[0228] 3020 Tray
[0229] 303 Foot
[0230] 5 Annular holding element
[0231] 50 Flange holder
[0232] 500 body
[0233] 501 head
[0234] 502 through hole
[0235] 503 outer thread
[0236] 504 collar
[0237] 51 Receiving cylinder
[0238] 510 body
[0239] 511 head
[0240] 512 through hole
[0241] 513 outer thread
[0242] 514 measuring hole
[0243] 515 inner thread
[0244] 516 step
[0245] 517 two-part RC
[0246] 5170 upper part
[0247] 51700 ring section
[0248] 51701 tubular section
[0249] 51702 step
[0250] 5171 lower part
[0251] 51710 ring section
[0252] 51711 tubular section
[0253] 51712 step
[0254] 51713 recess
[0255] 51714 tapered section
[0256] 52 Needle holder
[0257] 520 Disc body
[0258] 5200 body
[0259] 5201 head
[0260] 5202 through hole
[0261] 5203 outer thread
[0262] 5204 measuring hole
[0263] 521 Threaded bush
[0264] 5210 body
[0265] 5211 head
[0266] 5212 through hole
[0267] 5213 outer thread
[0268] 5214 insert
[0269] 5215 recess
[0270] 6 Spacer
[0271] 60 wall
[0272] 61 receiving recess
[0273] 62 inner thread
[0274] 63 Tube
[0275] 64 inlet
[0276] 65 outlet
[0277] 7 Tempering cylinder
[0278] 70 Wall
[0279] 71 Connector
[0280] 700 tempering room
[0281] 701 inner thread
[0282] 8 Syringe
[0283] 80 barrel
[0284] 800 lumen
[0285] 801 flange
[0286] 802 lumen
[0287] 803 shoulder
[0288] 804 neck
[0289] 81 plunger
[0290] 810 rod
[0291] 811 stopper
[0292] 82 dispensing opening
[0293] 820 needle cannula
[0294] 821 Luer cone
[0295] 83 Syringe closing system
[0296] 84 auto-injector syringe
[0297] 840 tubular casing
[0298] 841 cap
[0299] 842 head
[0300] 843 window
[0301] 85 passive safety guard syringe
[0302] 850 syringe body
[0303] 851 shield
[0304] 8510 latch member
[0305] 852 flange
[0306] 853 plunger head
[0307] 854 spring
[0308] 9 Sensing unit
[0309] 90 Sensor
[0310] 91 Sensor
[0311] 92 Sensor
