SEPARATING LAYER FOR THE TRANSPORT OF PHARMACEUTICAL SECONDARY PACKAGINGS

Abstract

A separating layer for the transport of pharmaceutical secondary packagings and to a transport system for transporting pharmaceutical secondary packagings which comprises the separating layer are provided. The separating layer is a polymer layer having a planar section extending in an axial direction along a longitudinal axis and an elevation extending normal to the longitudinal axis. The separating layer has in the axial direction a normal spring force that is 0.2 to 5 N.

Claims

1. A transport system for transporting pharmaceutical secondary packagings, comprising: a transport box; and two pharmaceutical secondary packagings in the transport box, wherein the two pharmaceutical secondary packagings comprise each 10 to 200 pharmaceutical primary packagings, wherein, after running a transport simulation program according to ASTM D4169-16, DC12, not including program I, safety level I, there is a condition selected from a group consisting of: 20.0 or less particles per cm.sup.2 having a size of 2 μm to 25 μm on an outside and/or an inside of each of the pharmaceutical primary packagings; 6.0 or less particles per cm.sup.2 having a size of 5 μm to 25 μm on the outside and/or the outside of each of the pharmaceutical primary packagings; 2.0 or less particles per cm.sup.2 having a size of 10 μm to 25 μm on the outside and/or the inside of each of the pharmaceutical primary packagings; less than 0.1 particles per cm.sup.2 having a size of 25 μm or more on the outside and/or the inside of each of the pharmaceutical primary packagings; and any combinations thereof.

2. The transport system of claim 1, wherein the transport system comprises a separating layer comprising a planar section, and wherein the separating layer is between the two pharmaceutical secondary packagings in the transport box.

3. The transport system of claim 2, wherein the separating layer comprises a polymer layer having a planar section extending in an axial direction along a longitudinal axis and an elevation extending normal to the longitudinal axis, the separating layer having a normal spring force that is 0.2 to 5 N.

4. The transport system of claim 3, wherein the separating layer further comprises a second planar section, wherein the elevation is arranged between the planar section and the second planar section.

5. The transport system of claim 4, wherein the separating layer is arranged such that the planar section and the second planar section are in contact with bottom faces of the two pharmaceutical secondary packagings, respectively, with the elevation projecting between the two pharmaceutical secondary packagings so that the two pharmaceutical secondary packagings are not in contact with one another.

6. The transport system of claim 3, wherein the planar section contacts a bottom face of a first of the two pharmaceutical secondary packagings and contacts a top face of a second of the two pharmaceutical secondary packagings.

7. The transport system of claim 3, wherein the normal spring force is 0.5 to 2 N.

8. The transport system of claim 3, wherein the separating layer has an axial spring force that is 1 to 50 N.

9. The transport system of claim 8, wherein the axial spring force is 20 to 30 N.

10. The transport system of claim 1, wherein the two pharmaceutical secondary packagings are trough-shaped with an edge along a top face which extends along a plane of the top face.

11. The transport system of claim 1, wherein the two pharmaceutical secondary packagings have a sterile interior.

12. The transport system of claim 3, wherein the transport box is made of the polymer of the separating layer.

13. The transport system of claim 3, wherein the separating layer has a width and the transport box has an internal width and the transport system further comprises a ratio of the width to the internal width of 0.8 to 1.5.

14. The transport system of claim 13, wherein the separating layer has a length and the transport box has an internal length and the transport system further comprises a ratio of the length to the internal length of 1.1 to 2.0.

15. The transport system of claim 3, wherein the separating layer has a length and the transport box has an internal length and the transport system further comprises a ratio of the length to the internal length of 1.1 to 2.0.

16. The transport system of claim 1, wherein the transport system, in an impact test according to the Incline Impact Test ASTM D880-92 (2015) with an impact speed of 2.14 m/s, exhibits damage to not more than 50% of the pharmaceutical primary packagings.

17. The transport system of claim 1, wherein, after running a transport simulation program according to ASTM D4169-16, DC12, not including program I, safety level I, there are a condition selected from a group consisting of: 40.0 or less particles per cm.sup.2 having a size of 2 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 16.0 or less particles per cm.sup.2 having a size of 5 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 3.5 or less particles per cm.sup.2 having a size of 10 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 0.9 or less particles per cm.sup.2 having a size of 15 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 0.0 particles per cm.sup.2 having a size of 25 μm or more on each individual internal wall of the pharmaceutical secondary packaging; and any combinations thereof.

18. The transport system of claim 1, wherein, after running a transport simulation program according to ASTM D4169-16, DC12, not including program I, safety level I, there are 6000 or less particles having a size of 15 μm to 25 μm on an outside or an inside of each individual pharmaceutical primary packaging.

19. The transport system of claim 1, wherein, after running a transport simulation program according to ASTM D4169-16, DC12, not including program I, safety level I, there are 50000 or less particles having a size of 2 μm to 25 μm on an outside or an inside of each individual pharmaceutical primary packaging.

20. A transport system for transporting pharmaceutical secondary packagings, comprising: a transport box; and two pharmaceutical secondary packagings in the transport box, wherein the two pharmaceutical secondary packagings comprise each 10 to 200 pharmaceutical primary packagings, wherein, after running a transport simulation program according to ASTM D4169-16, DC12, not including program I, safety level I, there is a condition selected from a group consisting of: 40.0 or less particles per cm.sup.2 having a size of 2 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 16.0 or less particles per cm.sup.2 having a size of 5 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 3.5 or less particles per cm.sup.2 having a size of 10 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 0.9 or less particles per cm.sup.2 having a size of 15 μm to 25 μm on each individual internal wall of the pharmaceutical secondary packaging; 0.0 particles per cm.sup.2 having a size of 25 μm or more on each individual internal wall of the pharmaceutical secondary packaging; and any combinations thereof.

21. A transport system for transporting pharmaceutical secondary packagings, comprising: a transport box; and two pharmaceutical secondary packagings in the transport box, wherein the two pharmaceutical secondary packagings comprise each 10 to 200 pharmaceutical primary packagings, wherein, after running a transport simulation program according to ASTM D4169-16, DC12, not including program I, safety level I, there are 6000 or less particles having a size of 15 μm to 25 μm on an outside or an inside of each individual pharmaceutical primary packaging.

Description

BREIF DESCRIPTION OF THE DRAWINGS

[0043] FIG. 1 shows a packaging system comprising tub, nest, syringes, cover sheet and protective film;

[0044] FIG. 2 is a plan view of a separating layer according to one embodiment of the invention;

[0045] FIG. 3 is a cross section of a separating layer according to one embodiment of the invention;

[0046] FIG. 4 is a cross section of a transport system according to one embodiment of the invention;

[0047] FIG. 5 shows a particle count per cm.sup.2 on the external wall of the carpules; and

[0048] FIG. 6 shows a particle count per cm.sup.2 on the internal wall of the tub.

DETAILED DESCRIPTION

[0049] FIG. 1 shows an exploded view of a packaging system (1) used for transporting syringes (5). The packaging system (1) comprises a protective film (2), a cover sheet (3), a nest (4), syringes ((5), pharmaceutical primary packaging) and a tub ((6), pharmaceutical secondary packaging). The shape of the packaging system (1) is defined by the tub (6). The syringes (5) are held by the nest (4). The nest (4) is in turn inserted in the tub (6). The syringes (5) are not in direct contact with the tub (6). The syringes (5) are covered by the cover sheet (3) and the tub (6) is sealed with the protective film (2). The sealed tub (6) may additionally be enclosed with one or more bags (12).

[0050] FIG. 2 shows a plan view of a separating layer (7) according to one embodiment of the invention and FIG. 3 shows a cross section of a separating layer (7) according to one embodiment of the invention. As can be seen in FIGS. 2 and 3 the separating layer (7) is formed from one piece. The separating layer (7) consists of planar sections (8) and from the sections for forming the elevation (9) the elevations (10) are formed by folding the separating layer (7).

[0051] FIG. 4 shows the cross section of a transport system according to one embodiment of the invention. The transport box (11) contains four rows on top of one another, each comprising three packaging systems (1) side by side. The packaging systems (1) within a row and the respective rows are each separated by a separating layer (7). The packaging systems (1) within a row are not in contact with one another. In the case of a lateral impact the force is cushioned by the elevations (10) of the separating layers (7). It can be seen that in a preferred transport orientation the open side of the tubs points downwards and the elevations are likewise oriented downwards (see FIG. 4).

METHODS OF MEASUREMENT

[0052] The axial spring force in the longitudinal direction is measured as follows.

[0053] A separating layer has a piece comprising an elevation and two planar sections each having a length of 60 mm, i.e. from the respective outer fold seam to the end of the piece, cut out of it. The sample is clamped into a universal testing machine (Test GmbH, model 106.2 kN) such that the clamping grips are each located centrally in the planar sections and spaced 20 mm apart from the elevation, i.e. from the respective outer fold seam. The clamping grips are then oriented so as to be spaced apart such that a gap of at least 3 cm is formed between the two planar sections, i.e. a spacing between the clamping grips of 14 cm is established. The clamping grips are screwed tight to just hold the material securely. Measurement is carried out in the vertical direction. During the actual measurement the upper clamping grip is moved downwards at a constant speed of 500 mm/min and the force required therefor is continuously measured. As soon as the two planar sections touch the measurement is terminated. This is indicated by the force increasing rapidly and finally exceeding a value of 25 N (=end point). The axial spring force in the longitudinal direction is the force measured at a gap of 26.5 mm between the two planar sections, i.e. the force measured 26.5 mm before the clamping grips have been moved together close enough for the value to exceed 25 N. The measurement is repeated 10 times with a new separating layer and an average is formed.

[0054] The normal spring force in the longitudinal direction is measured as follows.

[0055] In a transport system, for example a transport box made of Akylux®, a lowermost layer of pharmaceutical secondary packagings, for example adaptiQ®, syriQ® or cartriQ™ from SCHOTT AG, is inserted. Atop this lowermost layer comprising secondary packagings the separating layer is inserted, which is configured such that there is an elevation between each of the pharmaceutical secondary packagings, and optionally between the pharmaceutical secondary packagings and the wall of the transport box, and the planar sections are located above the pharmaceutical secondary packagings. The elevations project downwards into the gaps between the pharmaceutical secondary packagings. Since the separating layer folded immediately before the test is longer than the length of the transport box and/or since the folded or bent elevations project into the interspaces, the separating layer is tensioned. The force necessary to prevent the separating layer from relaxing from the tensioned state for 10 seconds, i.e. from curving upwards, is measured. To this end a weight is placed in the middle of the middle planar section (for an uneven number of planar sections) or in the middle of one of the middle sections (for an even number of planar sections) and pressed downwards. The position of the separating layer is marked on the wall of the transport box with a thin pencil. The weight is then released and the time is simultaneously stopped. After 10 seconds it is checked whether the separating layer bearing the weight has relaxed over the marking, i.e. has curved over the marking. The test is repeated with varying weights and the weight that is just sufficient for the separating layer not to rise above the marking within 10 seconds is determined (=normal spring force in longitudinal direction).

[0056] The transport simulation program that was run is ASTM D4169-16, DC12 (not including program I), safety level I.

[0057] The particle contamination on the outside of the primary packaging is measured as follows.

[0058] The primary packaging is removed from the secondary packaging under laminar flow. The pharmaceutical primary packagings are then sealed so that no test liquid can penetrate into the primary packaging. 10 carpules sealed at both ends with a stopper and having an outer surface area of 15.76 cm.sup.2 (used for example 3), of sealed pharmaceutical primary packagings is placed in a beaker in 100 mL of test liquid. To detach the particles from the surface the solution is stirred at 300 to 350 rpm for 20 seconds using a magnetic stirrer. After 15 minutes, 5 ml of the solution are analysed with a liquid particle counter (Pacific Scientific HIAC Royco, Model 9703) and the particle contamination is determined against a background measurement of the test liquid. This method and instrument allow reliable determination of particles with a size of 0.5 μm or larger. Analysis of the test liquid present is carried out 5 times in total. The average of the obtained values and the external surface area and the number of pharmaceutical primary packagings is then used to calculate the number of particles per square centimetre (particle count/cm.sup.2) on the external surface.

[0059] The particle contamination on the inside of the tub is measured as follows.

[0060] The protective film, protective layer and the nest comprising the pharmaceutical primary packagings are removed from the tub under laminar flow. The tub is then washed out on all sides with 100 mL of test liquid, swirled several times and subsequently transferred into a beaker. After 15 minutes, 5 ml of the solution are analysed with a liquid particle counter (Pacific Scientific HIAC Royco, Model 9703) and the particle contamination is determined against a background measurement of the test liquid. This method and instrument allow reliable determination of particles with a size of 0.5 μm or larger. Analysis of the test liquid present is carried out 5 times in total. The particle count was calculated based on the area of the inside (=internal wall) of the tub and the measured values.

[0061] The particle contamination on the inside of a pharmaceutical primary packaging is measured as follows.

[0062] The protective film, protective layer and the nest comprising the pharmaceutical primary packagings are removed from the tub under laminar flow. The inside of a pharmaceutical primary packaging is then rinsed out on all sides with test liquid by filling the pharmaceutical primary packaging with the fill amount of test liquid nominal for the pharmaceutical primary packaging, swirled several times and subsequently transferred into a beaker. If a pharmaceutical primary packaging has more than one opening this may be sealed with a particle-free film. After 15 minutes, 5 mL of the solution is analysed with a liquid particle counter (Pacific Scientific HIAC Royco, Model 9703) and the particle contamination is determined against a background measurement of the test liquid. If the primary packaging has a nominal volume smaller than the required amount for the test, the test liquids from a multiplicity of primary packagings from the same secondary packaging are combined as a pool. This method and instrument allow reliable determination of particles with a size of 0.5 μm or larger. Analysis of the test liquid present is carried out 5 times in total. The particle count was calculated based on the area of the inside (=internal wall) of the pharmaceutical primary packaging and the measured values.

[0063] The impact test employed herein is the “Incline Impact Test ASTM D880-92 (2015)” but at 1.2× loading, i.e. the impact speed is 2.14 m/s instead of 1.75 m/s as per the standard. Counted as damage is a fracture, kink and/or crack in the primary and/or secondary pharmaceutical packaging.

[0064] A kink is apparent when the test specimen is deformed and can no longer be returned to its starting shape, i.e. a kink, more particularly crazing, is visible. A crack is characterized by a localized separation of the material of small width but considerable length and depth. A fracture is a destruction of the molecular bond and thus the test specimen has a free surface (fracture surface).

EXAMPLES 1 and 2

[0065] A separating layer made of polypropylene (Akylux®) having a length of 108 cm and a width of 22 cm was folded to obtain 4 triangular elevations and 3 planar sections, wherein a side length of an elevation was 5.3 cm long and the planar sections were each 22 cm long. The thickness of the separating layer was 2.0 to 3.5 mm. The transport box (=transport system) had a length, width and height of 77*23*50.8 cm and was likewise made of polypropylene (Akylux®). The pharmaceutical primary packagings and secondary packagings employed were commercially available tubs (cartriQ™ from Schott AG) that had been welded into a film.

[0066] The normal spring force and the axial spring force were determined as described hereinabove:

TABLE-US-00001 Example Thickness Normal spring force Axial spring force # [mm] [N] [N] 1 2.0 0.6 6.4 2 3.5 2.1 28.0

EXAMPLES 3 AND 4

[0067] Two transport boxes were provided; one having a planar separating layer without elevations (example 3) and one having a separating layer according to an embodiment of the invention (example 4). To this end two transport boxes (=transport system) having a length, width and height of 770*230*508 mm and made of polypropylene (Akylux®) each had a row of three commercially available tubs (cartriQ™ from Schott AG) that had been welded into a film placed inside them with the opening facing down. One transport box then had a planar Akylux® polymer insert, having dimensions of 758*220*3.5 mm and lacking elevations, placed inside it while the other transport box had a separating layer made of polypropylene (Akylux®), having a length of 108 cm and a width of 22 cm and folded in such a way that 4 triangular elevations and 3 planar sections resulted, placed inside it, wherein a side length of an elevation was 5.3 cm long and the planar sections were each 22 cm long. The thickness of the separating layer was 2.0 mm. Another layer of tubs and another layer of the respective separating layer were then placed in the box and the procedure was repeated until the box was full. Next, the transport simulation program ASTM D4169-16, DC12 (not including program I), safety level I was run and subsequently the particle count and the size on the external surface of the carpules (=pharmaceutical primary packagings) and the internal wall of the tub (=pharmaceutical secondary packagings) were determined as described hereinabove. The results are shown in FIG. 5 (particle count on the external wall of the pharmaceutical primary packagings) and FIG. 6 (particle count on the internal wall of the pharmaceutical secondary packagings), wherein the black bars represent the respective particle counts of example 3 and example 4 is represented by chequered bars.

TABLE-US-00002 Particle count per cm.sup.2 on external wall of carpules Example # ≥2 μm ≥5 μm ≥10 μm ≥25 μm 3 21.0 6.1 2.1 0.1 4 10.6 2.7 0.7 0.0 Particle count per cm.sup.2 on internal wall of the tub Example # ≥2 μm ≥5 μm ≥10 μm ≥15 μm ≥25 μm 3 41.0 16.5 3.6 1.0 0.0 4 33.6 13.9 3.1 0.9 0.0

[0068] It is apparent from the table and FIGS. 5 and 6 that through the use of a separating layer according to one embodiment of the invention the particle count on the external surface of the pharmaceutical primary packagings (=carpules) was reduced by more than half in all size ranges compared to a completely planar separating layer. The particle count on the internal wall of the pharmaceutical secondary packagings (=tubs) was likewise markedly reduced in all size ranges using a separating layer according to one embodiment of the invention compared to a completely planar separating layer. Both in example 3 and in example 4 particles larger than 25 μm were barely detectable (particle count <0.1).

[0069] In addition, transport boxes were packed as described hereinabove in examples 3 and 4 and impact tests as described hereinabove were performed. While 66% of the outermost pharmaceutical secondary packagings (=tubs) facing the side of impact were damaged in the transport box with the planar separating layers (example 3), only 2% of the outermost pharmaceutical secondary packagings (=tubs) facing the side of impact were damaged when using separating layers according to an embodiment of the invention.

LIST OF REFERENCE NUMERALS

[0070] 1 Packaging system

[0071] 2 Protective film

[0072] 3 Protective layer

[0073] 4 Nest

[0074] 5 Syringe (pharmaceutical primary packaging)

[0075] 6 Tub (pharmaceutical secondary packaging)

[0076] 7 Separating layer

[0077] 8 Planar section

[0078] 9 Section for forming the elevation

[0079] 10 Elevation

[0080] 11 Transport box

[0081] 12 One or more bags