Supporting structure for concurrently supporting a plurality of vials, use thereof and process for the treatment of such vials

Abstract

A supporting structure for concurrently supporting a plurality of vials is provided. The supporting structure includes a carrier having apertures or receptacles, into which the vials can be inserted to be supported therein on the carrier. The vials have a bottom that forms a base, a cylindrical side wall, and an annular transition region between the base and the cylindrical side wall. The carrier has a retaining protrusion at a lower end of the aperture or receptacle that extends into the respective aperture or receptacle inward in radial direction. The retaining protrusion supports the vial in cooperation with the transition region outside the base in such a manner that the bottoms or bases of the vials jut out of the apertures or receptacles of the carrier and are freely accessible from the lower side of the carrier.

Claims

1. A supporting structure, comprising: a plurality of vials, wherein each of the plurality of vials has a horizontal base, a cylindrical side wall, and an annular transition region between the horizontal base and the cylindrical side wall; a carrier having an upper side, a lower side opposite the upper side and a plurality of receptacles into which the plurality of vials are at least partially inserted; and a retaining protrusion in each of the plurality of receptacles that protrudes into the receptacle in an inward radial direction at a lower end of the respective receptacle, wherein the retaining protrusion contacts or supports an associated vial of the plurality of vials at the transition region of the horizontal base so that the horizontal base of each vial juts out of the respective receptacle of the carrier and is accessible from the lower side of the carrier.

2. The supporting structure as claimed in claim 1, wherein the retaining protrusion has a shape that is matched to a shape and dimension of the transition region of the associated vial so that the transition region is supported by a positive-fit engagement.

3. The supporting structure as claimed in claim 1, wherein each of the plurality of vials comprise a neck portion, and wherein the carrier is configured so that the vials are not supported at the neck portion.

4. The supporting structure as claimed in claim 1, wherein the transition region of each of the plurality of vials has a radius of curvature, and wherein the retaining protrusion has a surface facing a respective transition region that is inclined toward the lower side of the carrier or is curved.

5. The supporting structure as claimed in claim 4, wherein the surface of the retaining protrusion facing the respective transition region is inclined toward the lower side of the carrier at an angle relative to a vertical axis perpendicular to a plane spanned by the carrier.

6. The supporting structure as claimed in claim 5, wherein the angle is in a range between 10 and 70 degrees.

7. The supporting structure as claimed in claim 5, wherein the angle corresponds to an angle of a tangent to the transition region.

8. The supporting structure as claimed in claim 4, wherein the surface of the retaining protrusion facing the respective transition region has a concave curve.

9. The supporting structure as claimed in claim 4, wherein the retaining protrusion has a front end with a straight portion, the straight portion extending perpendicular to a plane spanned by the carrier.

10. The supporting structure as claimed in claim 9, wherein the straight portion has an axial length in a direction perpendicular to the plane spanned by the carrier that is in a range of 0.1 to 5.0 mm.

11. The supporting structure as claimed in claim 4, wherein the radius of curvature is in a range of 1.0 to 10.0 mm, and wherein the retaining protrusion is matched to a shape of the transition region of the associated vial so that the bas of the vial juts out of the receptacles of the carrier by a distance in a range between 0.01 and 5.0 mm.

12. The supporting structure as claimed in claim 1, wherein the retaining protrusion is circumferential.

13. The supporting structure as claimed in claim 1, wherein the retaining protrusion is two retaining protrusions that are formed at the lower end of a respective receptacle at equiangular intervals, wherein the two retaining protrusions are spaced apart by gaps of a circumferential length that is smaller than a circumferential length of the two retaining protrusions.

14. The supporting structure as claimed in claim 1, wherein the receptacles are formed so that an upper end of the associated vial does not protrude beyond the upper side of the carrier.

15. The supporting structure as claimed in claim 14, wherein the receptacle is formed by a circumferential side wall and the retaining protrusion is formed integrally with the circumferential side wall at a lower end thereof.

16. The supporting structure as claimed in claim 15, further comprising: slots formed at the lower end and on opposite sides of the circumferential side wall.

17. The supporting structure as claimed in claim 1, wherein the carrier is formed as a supporting plate, in which the apertures are formed, wherein the retaining protrusions are formed integrally with the supporting plate at lower ends of the apertures.

18. The supporting structure as claimed in claim 17, wherein guiding members are provided at least in sections on the upper side of the supporting plate along edges of the apertures, which extend perpendicular to the upper side of the supporting plate for preventing a collision of vials supported in directly adjacent apertures.

19. The supporting structure as claimed in claim 1, wherein the receptacle is matched to an outer diameter of the associated vial supported therein so that radial play exists above the transition regions.

20. The supporting structure as claimed in claim 1, wherein the retaining protrusion has a vertical straight portion at an end thereof where the retaining protrusion contacts the transition region.

21. The supporting structure as claimed in claim 1, wherein the retaining protrusion contacts the transition region so that the associated vial is centered within the receptacle.

22. The supporting structure as claimed in claim 1, wherein the plurality of vials do not project above the upper side of the carrier.

23. A supporting structure comprising: a vial, wherein the vial has a horizontal base, a cylindrical side wall, and an annular transition region between the horizontal base, and the cylindrical side wall, and an annular transition region between the horizontal base and the cylindrical side wall; a carrier having an upper side, a lower side that is opposite to the upper side, and a plurality of receptacles into which the vial van be at least partially inserted so that the vial is supported at the carrier; and a plurality of retaining protrusions, one each in each of the plurality of receptables, wherein each of the plurality of retaining protrusions protrudes inwardly in a radial direction into an associated receptacle at a lower end of the associated receptacle, so that the vial, when in the receptable, is supported at the transition region, and so that the horizontal base of the vial juts out of the associated receptacle and is accessible from the lower side of supporting structure.

24. A transport or packaging container, comprising: a box-shaped transport or packaging container; and a supporting structure accommodated in the box-shaped transport or packaging container for supporting the plurality of vials inside the transport or packaging container, the supporting structure comprising: a plurality of vials, wherein each of the plurality of vials has a horizontal base, a cylindrical side wall, and an annular transition region between the horizontal base and the cylindrical side wall; a carrier having an upper side, a lower side opposite the upper side and a plurality of receptacles into which the plurality of vials are at least partially inserted; a retaining protrusion that protrudes into a respective receptacle of the plurality of receptacles in an inward radial direction at a lower end of the respective receptacle; wherein the retaining protrusion contacts or supports an associated vial of the plurality of vials at the transition region of the horizontal base so that the horizontal bases of the plurality of vial juts out of the respective receptacle of the carrier and is accessible from the lower side of the carrier.

25. The transport or packaging container as claimed in claim 24, wherein the plurality of vials are supported on the supporting structure.

26. A method of concurrently supporting a plurality of vials using a supporting structure, comprising: selecting a supporting structure that comprises a carrier having an upper side, a lower side opposite to the upper side, and a plurality of apertures or receptacles, the carrier having a retaining protrusion that protrudes into a respective aperture or receptacle at the lower end of a respective aperture or receptacle inward in radial direction; selecting vials that have a bottom, which forms a horizontal base, a cylindrical side wall, and an annular transition region between the horizontal base and the cylindrical side wall; and inserting the vials, at least partially, into the apertures or receptacles so that the retaining protrusion contacts the transition region of the respectively associated vial, so that the transition regions of the vials are supported outside the horizontal bases in such a manner that the bottoms or horizontal bases of the vials jut out of the apertures or receptacles of the carrier and are freely accessible from the lower side of the carrier.

27. A method for the treatment of vials, comprising: providing a supporting structure having an upper side, a lower side opposite to the upper side, and a plurality of apertures or receptacles, the supporting structure having a retaining protrusion that protrudes into the respective aperture or receptacle at a lower end of a respective aperture or receptacle inward in radial direction; providing a plurality of vials, wherein the vials have a bottom, which forms a horizontal base, a cylindrical side wall, and an annular transition region between the horizontal base and the cylindrical side wall; disposing the vials in the apertures or receptacles of the supporting structure so that the retaining protrusion contacts a vial at the transition region outside the horizontal bases in such a manner that the bottoms or horizontal bases of the vials jut out of the apertures or receptacles of the carrier and are freely accessible from the lower side of the carrier; and treating the vials while being supported at the supporting structure and while being accommodated in the apertures or receptacles.

28. The method as claimed in claim 27, wherein the treating step is a process selected from the group consisting of freeze-drying or lyophilization of a substance inside the vials; axially displacing the vials in the apertures or receptacles by fluid flow acting on the vials; cleaning of outer surfaces of the vials by fluid flowing into the apertures or receptacles; drying the outer surfaces of the vials by a gas flow flowing into the apertures or receptacles of the supporting structure; and any combinations thereof.

29. The method as claimed in claim 27, wherein the treating step comprises freeze-drying or lyophilization of a substance for pharmaceutical or medical applications inside the vials, wherein the freeze-drying or lyophilization comprises: disposing the supporting structure together with the vials supported by it on a cooling surface so that the bottoms or horizontal bases of the vials rest directly on the cooling surface; and lyophilizing the substance for pharmaceutical or medical applications inside the vials, wherein the vials continue to be accommodated in the apertures or receptacles during lyophilization while the bottoms or horizontal bases of the vials rest directly on the cooling surface.

30. The method as claimed in claim 29, wherein the apertures or receptacles of the supporting structure are formed by circumferential side walls, wherein the vials are completely accommodated in the apertures or receptacles, wherein interspaces are formed between the side walls of directly adjacent apertures or receptacles of the supporting structure into which cooling fingers protrude which surround the apertures or receptacles of the supporting structure at least in sections.

31. The method as claimed in claim 29, wherein the carrier is formed as a supporting plate, in which the apertures or receptacles are formed, wherein the retaining protrusions are formed integrally with the supporting plate at lower ends of the apertures or receptacles, wherein the lower side of the supporting plate rests directly on the cooling surface.

32. The method as claimed in claim 29, wherein: the bottoms of the vials are flat and the bottoms are in full surface contact with the cooling surface during lyophilization; or the bottoms of the vials are concavely curved or flat and a gap is formed between the cooling surface and the associated bottoms of the vials during lyophilization; or the bottoms of the vials are concavely curved and respectively rest on convex projections on the cooling surface.

33. The method as claimed in claim 27, wherein the treating step comprises axially displacing the vials in the apertures or receptacles by the action of fluid flow, wherein the axially displacing comprises: ejecting fluid from nozzles or tubes disposed below the vials and centered with the respective aperture or receptacle in a direction perpendicular to a plane spanned by the carrier so that the fluid acts on the bottoms or horizontal bases of the vials to lift the vials inside the apertures or receptacles by a distance smaller than an axial length of the vials.

34. The method as claimed in claim 27, wherein the treating step comprises axially displacing the vial in the apertures or receptacles by the action of fluid flow, wherein the axially displacing comprises discharging fluid from nozzles or tubes that are disposed above the vials and centered with the respective aperture or receptacle in a direction perpendicular to a plane spanned by the carrier so that the fluid acts on upper ends of vials to push the vials down inside the apertures or receptacles to push the vials out of the apertures or receptacles.

35. The method as claimed in claim 27, wherein the treating step comprises cleaning the outer surfaces of the vials by fluid flow, wherein the cleaning step further comprises spraying fluid by a spraying device that is below and/or above the apertures or receptacles and in alignment with the apertures or receptacles so that outer surfaces of the vials are cleaned by the fluid.

36. The method as claimed in claim 35, wherein the fluid is sprayed as a liquid or liquid mist from the lower side into the apertures or receptacles, wherein the vials are lifted inside the apertures or receptacles by the spraying of the liquid and are temporarily not supported on the retaining protrusions.

37. The method as claimed in claim 27, wherein the treating step comprises the step of drying the outer surfaces of the vials further comprises: spraying gas into the apertures or receptacles at least from the lower side of the supporting structure for drying outer surfaces of the vials, wherein the vials are lifted in the apertures or receptacles by the spraying of the gas and are temporarily not supported on the retaining protrusions.

38. The method as claimed in claim 27, wherein the step of disposing the vials in the apertures or receptacles comprises one of: inserting the vials into the apertures or receptacles vertically from the upper side of the carrier; inserting the vials into the apertures or receptacles vertically from the lower side of the carrier under elastic deformation of the retaining protrusions; inserting the vials into the apertures or receptacles vertically from the lower side of the carrier under elastic deformation of side walls of the apertures or receptacles; and inserting the vials into the apertures or receptacles vertically from the lower side of the carrier under elastic deformation of the retaining protrusions and of side walls of the apertures or receptacles.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Hereinafter, the invention will be described by way of example and with reference to the accompanying drawings, from which further features, advantages and problems to be solved may become apparent. In the drawings:

(2) FIGS. 1a and 1b show the typical geometry of vials as a preferred example of a pharmaceutical container, which is used for a supporting structure or a method according to the present invention;

(3) FIGS. 2a-2d show the supporting of a lower edge portion of a vial on retaining protrusions of a supporting structure according to the present invention;

(4) FIGS. 3a-3b are two examples of a supporting structure according to the present invention in a plan view;

(5) FIGS. 3c-3e show three examples of the shape of retaining protrusions of a supporting structure according to the present invention in a plan view;

(6) FIG. 4a shows a supporting structure according to a first embodiment of the present invention in a side view;

(7) FIG. 4b shows the supporting structure of FIG. 4a, which is accommodated in a transport and packaging container;

(8) FIG. 5 shows a supporting structure according to a second embodiment of the present invention in a perspective top view;

(9) FIGS. 6a-6d are examples for the use of a supporting structure according to the present invention in freeze-drying, in each case in a schematic side view;

(10) FIG. 7a shows an example for the use of a supporting structure according to the present invention for a cleaning of the inner surfaces of the vials;

(11) FIG. 7b shows an example of the use of a supporting structure according to the present invention for a cleaning of the outer surfaces of the vials;

(12) FIG. 7c shows an example of the use of a supporting structure according to the present invention during lifting and lowering the vials in receptacles of the supporting structure and during the drying of the outer surfaces of the vials;

(13) FIG. 7d is an example of the use of a supporting structure according to the present invention for cleaning of the outer sides of the vials, which is sealed by means of a press-fit closure cap;

(14) FIG. 7e is an example of the use of a supporting structure according to the present invention during lifting and lowering the vials in receptacles of the supporting structure and the drying of the outer surfaces of the vials, which are sealed by means of a press-fit closure cap;

(15) FIG. 8 is another example of the use of a supporting structure according to the present invention for the removal of the vials out of receptacles of the supporting structure via the lower ends of the receptacles; and

(16) FIG. 9 is a schematic flow diagram of a method according to the present invention for the treatment of vials for substances for pharmaceutical or medical applications.

(17) Throughout the drawings, identical reference numerals designate identical or substantially equivalent elements or groups of elements.

DETAILED DESCRIPTION

(18) FIG. 1a shows the geometry of typical 2R-Vials to 50R-Vials (with a capacity of 4 ml to 62 ml), which is summarized in Table 1 below.

(19) TABLE-US-00001 TABLE 1 typical geometry of 2R-vials to 50R-vials d3 h2 s2 t volume toler- a d1 toler- d2 mm d4 h1 toler- mm h3 r1 r2 s1 toler- mm mm Type [ml] ance [mm] mm ance mm max. mm mm ance min. mm tolerance mm mm mm ance min. max. 2R 4 0.5 1 16 0.15 13 10.5 7 35 0.5 22 8 0.5 2.5 1.5 1 0.04 0.6 0.7 4R 6 45 32 6R 10 1.2 22 0.2 20 16.5 12.6 40 26 8.5 3.5 2 0.7 8R 11.5 45 31 10R 13.5 1 24 45 30 9 4 15R 19 60 45 20R 26 1.5 1.5 30 0.25 17.5 55 0.7 35 10 0.75 5.5 2.5 1.2 0.05 1 25R 32.5 65 45 30R 37.5 75 55 50R 62 4 2.5 40 0.44 73 0.75 49 6 4 1.5 0.07 0.9 1.5

(20) The geometrical conditions at the lower ends of vials are shown on a larger scale in FIGS. 1a and 2b. It is clearly evident that a transition region is formed between the cylindrical side wall 2 extending in the axial direction and the bottom 3 extending perpendicular thereto, i.e. in the supporting position in horizontal direction. For the purposes of the present invention, this transition region 8 is considered as an edge portion, which is located outside the actual base of the vial 1, if viewed in the longitudinal direction of the vials wherein this base is defined as the contact surface of a vial 1 when resting on a flat surface. If the bottom 3 of a vial 1 is flat, as shown in FIG. 2a, this contact surface is circular and represents the bottom-most portion of a vial 1, if viewed in an axial longitudinal section. If the bottom of a vial 1 is concavely curved as shown in FIGS. 1a and 1b, this contact surface is annular and formed by the vertices 9 of the base 3 of the vial 1. These vertices form a ring along the edge of the base 3, if the vial 1 is viewed from below.

(21) As can be seen in particular in FIG. 2b, this transition region 9 or edge portion is disposed between the bottom 3 or the base and the cylindrical side wall 2 of the vial 1 and is thus clearly separated from these two portions. While in the embodiment of FIG. 2a the cylindrical side wall 2 and the bottom 3, at least at the edge of the vial, is flat, the transition region or edge portion 8 is evenly curved with a uniform radius of curvature r2.

(22) Because of the very tight tolerances that need to be fulfilled particularly at the lower ends of vials this transition region or edge portion 8 has an exactly predetermined geometry, and according to the present invention this exact geometry is used for matching the geometry of retaining protrusions 15 at the lower ends of the side walls 14 of the receptacles of the supporting structure exactly to the geometry of the transition regions or edge portions 8 of the vials. More specifically, the retaining protrusions 15 are formed such that these cooperate only with the transition regions or edge portions 8 of the vials and thus only within the aforementioned well-defined transition regions between the cylindrical side walls 2 and the bottom 3. In other words, the retaining protrusions 15 cooperate exclusively with portions of the vials outside of the respective base, but these do not cooperate with the cylindrical side wall 2.

(23) Generally, the retaining protrusions 15 may support or hold these transition regions or edge portions by a positive-fit or by friction. However, the present invention prefers a purely positive-fit supporting of the transition regions or edge portions 8 by the retaining protrusions 15, for which purpose it is sufficient that the retaining protrusions 15 protrude in radial direction sufficiently far into the apertures or receptacles of the supporting structure for preventing that the vials slip through downward. Surprisingly, an evaluation of the typical geometry at the lower ends of vials but also of other pharmaceutical containers, such as cartridges, has revealed that it is possible to form retaining protrusions 15 of a suitable material with sufficiently tight tolerances, so that such a supporting can be ensured in a reliable manner.

(24) As shown in FIG. 2b, retaining protrusions 15 provided at the lower ends of the apertures or receptacles of the supporting structure protrude inward in radial direction into the apertures or receptacles for supporting the vials in cooperation with the transition regions or edge portions 8 of the vials in such a manner that bottoms of the vials, or more generally the lower ends of the vials, jut out of the apertures or receptacles and are thus are freely accessible from the lower side of the carrier. This support is shown overall in FIG. 2a. Shown is a generally tubular receptacle 12 formed by a circumferential side wall 14 of the supporting structure (not shown). The side wall 14 may extend vertically downward (as shown schematically in FIG. 2a), but may also be inclined uniformly by a relatively small angle relative to a central perpendicular line to extend inward in radially radial direction. This angle may, for example, be in the range between about 1 degree and about 3 degrees, more preferably between about 1 degree and about 2 degrees, in particular for enabling a deforming of the supporting structure from a mold used for manufacturing the same using an injection molding process. At the lower edge of the side wall 14, a retaining protrusion 15 is formed, as shown on a larger scale in FIG. 2b. Is clearly visible that the bottom 3 of the vial 1 protrudes beyond the lower edge of the side wall 14, wherein, however, the transition region or edge portion 8 of the vial is supported sufficiently in order to support the total weight of the vial 1, including the content and a closure (each not shown) and to prevent slippage of the vials 1 out of the receptacle 12. In FIG. 2a, it is also clearly visible that for the supporting according to the present invention a gap is formed between the inner surface of the side wall 14 and the outer surface of the cylindrical side wall 2 of the vial 1, which enables a friction-free insertion of the vial 1 into the receptacle 12 from above and an axial displacement of the vial 1 inside the receptacle 12 with very low forces.

(25) The geometric relationships of the supporting of the transition region or edge portion 8 on the at least one retaining protrusion are shown in FIG. 2c on a larger scale for an embodiment of a vial having a planar bottom 3. This drawing also shows the tolerances and dimensions in millimeters for 2R-vials to 4R-vials and mathematical formulas for the dependency of important values of tolerances and geometric parameters are indicated.

(26) Corresponding considerations of the tolerances can be made for vials of other sizes, as summarized in the following Table 2:

(27) TABLE-US-00002 TABLE 2 results of considerations of tolerances for vial of different sizes convexity (dimensions in mm) tray vial nominal nominal inner maximum minimum dimension consideration diameter of diameter diameter of vial of tolerances nest at of nest at of nest at diameter maximum minimum maximum minimum radius product convexity tolerances collar collar D1 tolerances diameter diameter fit fit r2 2/4R 16.5 +/0.1 13.6 13.4 16 +0.15/0.15 13.15 12.85 +0.75 +0.25 1.5 6/8/10/15R 22.5 +/0.1 22.6 22.4 22 +0.2/0.2 22.2 21.8 +0.8 +0.2 2 10/15R 24.5 +/0.1 24.6 24.4 24 +0.2/0.2 24.2 23.8 +0.8 +0.2 2 20R 30.5 +/0.1 30.6 30.4 30 +0.25/0.25 30.25 29.75 +0.85 +0.15 2.5 30R 30.5 +/0.1 30.6 30.4 30 +0.25/0.25 30.25 29.75 +0.85 +0.15 2.5

(28) Considerations of tolerances were made for containers of different sizes. The result of such considerations is that the distance by which the retaining protrusions protrude into the apertures or receptacles in radial direction should amount to at least >50% of the r2-value (radius of curvature). The retaining protrusions should be tapered towards their free end (which is of advantage but is not absolutely necessary). The material thickness at the front ends of the retaining protrusions should amount to <50% of the r2-value.

(29) Considering the different geometries of 2R-vials to 30R-vials, it is observed that the bottom radius r2 typically varies from r2=1.5 mm to r2=2.5 mm. Thus, the bottom radius r2 is about 10 times as large as the variation of the outer diameter (0.15 mm to 0.25 mm). A supporting and centering at the bottom radius is thus a technical feature because the tolerances of the outer diameter of the container are much smaller than the contact surface at the bottom edge. The maximum fit in Table 2 is equal to or less than 50% of the bottom radius r2.

(30) The supporting structure can be produced with a sufficient accuracy and in a cost-efficient manner by injection molding, by a deep drawing process or by 3D printing. However, the carrier may also be formed from a fiber-reinforced plastic or a plastic material, to which ceramics or metals are added to increase its thermal conductivity. It is known that fiber-reinforced plastics have a higher thermal conductivity of up to 0.9 W/(m*K) if carbon fibers are added. If ceramics or metals are added to the plastics, the thermal conductivity becomes even larger, resulting in so-called heat-conducting plastic materials. Thus, a thermal conductivity of the material of the supporting structure of up to 20 W/(m*K) may be accomplished.

(31) FIGS. 3a-3b show two examples of a supporting structure 10 according to the present invention in a plan view. The individual apertures or receptacles 12 in the carrier 11 are preferably arranged in a regular array, for example in a matrix arrangement along rows and columns extending perpendicular thereto (FIG. 3a) or along rows intersecting each other at an acute angle (FIG. 3b). This has advantages in the automated processing of the vials, since the vials can be transferred at controlled positions and in a predetermined arrangement to processing stations, for example to processing machines, robots or the like. The separation between the apertures or receptacles may also be implemented by means of individual webs.

(32) FIGS. 3c-3e show three examples for the shape of retaining protrusions 15 of a supporting structure according to the present invention in a plan view. According to FIG. 3c, a single retaining protrusion is formed as a circumferential, radial projection 15 at the lower edge of side wall 14. According to FIG. 3d two retaining protrusions 15 are arranged at equiangular distances to each other and with gaps 16 between them along the bottom of side wall 14. According to FIG. 3e, a plurality of retaining protrusions 15 are arranged at equiangular distances to each other and with gaps 16 formed therebetween along the lower edge of side wall 14, which enables a certain flexibility of the retaining protrusions 15 in a simple manner.

(33) By selection of the material and thickness of the retaining protrusions 15, these can be set to be sufficiently stable for supporting the vials reliably at their edge portions while preventing a slipping through of the vials in a reliable manner. However, the specific shape of the retaining protrusions 15 also has an effect on the supporting force of the retaining protrusions that can be accomplished.

(34) Generally, the surface 17 of the retaining protrusions 15 facing the transition region or edge portion 8 may be inclined toward the bottom of the carrier at a predetermined angle relative to a line perpendicular to a plane spanned by the carrier, as shown in FIG. 2c, wherein the angle is specifically matched to the geometry of the container to be supported at its lower end, but is usually about 45 degrees, and conveniently lies in a range between 10 degree and 70 degrees, more preferably in the range between 20 degrees and 50 degrees.

(35) Generally, the surface 17 of the retaining protrusions 15 facing the transition region or edge portion 8, however, may also be curved, particularly concavely curved, with a radius of curvature r2 which basically corresponds to the aforementioned bottom radius r2 of the vial to be supported.

(36) As shown in FIG. 2d, for further reinforcing the retaining protrusions 15 additional straight portions 18a may be formed at the front ends of the retaining protrusions 15 extending perpendicular to a plane spanned by the carrier, i.e. in the longitudinal direction of the vial to be supported, wherein the axial length of the straight portions 18a in a direction perpendicular to the plane spanned by the carrier then essentially determines the bending rigidity of the retaining protrusions 15. Conveniently, this axial length may be in the range of 0.1 to 5.0 mm, preferably in the range of 0.1 to 2.0 mm.

(37) FIG. 4a shows a supporting structure 10 according to a first embodiment of the present invention in a side view. This supporting structure 10 is generally formed as nest having a plurality of tubular receptacles for accommodating the vials, preferably for accommodating the vials completely or over their entire length, and comprises an upper supporting flange 20, which is followed by the upper side wall 21 with a horizontal step 22 at its lower edge. The tubular receptacles for accommodating the vials extend vertically downward from this step 22. The space formed by the upper side wall 21 may be trough-shaped. When the upper ends of vials accommodated in the receptacles project into this space, the upper ends can be gripped in a simple manner, for example, by robots or gripping devices so that the vials can be removed from the receptacles toward the upper end or so that the vials can be inserted into the receptacles from above.

(38) As shown in FIG. 4a, slots 24 may be formed at the lower ends of the side walls 23 which are aligned with each other in predetermined directions, e.g. along a direction perpendicular to the longitudinal side of the supporting structure 10, as shown in FIG. 4a. In this manner, e.g. strip-shaped height adjusting devices may engage into the slots 24, which are disposed below the bottoms of the vials and in alignment with these slots 24 for lifting or lowering the vials suitably by adjusting the height. Or the slots 24 permit a flexing of the supporting structure 10, and thereby an expansion of the lower ends of the receptacles whereby the vials may be brought out of engagement downward.

(39) FIG. 4b shows the accommodation of such a supporting structure 10 in a trough-shaped transport and packaging container 50 (also named as so-called tub hereinafter). The transport and packaging container 50 comprises a closed bottom 51, a circumferential side wall 52 extending substantially perpendicular to bottom 51, which is followed by horizontal step 53 on which the upper supporting flange 20 of the supporting structure 10 is supported, an upper side wall 54, which is inclined relative to a line perpendicular to the bottom 51, and a flange 55 at the upper rim. The transport and packaging container 50 may be sealed by means of a protective film or a packaging film bonded on the upper rim 55. The protective film may be, in particular a gas-permeable plastic film, in particular a web of synthetic fibers such as polypropylene fibers (PP), or a Tyvek protective film, which enables the sterilization of the vials accommodated and packaged in the supporting structure 10 via the film.

(40) FIG. 5 shows a supporting structure 10 according to a second embodiment of the present invention in a perspective top view. This is formed as a flat supporting plate 11 of a relatively small thickness, preferably made of a plastic material, as described above. The apertures in the supporting plate 11 are formed as through holes 12, at the lower ends of which the retaining protrusions 15 are formed in the afore-mentioned manner, preferably integrally with the supporting structure 11 for sufficiently supporting the vials. If a lateral (radial) guidance is desired, and in particular if a collision of vials, which are supported in directly adjacent apertures 12, is to be prevented, guiding members 28 in the form of pins, plates or the like may be provided on the upper side of the supporting plate 11 at least in sections along edges of the apertures 12, which guiding members extend perpendicular to the upper side of the supporting plate 11.

(41) FIGS. 6a-6d show examples of the use of a supporting structure according to the present invention in a freeze-drying process, in each case in a schematic side view.

(42) According to FIG. 6a, the cooling surface 30 is planar. The bottoms of the vials 1 are in direct contact with the upper side of the cooling surface 30. Conveniently, the supporting structure 20 rests on the upper side of the cooling surface 30 so that the vials 1 rest freely on the cooling surface 30. Of course, the supporting structure 20 may also be lifted relative to the cooling surface 30 by a small distance as long as the direct contact of the bottoms of the vials 1 with the upper side of the cooling surface 30 is ensured.

(43) According to FIG. 6b, the bottoms 3 of the vials 1 are concavely curved at their centers so that an annular convex gap is formed between the upper side of the cooling surface 30 and the bottoms 3, which may have a beneficial effect on a freeze-drying process. Furthermore, gaps are formed between the side walls 14 of directly adjacent receptacles 12 of the supporting structure into which the cooling fingers 31 project, which surround the receptacles 12 of the supporting structure at least in sections and preferably completely (as circumferential cooling fingers). This may provide an even faster and more effective cooling in a freeze-drying process.

(44) According to FIG. 6c, the bottoms 3 of the vials 1 are concavely curved at their centers, wherein convex projections 33 are formed on the upper side of the cooling surface having a radius of curvature which is matched to the radius of curvature of the bottom 3 in order to ensure a direct contact between the bottom 3 and the upper side of the cooling surface 30.

(45) According to FIG. 6d, the bottoms 3 of the vials 1 are concavely curved at their centers, wherein concave depressions 34 are formed on the upper side of the cooling surface for reducing the thermal contact in this region, which may have a beneficial effect on a freeze-drying process.

(46) FIG. 7a shows an example of the use of a supporting structure according to the present invention for the internal cleaning of a vial 1, which is accommodated in a receptacle 12 of the supporting structure (not shown). For this purpose, a nozzle or pipe 40 is inserted by means of a height adjustment device 41 via the filling opening 7 into the interior of the vial 1 to spray a cleaning liquid (in this case water) into the vial 1. After this cleaning step the vial 1 is dried and then filled with a substance or liquid.

(47) FIG. 7b shows as a further example of the use of a supporting structure according to the present invention the cleaning of the outer surfaces of a vial 1, which is accommodated in the receptacle 12 and supported on the retaining protrusions 15. By means of a lower spraying device 43, a cleaning fluid, preferably a cleaning liquid, such as water or a water steam, is sprayed from below against the bottom of vial 1. If this is performed with a sufficient intensity the vial 1 can be lifted off the retaining protrusions 15, so that the vial 1 floats freely in the receptacle 12 (levitation). Thereby a flow is formed temporarily in an annular gap between the outer wall of vial 1 and the inner surface of side wall 14, which flows over the outer surface of the vial 1 and cleans it. The flow exits again at the upper end of the receptacle 12. If the intrusion of the cleaning liquid into the interior of the vials is to be prevented 1, the filling aperture 7 of the vial 1 will be closed beforehand, for example by means of a plug. Alternatively or at the same time, a cleaning fluid, preferably a cleaning liquid, such as water or a water steam, may also be sprayed from the top into the receptacle 12 by means of an upper spraying device 42. In the case of a simultaneous spraying both from below and from above, the fluid flow from the lower end should in any case be more intense than the fluid flow from the top to a sufficient extent, preferably such that the bottom of the vial 1 is lifted off the retaining protrusions 15 so that the vial 1 floats freely in the receptacle 12 (levitation).

(48) FIG. 7c shows a further example of the use of a supporting structure according to the present invention during lifting and lowering of the vials in receptacles of the supporting structure, and for drying the outer surfaces of the containers.

(49) By means of a lower spraying device 43, a gas, for example nitrogen, is blown against the bottom of the vial 1 from the lower end. If this is performed with a sufficient strength the vial 1 can be lifted from the retaining protrusions 15 so that the vial 1 floats freely in the receptacle 12 (levitation). Thereby a gas flow is formed temporarily in the annular gap between the outer wall of the vial 1 and the inner surface of the side wall 14, which flows over the outer surface of the vial 1 and thus dries it. The gas flow exits again at the upper end of the receptacle 12. If the intrusion of the gas into the interior of the vial 1 shall be prevented, the filling opening 7 of the vial 1 will be closed beforehand, for example by means of a plug. Alternatively or at the same time a gas, for example nitrogen may also be blown into the receptacle 12 from above by means of an upper spraying device 42. In the case of simultaneous injection of gas both from below and from above, the gas flow from the bottom should in any case be more intense than the gas flow from the upper end to a sufficient extent, preferably such that the bottom of the vial 1 is lifted from the retaining protrusions 15 so that the vial 1 floats freely in the receptacle 12 (levitation) and so that all portions on the outer surface of the vial 1 can be dried.

(50) FIGS. 7d and 7e show the treatment of vials according to FIGS. 7b and 7c, wherein so-called press-fit caps are placed on the upper ends of the containers 1, which cover the filling openings but continue to ensure that the interior of the vial 1 is in communication with the gas environment in a first position so that moisture and vapors may exit via the cap into the environment during a freeze-drying process. Only if the caps are pressed completely downward into a second position, this communication no longer exists so that the interior of the vial is then sealed gas-tight against the environment. The caps are thus pressed completely downward after the actual freeze-drying process. During the freeze-drying process the caps are in the first position.

(51) According to FIG. 8, the injection of a gas or fluid from above into the receptacles 12 may also be used in order to push the vials 1 downward and out of the receptacles 12, wherein the supporting force exerted by the retaining protrusions 15 must be overruled. To mitigate this supporting force, the carrier of the supporting structure may be bent suitably to expand the lower ends of the receptacles 12 appropriately. This expansion may be performed to such a degree that the aperture widths of the retaining protrusions 15 is larger than a maximum outer dimension of the vials 1 so that the vials 1 can also be removed out of the receptacles 12 downward without any friction. In this case, slots 24 at the lower ends of the receptacles 12 may enhance the bending of the supporting structure (see FIG. 4a), as stated above.

(52) FIG. 9 shows a schematic flow diagram of a method according to the present invention for the treatment of vials for substances for pharmaceutical or medical applications.

(53) In step S1, a transport and packaging container (cf. FIG. 4b) is fed and then introduced into a sterile processing environment, and then a protective film is peeled off from the upper rim thereof. In step S2, the vials are then released. Before the vials are filled with a substance or liquid, the vials may be weighed (optional step). Subsequently, in step S3, the vials are filled while they are supported on the supporting structure. The supporting structure may still be accommodated in the transport and packaging container, as shown in FIG. 4b. In step S4, the vials are then released again. After the filing of the containers with a substance or fluid, they can be weighed again (optional step).

(54) In step S5, plugs or special stoppers (e.g. press-fit caps) are inserted into the filling openings of the vials for sealing. If a freeze-drying process shall be performed afterwards, press-fit caps will be inserted into the filling openings, which cover the filling openings for preventing the intrusion of contaminants but ensure at the same time that the inner volumes of the vials are still in communication with the environment via the press-fit caps. Such caps are shown in FIGS. 7d and 7e.

(55) Optionally, the vials may also be inserted into the receptacles or apertures of the supporting structure at this time to be further treated while being supported at the supporting structure.

(56) In step S6, the supporting structure together with the vials supported at it is placed in a freeze-dryer. Subsequently, in step S7, a freeze-drying process is performed, which is, however, not mandatory. In any case, the vials are sealed against the environment in a gas-tight manner by pressing the press-fit caps downward after the freeze-drying (lyophilization) step S7.

(57) The supporting structure is then removed again from the freeze-drier in step S8. Here, the vials remain to be accommodated in the receptacles of the supporting structure.

(58) In step S9, metal caps are crimped onto the upper ends of the vials with the closure plugs or caps (optional step). Here, the vials remain to be accommodated in the receptacles of the supporting structure.

(59) In step S10, a cleaning of the outer surfaces of the vials is performed. Here, the vials remain to be accommodated in the receptacles of the supporting structure. The cleaning step is carried out as described above with reference to FIG. 7b.

(60) In step S11, a drying the outer surfaces of the vials is performed. Here, the vials remain to be accommodated in the receptacles of the supporting structure. The drying step is carried out as described above with reference to FIG. 7c, or alternatively by applying heat, in particular by application of infrared radiation.

(61) Afterwards, the vials may be labeled or marked in step S12. Here, the vials remain to be accommodated in the receptacles of the supporting structure. Or the vials are removed from the receptacles of the supporting structure beforehand, as described above, in particular with reference to FIG. 7c.

(62) TABLE-US-00003 LIST OF REFERENCE NUMERALS 1 vial 2 cylindrical side wall 3 bottom 4 neck portion 5 constricted neck portion 6 upper rim 7 filling opening 8 transition region/curved portion 9 vertex of base of a vial 10 supporting structure 11 carrier plate 12 aperture/receptacle 13 recess for access 14 side wall of receptacle 12 15 retaining protrusion 16 gap 17 slope 18 front end 18a straight portion 19 connecting portion 20 upper supporting flange 21 upper side wall 22 step 23 lower sidewall 24 slot 28 pin 30 cooling surface 31 cooling finger of cooling surface 30 32 nip to bottom 3 of container 1 33 protrusion on cooling surface 30 34 depression on cooling surface 30 40 injection nozzle 41 height adjustment device 42 upper spraying device 43 lower spraying device 50 transport and packaging container 51 bottom 52 bottom sidewall 53 step 54 upper side wall 55 flange lz length of straight portion