Device for aligning and closing syringes, cartridges and vials in a filling system

Abstract

The present invention relates to a primary packaging holder (100) for aligning a primary packaging, e.g. a syringe, cartridge or vial, along its longitudinal axis relative to a first system axis and relative to a positioning axis (Z) of the primary packaging holder, and for holding the primary packaging in a defined position, wherein the primary packaging holder has at least one receiving device with at least one positioning contact surface (111) and at least one alignment contact surface (112, 122), wherein the positioning contact surface (111) and the alignment contact surface can be brought into contact with the outer surface of a primary packaging to be received in the primary packaging holder.The primary packaging holder can be part of an arrangement comprising a guide rail and at least one primary packaging holder, wherein the arrangement can further include a closure device for closing the primary packaging. In one method, this arrangement can be part of a filling system in which a closure element, in particular a stopper, can be inserted at a predefined position in the receiving volume of a pre-filled primary packaging, preferably a primary packaging pre-filled with a pharmaceutical composition, such as a syringe, cartridge, or vial, in order to close the primary packaging, wherein in particular a predefined air space can be formed between the composition and the closure element.

Description

[0001] The present invention relates to a primary packaging holder (hereinafter referred to as PH) for aligning a primary packaging (hereinafter referred to as PM), e.g., a syringe, cartridge, or vial, along its longitudinal axis relative to a first system axis and relative to a positioning axis of the PH, and for holding the PM in a defined position. The PH comprises at least one receiving device with at least one positioning contact surface (hereinafter referred to as PKF) and at least one alignment contact surface (hereinafter referred to as AKF), wherein the PKF and the AKF can be brought into contact with the outer surface of a PM to be received in the PH. The PH can be part of an arrangement comprising a guide rail (hereinafter referred to as FS) and at least one PH, wherein the arrangement can further include, in particular, a closing device for closing a PM.In an associated process, this arrangement can be part of a filling system in which a closure component, in particular a stopper, can be inserted into a pre-filled PM - in particular the PM can be a PM pre-filled with a formulation containing a pharmaceutical composition, e.g. a pre-filled syringe, pre-filled cartridge or pre-filled vial - at a predefined position in the receiving volume of the PM in order to close the PM, whereby in particular a predefined air space can be formed between the composition and the PM.

[0002] In the prior art, holders for primary packaging materials, such as syringes, are offered by various suppliers. These holders are composed of different components that grip and clamp the syringe body, allowing the syringe to be positioned in a filling and stoppering system. Such holders are compatible with various filling systems and are generally coordinated with the system's layout. The primary packaging holder itself can be adapted to different primary packaging geometries, such as syringes, vials, and cartridges, enabling these to be accommodated in the holder and subsequently used in a further arrangement, device, and / or system.These holders, arrangements, devices and / or systems are generally suitable and intended for automated filling and automated sealing of primary packaging.

[0003] These brackets must be precisely aligned during closing, especially when inserting the plug, to ensure proper sealing of the PM with the VB.

[0004] The tolerance depends on the combination of the primary packaging (PC) and the primary packaging (PM) and may require alignment accurate to a tenth of a millimeter (e.g., when inserting a stopper into a syringe). With some holders, the screws of the transport unit, into which the primary packaging holder is inserted, may need to be tightened to varying degrees. This can cause the primary packaging holder to shift from its intended position, particularly vertically (up / down), tilt, or rotate. The entire holder can also shift or slip to the left or right, affecting the positioning and alignment of the PM, especially the centering of a syringe.If the position and / or orientation is incorrect, and / or the PM (this applies particularly to a syringe) is only slightly offset from the filling tube or positioned at an angle to the filling tube in the holder, vacuum loss or other undesirable effects can occur when inserting the closure component into the PM, especially when inserting the stopper into the syringe. This can lead to the closure component not being positioned correctly, e.g., the stopper not being inserted into the correct position in the syringe. The position of the closure component in / on the PM, especially the stopper position, in the syringe, cartridge, cartridge, or vial, is incorrect. Furthermore, the seal and thus the sterility may be compromised, which can endanger patient safety.

[0005] Improperly sealed syringe bodies, manufactured and filled with a formulation containing a compound, must be disposed of because they do not meet quality criteria. Depending on the batch (closure / stopper) and orientation, rejection rates of up to 30% can occur. This results in a significant financial burden. The filled formulation containing a compound, the packaging material, and the manufacturing costs add up to an enormous expense. Added to this are the costs for the proper disposal of the substandard filled and manufactured syringe bodies, especially those with improper seals.

[0006] To minimize these losses, the primary packaging holder and the method for inserting the stopper (stopper insertion) at a predefined position in a primary packaging medium such as a syringe, vial, or cartridge—particularly as part of the manufacturing process—have been optimized and made more robust. The technical solution of the present invention perfects the alignment of the closure device (hereinafter abbreviated as CD)—the insertion tube / plunger—with respect to the longitudinal axis of the primary packaging medium, or conversely, the alignment of the primary packaging medium with its longitudinal axis with respect to the insertion tube / plunger / closure device—particularly for a primary packaging medium in the form of a syringe—and ensures that the alignment is performed consistently and correctly, regardless of the person performing the operation.

[0007] Therefore, a first aspect of the present invention is a primary packaging holder for receiving a primary packaging (PM), wherein the primary packaging holder (PH) is configured to receive a primary packaging (PM) that has an outer surface and a receiving volume extending at least partially along a longitudinal axis with at least one first opening, wherein the first opening of the receiving volume of the primary packaging (PM) can be closed by means of a closure element which can be inserted / is inserted into the first opening along the longitudinal axis of the receiving volume, wherein the primary packaging holder is configured for arrangement in a system for closing the primary packaging, wherein the primary packaging holder (PH) has a first positioning axis and is configured toto receive the primary packaging material in the primary packaging holder at a defined position along the first positioning axis and with a defined orientation of the longitudinal axis of the receiving volume of the primary packaging material (PM) relative to the first positioning axis, wherein the primary packaging holder has at least one receiving device and the at least one receiving device for receiving the primary packaging material in the primary packaging holder at the defined position along the first positioning axis has at least one first PKF and for receiving the primary packaging material with a defined orientation of the longitudinal axis of the receiving volume relative to the first positioning axis in the primary packaging holder has at least one AKF, wherein the first positioning contact surface can be brought into contact with a first section of the outer surface of a primary packaging material to be received by the primary packaging holder.in particular over a surface, and wherein the at least one activated carbon filter (ACF) can be brought into contact with a second section of the outer surface of a primary packaging material to be received by the primary packaging holder, in particular over a surface.

[0008] According to one embodiment of the first aspect of the present invention, the PH (primary packaging holder) is provided for receiving primary packaging materials such as a syringe, cartridge or vial (for examples of primary packaging materials see Fig. 14a-14g), wherein the PH is designed in particular to receive a primary packaging material such as a syringe, cartridge or vial, which has an outer surface and a receiving volume extending at least partially along a longitudinal axis, in particular in a range of 0.2 to 200 ml with at least one first opening, wherein the first opening of the receiving volume of the primary packaging material, in particular the syringe, cartridge or vial, is closed by means of a closure component suitable for the primary packaging material, e.g. the syringe, cartridge or vial, e.g.a stopper, is closable, wherein the closure component can be inserted / is inserted into the first opening along the longitudinal axis of the receiving volume, wherein the PH is designed for arrangement in a system for closing the syringe, cartridge or vial, wherein the PH has a first positioning axis and is designed to receive the primary packaging material with a defined position along the first positioning axis and with a defined orientation of the longitudinal axis of the receiving volume of the syringe, cartridge or vial in the PH relative to the first positioning axis, wherein the PH has at least one receiving device and the at least one receiving device (clip, holding arm, gripping arm, bridge, etc.) for receiving the primary packaging material in the PH at the defined position along the first positioning axis has at least one first PKF - e.g.an (inner) surface of a clip, holding arm, gripping arm, bridge, contact surface of a clip or the like, on which the flange of the syringe can rest - and for receiving the primary packaging material (e.g. a syringe, cartridge or vial) with a defined orientation of the longitudinal axis of the receiving volume relative to the first positioning axis (Z) in the PH, at least one ACF - e.g. a holding arm, clip or any suitable surface thereof, which can align the primary packaging material, e.g. a syringe, cartridge or vial, in the desired position - wherein the first ACF can be brought into contact with a first section of the outer surface - e.g. the underside of a flange or edge of the primary packaging material, e.g. of the syringe or cartridge - of a primary packaging material (syringe, cartridge or vial or the like) to be received by the PH, in particular over a surface area, and wherein the at least one ACF can be brought into contact with a second section of the outer surface - e.g.a part of the outer surface of the primary packaging material (syringe / cartridge / vial etc.) - of a primary packaging material (syringe, cartridge or vial or the like) to be absorbed by the PH, can be brought into contact, especially over a large area.

[0009] A primary packaging holder according to the invention enables a defined position of the packaging material along a first axis in a system (in particular along a first system axis) and an orientation in space. The axis along which the position of the primary packaging material (in the system) is / can be aligned can be selected, in particular depending on the system in which the primary packaging holder is installed, in order to achieve the correct orientation of the primary packaging material in each case. By including the primary packaging support (PKF) and the primary packaging support (AKF), the position of the primary packaging material along a first axis, i.e., along a defined axis, and its orientation in space are defined simultaneously, wherein the system axis along which the position and orientation of a primary packaging material is defined can be selected depending on the specific system.A PH according to the present invention enables flexible and reproducible positioning of a PM in the x and / or y direction within the system, as well as the necessary alignment of the longitudinal axis of the PM's receiving volume with respect to a selected system axis. The system axis to which the PM is to be positioned and / or aligned can vary depending on the system type and category (e.g., filling of formulations containing a pharmaceutical composition, a system for filling formulations containing a cosmetic composition, or a system for filling food products—each as defined herein).

[0010] In a further embodiment of a primary packaging holder (PH) according to the invention, the PH is configured to receive the PM such that, in a properly received state, at least one first section of its outer surface rests against the at least one first PKF and at the same time at least one second section of its outer surface rests against the at least one AKF. A first section of the outer surface can, in particular, be the underside of a full-circumference (i.e., completely circumferential) flange or a partially circumferential rim in the form of wings of a syringe, or the underside of a rim of a vial or cartridge, or a section or part thereof.The second section of the outer surface may in particular be the outer surface or a section or part of the outer surface of a primary packaging material, in particular the outer surface or a section or part of the outer surface of a syringe, cartridge or vial.

[0011] The inclusion of at least one positioning sensor (PKF) and at least one automatic positioning sensor (AKF) achieves the specific technical effect of simultaneously positioning the PM along the first positioning axis and aligning it correctly. The PKF maintains the selected or aligned position of the PM, with the PKF in contact with at least one section of the PM's outer surface. This mutual contact maintains the achieved position. This position is influenced by the at least one automatic positioning sensor before, after, and / or during the PKF's application. The automatic positioning sensor rests against at least one further section of the PM's outer surface and aligns (pushes, pushes), i.e., corrects any inclination of the PM relative to the first system / positioning axis and brings it into a correct position.The position thus achieved is maintained by at least one primary packaging filter (PKF) and / or activated carbon filter (AKF). In particular, an inclination of the longitudinal axis of the primary packaging material and / or of the longitudinal axis of the receiving volume of greater than or equal to 0.01° (degrees) to the first system axis / positioning axis up to and including 2° is tolerable.In particular, an angular deviation of the orientation of the PM's longitudinal axis relative to the first axis / system axis within this order of magnitude is tolerable, preferably an inclination of ≤ 1.9°, ≤ 1.8°, ≤ 1.7°, ≤ 1.6°, ≤ 1.5°, ≤ 1.4°, ≤ 1.3°, ≤ 1.2°, ≤ 1.1°, ≤ 1.0°, ≤ 0.9°, ≤ 0.8°, ≤ 0.7°, ≤ 0.6°, ≤ 0.5°, ≤ 0.4°, ≤ 0.3°, ≤ 0.2°, ≤ 0.1°, ≤ 0.09°, ≤ 0.08°, ≤ 0.07°, ≤ 0.06°, ≤ 0.05°, ≤ 0.04°, ≤ 0.03° or less than or equal to 0.02°.Accordingly, in a preferred embodiment, the primary packaging holder is designed to accommodate a primary packaging material in such a way that an angular deviation of the alignment of the longitudinal axis of the PM relative to the first axis / the system axis lies within a previously described, defined tolerance range.

[0012] In a further embodiment of a primary packaging holder PH according to the invention, the PH is designed to receive the PM in such a way that, in a properly received state of the PM by the PH, the longitudinal axis of the receiving volume of the PM extends along the first positioning axis of the PH.

[0013] This embodiment ensures that the PM is aligned within the system via the PH, thereby guaranteeing precise sealing of the PM with a VB, particularly the insertion of the plug, along the longitudinal axis of the PM's receiving volume. Thus, in an inventive method for (automated) sealing with, in particular, constant (preset parameters (e.g., vacuum, speed, temperature, VB material, etc.), whereby a person skilled in the art can adapt and specify the process parameters for each PM, especially the pre-filled PM), the same forces are exerted on each PM and / or VB at the VV during sealing. Therefore, each PM of the same type (geometry, material, coating, etc.) with the same VB is reproducibly sealed against a resistance reproducibly generated when the VB is inserted into the first opening of the PM (e.g.,...).by compressing the VB), along the longitudinal axis of the PM, inserting it into the PM's receiving volume. This reproducibility allows the VB's position within the PM's receiving volume to be better and more precisely predefined and, using the process parameters in the PM sealing procedure, reliably, reproducibly, and automatically. This results in a predefined air space. The predefined air space is product- and process-specific and can be zero, i.e., non-existent, in cases where the product, without an air space, i.e., the sealing component (e.g., a stopper), is intended to directly contact the liquid formulation. In this case, for example, the stopper is in direct contact with the formulation, particularly a liquid of a predefined viscosity containing a specific composition. Alternatively, in other cases, it may be several millimeters to centimeters away from the formulation.The PM must be inserted with a gap (and a resulting air space) to the formulation. In any case, the PM must not be closed at an angle or tilt (e.g., the lip of the VB is not pinched) outside of the tolerances / inclinations defined herein, where the VB is inserted into an impermissible position and / or orientation within the PM. An impermissible position and / or orientation of the VB within the PM can lead to potentially undesirable contact (depending on the predefined product and process) between the pre-filled formulation containing a composition and the VB material, resulting in leakage. Leaks can lead to the formulation containing a composition spilling out and / or to contamination of the sterilely filled formulation containing a composition with microorganisms or its components, etc. Inadequate sealing can compromise sterility.If this is detected, the product must be destroyed and disposed of immediately. Otherwise, patient safety is potentially compromised. Furthermore, with a primary packaging material that is (incorrectly) sealed in this way (e.g., an incorrectly sealed syringe, cartridge, vial, etc.), proper use, such as controlled manual dispensing of the formulation from a syringe or cartridge, or manual / automated dispensing from a delivery or injection system, can no longer be guaranteed. In such cases, the stopper may no longer slide, the delivery or injection system may not be assembled correctly, or the dispensing mechanism may malfunction (blocked, error message, etc.).

[0014] Especially for formulations containing a pharmaceutical composition – as defined herein – maintaining sterility is the most important quality characteristic of the product obtained after sealing the pre-filled PM (product = pre-filled PM, sealed with VB and sterile). Similarly, for packaged foods and dietary supplements, shelf life must be maintained in compliance with hygiene regulations or Good Manufacturing Practice (GMP), and preservation must be ensured as a quality characteristic. The same applies to cosmetics.

[0015] In a further embodiment of a primary packaging holder PH according to the invention, the PH is designed to be positioned and aligned in such a defined manner in a system, in particular in a system comprising a closure device (e.g. a filling system, preferably an aseptically operated filling system, in particular comprising a closure device), that in a properly installed state of the PH in the system the first positioning axis of the PH coincides with a first system axis, in particular is aligned with it.

[0016] Such a system can in particular be a filling system for filling and sealing the PM, wherein the PH can be correctly positioned and aligned in particular relative to a VV which is designed for (automated) sealing of a PM received by the PH.

[0017] This makes it possible to achieve with the PH that, if it is positioned and aligned in a system in such a way that the first positioning axis of the PH coincides with the first system axis, in particular is aligned with it, the longitudinal axis of the intake volume of a PM taken up by the PH coincides with the first system axis.

[0018] The first axis of the system can in particular coincide with a linear direction of movement of a VV, which is designed to move a VB along this direction of movement, in particular during a closing process of a PM, wherein the first axis of the system can in particular coincide with an insertion direction of the VB, along which the VB can be inserted into the PM to close a PM.In this case, it can be achieved by means of a PH designed as described above that, if it is positioned and aligned in a system in such a way that the first positioning axis of the PH coincides with the first system axis, in particular is aligned with it, the longitudinal axis of the receiving volume of a PM received by the PH coincides with the first system axis and thus with the direction of movement of the closure device and in particular with the insertion direction of the VB, so that the VB can be correctly inserted into the receiving volume, in particular precisely along the longitudinal axis of the receiving volume of the PM.

[0019] In a further embodiment of a primary packaging holder (PH) according to the present invention, the receiving device has at least one first holding arm (HA) with an outer surface, wherein the first HA extends at least partially in a direction perpendicular to the first positioning axis and part of the outer surface of the first holding arm forms at least partially the first PKF.

[0020] In a further embodiment of a primary packaging holder PH according to the invention, the part of the outer surface of the first holding arm, which at least partially forms the first PKF, is formed by one or more sections of the outer surface of the first holding arm that extend in a plane perpendicular to the first positioning axis, in particular by one or more sections of a top surface of the first holding arm.

[0021] In this embodiment, the portion of the outer surface of the first holding arm (i.e., the surface facing the PM) that forms the first positioning surface (PKF) is formed, in particular, by one or more sections of the outer surface of the first holding arm extending in a plane perpendicular to the first positioning axis, specifically by one or more sections of an upper surface of the first holding arm. The PM can rest on the upper surface of the holding arm with its rim, preferably a PM received by the PH, such as a syringe, cartridge, or vial, with an underside of its upper rim or flange resting on this upper surface of the holding arm. In the case of cartridges, the rim is also called a crimped rim and is equally suitable as an rim within the meaning of the invention to form a first section of the outer surface of the PM and to serve for positioning, and in particular to be brought into contact with the PKF of a PH.

[0022] In a further embodiment of a primary packaging holder PH according to the invention, at least one further section of the outer surface of the first holding arm forms at least part of the at least one activated carbon filter (ACF). In one embodiment, one section of the outer surface of the first holding arm is the one on which the upper edge of the primary packaging rests, and the further section of the outer surface is the one against which the lateral surface of a primary packaging rests.

[0023] In one embodiment, one or more sections of the outer surface of the first and / or second holding arm combine two functions. One function is to align the PM, and the second function is optionally to hold the PM in the PH, so that the PM is aligned and held in its correct position. The second holding function can be implemented separately in a separate component, which contributes to the alignment of the PM. In another embodiment, there can also be a component that only aligns (e.g., a variant of the bridge) but does not perform the function of holding the PM. The components can be present in any combination. Thus, the PH described here is suitable for a flexibly deployable (adaptable to different PMs) filling system, which is designed or can be designed for filling a large number of different PMs (such as the "Optima Multiuse system").

[0024] In a further embodiment of a primary packaging holder PH according to the invention, the receiving device has one or more holding arms, wherein in particular a first HA has at least one first component designed separately and as a positioning element, in particular e.g. a "Y-clip" (a Y-shaped insert, in particular a Y-shaped holding element, optionally with additional clamping and / or alignment function), wherein the first component in particular forms a first holding element or a part thereof, wherein a section of the outer surface of the positioning element forms at least partially the first PKF, wherein the positioning element is in particular arranged in the receiving device such that the section of the outer surface of the positioning element, which forms at least partially the first PKF, extends in a plane perpendicular to the first positioning axis.

[0025] In a further embodiment of a primary packaging holder PH according to the invention, the receiving device has one or more holding arms, wherein in particular at least one holding arm, and in the case of several holding arms preferably at least one second holding arm, has at least one second component designed separately and as an alignment element, in particular, for example, a "Y-clip" (a Y-shaped insert, in particular a Y-shaped alignment element, optionally with additional holding and / or clamping function), wherein a section of the outer surface of the alignment element at least partially forms the at least one ACF, wherein the alignment element is in particular arranged in the receiving device such that the section of the outer surface of the alignment element, which at least partially forms the ACF, extends in a direction parallel to the first positioning axis.

[0026] In a further embodiment of a primary packaging holder PH according to the invention, the receiving device described herein, or any other embodiment of the receiving device described herein, has a sufficiently rough surface facing the outer surface of the PM, so that the PM is properly held in the PH. The receiving device may have an anti-slip coating, or the material of the receiving device may be post-processed to a desired roughness, preferably Ra 0.4 µm to less than or equal to Ra 0.8 µm, so that the receiving device has greater frictional resistance on the surface against which the outer surface of the PM is applied.In one version, the receiving device has a coating made of a suitable material that may be used in cleanroom class A and is resistant to disinfecting and / or sterilizing agents such as hydrogen peroxide (H 2 O 2 ), or the receiving device is made of such a material.

[0027] This ensures that the PM does not slip when installed in a system and that the aligned position is maintained during the insertion of the closure component, for example during plug insertion.

[0028] Examples of suitable anti-slip coating materials include silicone, ethylene propylene diene monomer rubber (EPDM), acrylonitrile butadiene rubber (NBR), polyethylene (PE), natural rubber (NR), thermoplastic rubber (TPG), PVC-P, polytetrafluoroethylene (PTFE), bromobutyl, chlorobutyl, vinyl and cork materials, PEEK, and all pharmaceutically permissible materials for a Class A cleanroom (according to the current version of DIN EN ISO 14644-1 or the EC GMP Guide).

[0029] In a further embodiment of a primary packaging holder PH according to the invention, the section of the outer surface of the alignment element, which at least partially forms the at least one activated carbon filter (ACF), is / forms a contact surface, in particular for the second section of the outer surface of the PM, for the defined alignment of the longitudinal axis of the receiving volume of the PM relative to the first positioning axis. In a further embodiment, the outer surface of the PM is the outer surface of a syringe, cartridge, or vial, preferably a syringe.

[0030] In a further embodiment of a primary packaging holder PH according to the invention, the PH is designed such that a position of the first primary packaging element (PKF) along the first positioning axis can be defined, and in particular adjusted, by means of a thickness (extension in the direction of the first positioning axis) of the positioning element – ​​the first component – ​​and thus, in particular, the predefined position along the first positioning axis at which the primary packaging element can be received by the PH. This first component is preferably interchangeable. In particular, the first component can alternatively be inserted into the PH with different thicknesses.The adjustability achieved thereby contributes at least to a flexible adjustment of the PM's receiving position along the PH's positioning axis, and thus in turn to an adjustment of the setting depth / position of the closure component and consequently to an adjustment of the size / volume of the air space between VB and formulation.

[0031] In a further embodiment of a primary packaging holder PH according to the invention, the PH is configured to receive a PM, which has an outer rim projecting radially outwards with respect to the longitudinal axis of the receiving volume of the PM, at least partially surrounding the first opening and having at least one underside extending in one direction, in particular a plane, perpendicular to the longitudinal axis of the receiving volume. In one embodiment, the PM is a syringe, cartridge, or vial, preferably a syringe, the first opening of which has a rim, such as a flange or in the form of wings, wherein the rim is configured such that a sufficiently flat underside is provided with which the syringe, cartridge, or vial, preferably a syringe, can be received into the PH, preferably resting on a first HA.

[0032] In a further embodiment of the primary packaging holder PH according to the invention, the underside of the protruding edge - e.g. flange / wing of a syringe - forms in particular the first section of the outer surface of the PM, with which the first PKF can / is brought into contact for / during the defined positioning of the PM in the PH.

[0033] In a further embodiment of a PH according to the invention, the PH is designed to receive a primary packaging medium - e.g. syringe, cartridge or vial - which has an edge projecting outwards (radially) with respect to the longitudinal axis of the receiving volume of the PM, at least partially surrounding the first opening, with at least one underside extending in one direction, in particular plane, perpendicular to the longitudinal axis of the receiving volume, wherein the underside of the projecting edge - e.g. flange / wing of a syringe - in particular forms the first section of the outer surface of the PM with which the first PKF can / is brought into contact for / during the defined positioning of the primary packaging medium in the primary packaging medium holder.

[0034] In a further embodiment of the primary packaging holder PH according to the invention, the PH is designed to receive a PM whose outer surface has at least one section with a lateral surface or outer surface extending parallel to the longitudinal axis of the PM - e.g., the syringe, cartridge or vial - in such a way that the lateral surface or outer surface of the PM, when the PM is properly received by the PH, rests against the AKF.

[0035] In a further embodiment of a primary packaging holder (PH) according to the invention, the PH is configured to receive a primary packaging (PM) selected from the group comprising: pharmaceutical PMs, cosmetic PMs, or food containers, wherein the group of pharmaceutical PMs includes syringe bodies (synonymous with syringe containers), vials (synonymous with bottles), cartridges, and cartridges. The PMs may be made of glass or polymers – as described herein – and may or may not have surface coatings or treatments. The group of PMs includes syringes, cartridges, vials, and cartridges made of one or more materials, wherein the material used to manufacture a PM is certified according to ISO 9001, ISO 13485, ISO 15378, ISO 45001, EN ISO 13485, and / or EN ISO 15378 in their respective valid versions, and / or such PMs are GMP certified.PMs are also included that fall under the specifications and definitions of the currently valid version of the European Pharmacopoeia (Ph. Eur.).

[0036] The group of pharmaceutical PMs further includes, and preferably, pre-filled / pre-fillable pharmaceutical PMs, including pre-filled / pre-fillable Plajex™< TERUMO syringe bodies, pre-filled / pre-fillable syringe bodies from SCHOTT Pharma, pre-filled / pre-fillable syringe bodies (glass, plastic) from Gerresheimer AG, pre-filled / pre-fillable syringe bodies (glass, plastic) from the Stevenato Group (e.g., Alba®<, Nexa®<, Nexa Flex™<, Fina®< and EZ-fill®<), pre-filled / pre-fillable syringe bodies (plastic syringes) and other PMs from Daikyo Seiko, Ltd. or from SiO2 Medical Products, Inc., Becton, Dickinson and Company (BD) prefilled / prefillable syringe bodies (Hypak™< , Neopak™< ), prefilled / prefillable syrQ BioPure®< glass syringe bodies from SCHOTT Pharma, prefilled / prefillable syrQ BioPure®< silicone-free plastic / glass syringe bodies from SCHOTT Pharma, prefilled / prefillable single-chamber and dual-chamber cartridges from SCHOTT Pharma, prefilled / prefillable single-chamber and dual-chamber cartridges from SCHOTT Pharma, syringes / syringe bodies / containers as in EP3750580A1 (e.g. . Fig. 1, 2 and 7 ) reveals vials or cartridges as in EP3628303A1 (e.g. Fig. 3The invention discloses cartridges from West Pharma, cartridges from Becton, Dickinson and Company (BD) for installation / use in "Liberias™< Wearable Injector", cartridges suitable for installation / use in the SmartDose®< 10 On-Body Delivery System of Westpharma, the cartridges disclosed in EP4243895A1 (e.g. Fig. 12a / b / c) of West Pharma, other PMs suitable for installation in an (automated) application system, and vials of the brand QiremSpeheres™< Microspheres and BioPearl™< Microspheres from TERUMO. For each of the aforementioned prefillable PMs, in particular prefilled with a formulation containing a pharmaceutical composition, the PH according to the invention is suitable for achieving proper alignment of the PM in a system for sealing the PM.

[0037] In a further embodiment of the primary packaging holder (PH) according to the invention, the at least one alignment element – ​​e.g., a retaining arm, a bridge – is designed to receive a PM in such a way that the PM rests against the at least one alignment element with at least one contact surface, in particular with a part of its outer surface – e.g., a section of the outer surface of a syringe, cartridge, or vial – and in particular against its end-surface surface, wherein the alignment element is in particular designed and adapted to the primary packaging to be received such that when the PM rests against its contact surface (e.g.,its outer surface) rests against the alignment element, in particular against its activated carbon filter, in a state of the PH installed in a system with a VV, the longitudinal axis of the receiving volume of the PM is aligned with the first system axis and / or a longitudinal axis of a VB to be inserted into the PM - preferably a plug - and / or with an insertion direction of the VB and / or with a movement direction of the VV - e.g., the setting ear / plunger. In particular, all longitudinal axes involved in an arrangement and in the method for closing (especially the aforementioned longitudinal axes) coincide and run in alignment with each other and lie on a common straight line when the PM is in the predefined position and is properly aligned.

[0038] In a further embodiment of a PH according to the invention, the PH is designed to receive a PM and to be arranged in a system such that the predefined position of the PM for closing is located relative to a position of a VB to be inserted along the longitudinal axis of the VB and is aligned along the first positioning axis, so that the longitudinal axis of the VB, the insertion direction of the VB, the direction of movement of a VV and the longitudinal axis of the receiving volume of the PM have the same alignment / orientation in space, in particular are aligned with each other along a common straight line, so that preferably the longitudinal axis of a PM received by the PH lies aligned in the insertion direction of the plug and in the direction of movement of the closing device / setting tube.

[0039] In a further embodiment of a primary packaging holder (PH) according to the invention, the PH has at least one holding element and / or at least one alignment element and / or at least one combined holding and alignment element, wherein, in the case of at least two elements, a first alignment element (and / or a combined element) is preferably arranged below a first holding element (and / or below a combined element), wherein the first holding element (and / or the combined element) preferably comprises a first PKF, and in particular a second alignment element and / or holding element (and / or a combined element) is arranged below the first holding element (and / or below a combined element) and spaced apart along the positioning axis from the first element, wherein the PH is in particular configured to receive a PM in such a way thatthat in a state recorded by the PH, one or more contact surfaces of the PM are in contact with the at least one holding element and / or the at least one alignment element and / or the at least one combined element.

[0040] In a further embodiment of a PH according to the invention, the PM preferably rests with at least one of its contact surfaces on one of the existing elements. In other words, the PM rests with at least one contact surface on each element.

[0041] In a further embodiment of a primary packaging holder PH according to the invention, the PH has a contact surface extending downwards from the first HA and parallel to the first positioning axis, in particular a rib, which is configured to support or hold a received PM in the aligned position; in particular, the rib has an ACF as defined by the invention. In another possible embodiment, the contact surface of the rib extending parallel to the first positioning axis fulfills the function of an ACF and does not contribute to the technical function of holding or supporting, and thus does not have a PKF. In a further embodiment, the rib is designed (and in particular has one or more corresponding surfaces, e.g., on its upper side) such that it has both a PKF and an ACF as defined by the invention.This allows the bridge of the PH to align a PM, in particular a syringe, cartridge, or vial, in accordance with the invention and hold it in a predefined position (for example, by means of a PKF on its upper side, relative to a functional installation or use state of the PH). In a further embodiment, the bridge can have a further AKF / PKF, particularly on its lower edge facing the bottom of a PM. The contact surfaces of the PH, in particular an AKF and / or a PKF, have a particular roughness, preferably Ra 0.4 µm to less than or equal to Ra 0.8 µm, as described in more detail herein.

[0042] In a further embodiment of a PH according to the invention, the PH has a first HA and a second HA, wherein the web extends in particular between the at least first and at least second HA and the preferably web has defined dimensions, in particular a first height (see reference numeral H1 in Figs. 24a to 24d ) and a second height (see reference symbol H2, e.g. in Figs. 24a to 25aThe first height (H1) is, in particular, the height from the upper edge of the upper retaining arm (on which the PM rests with the first section of the contact surface) to the lower edge of the lower retaining arm. The second height (H2) is the height between the lower edge of the upper retaining arm and the upper edge of the lower retaining arm. The difference between the first height (H1) and the second height (H2), i.e., in particular H1-H2, yields the sum of the thicknesses of the retaining arms and thus (with appropriate design in some embodiments) the height or the longitudinal extent of the at least one alignment contact surface (ACF), which is in contact with, or can be brought into contact with, the lateral surface of the PM and the underside of the PM's edge according to the invention.The desired position and / or orientation of the PM within the PH can be predefined by the design of the PH, in particular its dimensions and the arrangement and orientation of the PKF and / or AKF (and thus also the first height and / or the second height and / or their ratio or difference to each other), and taking into account the dimensions of the PM to be accommodated (especially the length of the PM's receiving volume along its longitudinal axis (length = from the top edge of the first opening to an existing mark or to the outermost point of the inside of the receiving volume)). This allows the desired position and / or orientation of the VB within the receiving volume of the respective PM to be predefined. The position of the PKF along the positioning axis can be used to adjust, in particular, how deep or high, i.e.,The position of the filling element (ME) along the longitudinal axis of the PM's receiving volume is determined (depending on the (set) stroke of the flow control). The orientation of the filling element can be influenced by the alignment of the activated carbon filter (ACF), and in particular by its extent and / or the spacing of the individual sections parallel to the positioning axis of the pump (determined by the first height and / or the second height). This influences the orientation of the PM, especially the inclination of the longitudinal axis of the PM's receiving volume relative to the positioning axis of the pump, and thus, in a system-integrated state, the pump's orientation relative to a system axis. The predefined position of the filling element is based on the lowest point of the filling element, e.g., a plug, directed towards the surface (minicus) of the prefilled formulation containing a composition.Between the lowest point of the inserted plug and the lowest point of the surface (minicus) of the pre-filled formulation containing a composition—where the plug is held oriented along the positioning axis—a freely selectable distance is ensured by the inventive PH, arrangement, and sealing method. This distance can be, in particular, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 2 cm, 3 cm, 4 cm, and up to 15 cm (depending on the plug). Specifically, this distance between the plug (e.g., a stopper) and the formulation containing a pharmaceutical composition in a syringe is greater than or equal to 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 2 cm, 3 cm, 4 cm, and less than or equal to 5 cm. This position of the plug is ensured by appropriate parameter setting in the VV and thanks to the reproducible insertion of the plug at the predefined position in the receiving volume.In particular, the dimensions of the PH (preferably the first height and the second height - H1 and H2) are chosen such that, in the process of closing the PM, the VB, in particular the stopper, is inserted into the predefined position in the receiving volume of the PM, in particular the syringe. Specifically, the VB (in particular, for example, a stopper) is positioned in such a way that it does not come into contact with the prefilled formulation containing a composition, but rather is positioned at a defined distance from it in an area as described above within the receiving volume.

[0043] In a further embodiment of the PH according to the invention, the PH can be mounted on a guide rail (FS), in particular such that the PH in an installed state (on the FS in a (filling system)) can be aligned with its first positioning axis in a horizontal plane and relative to the first system axis, preferably to a longitudinal axis of the VB, relative to the insertion direction of a VB and / or relative to a movement direction (V) of a VV, in particular in alignment, and in particular can be fixed on the FS by means of at least one, preferably two, fastening means.

[0044] In a further embodiment of the PH according to the invention, this PH has at least one, preferably two, through-holes extending through the PH, which in particular extend parallel to the positioning axis of the PH, so that the PH can be aligned and / or mounted in and / or on the FS with one, preferably two, fastening means – in particular screws. The fastening means are preferably variable and can be designed with reference to the expert knowledge of a person skilled in the art. By means of the fastening means, which in particular extend through the through-holes and which, as already mentioned, can in particular be screws, the PH can be aligned on the FS in the horizontal plane and fixed on the guide rail.

[0045] In a further embodiment of the PH according to the invention, the PH has at least one, preferably two, through-holes extending through the PH, in particular as described above, wherein the through-holes extend in particular parallel to the positioning axis of the PH, wherein the at least one through-hole is in particular designed such that suitable fastening means - e.g. screws - for fastening the PH to an FS can be passed through the at least one through-hole - or both or the several - in particular to connect the PH in an arrangement with an FS, and wherein the PH, in particular in an arrangement, can be aligned and in particular fixed in and / or on the FS by means of the through-holes, in particular in conjunction with one, preferably with two, fastening means, in a state of the FS properly installed in a system, in particular relative to a first system axis.

[0046] In a further embodiment of the PH according to the invention, this PH has at least one, preferably two, through-holes extending through the PH, which extend in particular parallel to the positioning axis of the PH, wherein the through-holes are in particular designed such that suitable fastening means - e.g. screws - for fastening the PH to an FS can be passed through the through-holes, in particular to connect the PH in an arrangement with an FS, and wherein the PH, in particular in an arrangement, can be aligned and in particular fixed in and / or on the FS by means of the through-holes, in particular in conjunction with the suitable fastening means, in a state of the FS properly installed in a system, in particular relative to a first system axis.

[0047] In a properly installed state of the PH in a system, in particular in a properly installed state of an arrangement comprising a PH and an FS, the first positioning axis of the PH coincides with a first system axis in the system, in particular these are aligned with each other, wherein in particular the positioning axis of the PH coincides with the insertion direction of the VB and / or the direction of movement of the VV, in particular is aligned with this / these.

[0048] Another aspect of the present invention is an arrangement comprising a guide rail (FS), wherein the FS is designed for use in a filling plant and / or in a plant for (automated) sealing, preferably comprising a sealing device (200), of a PM and the FS is designed to accommodate at least one PH according to the invention, and at least one or more primary packaging holders according to the invention, wherein the FS is preferably designed to accommodate two or more PH, preferably to accommodate at least 3, 4, 5, 6, 7 or 8 or more primary packaging holders, and wherein the at least one PH can be mounted on the guide rail or is mounted, preferably with at least one, preferably with at least two fastening means, in particular with two screws.

[0049] In an advantageous embodiment, the PH and / or the FS are designed such that, in particular, the arrangement is such that the PH can be moved laterally (relative to a functional installation state of the PH and / or the arrangement in a system, e.g., along the x-axis of a system) and / or forwards / backwards (relative to a functional installation state of the PH and / or the arrangement in a system, e.g., along the y-axis of the system) on the guide rail. This allows the PM in the PH to be aligned via the position of the PH in the system, particularly in an xy-plane of the system and relative to the z-axis of the system (especially relative to the system axis). This, together with the alignment surfaces of the PH, and in particular together with the alignment surfaces of the retaining arms of a PH, affects the overall alignment.

[0050] In a further embodiment of an arrangement according to the invention, this further comprises at least one VV, preferably a VV comprising a setting tube, wherein the VV and the setting tube are arranged in particular above the at least one PH, preferably in a state of the arrangement installed in a system for (automated) closing of a primary packaging material, optionally at least one PM which is received by the at least one PH, wherein by means of the arrangement at least one PM, in particular syringe, cartridge or vial, with a predefined orientation and / or orientation in space can be received and in particular held at least temporarily, in particular for closing the PM, wherein the PM can in particular be held in a predefined position and / or with a defined orientation relative to a position of a VB to be inserted into the primary packaging material, in particular a stopper, along an insertion direction (E) of the VB and a movement direction (V) of the VV.

[0051] Another aspect of the present invention is a guide rail for receiving a PH in accordance with the invention and characterized in that the guide rail is designed for an arrangement according to the invention.

[0052] Another aspect of the present invention is the use of a PH or the arrangement according to the invention for holding a PM with a predefined orientation and / or orientation in space, in particular for holding a PM in a system for (automated) filling and closing the PM, preferably comprising a VV for (automated) closing a PM. The PH can be used in a filling system for food products, in a filling system for formulations containing a cosmetic composition, and / or particularly in a filling system for formulations containing a pharmaceutical composition.

[0053] The primary packaging holder or an arrangement with the primary packaging holder can be a component of a new system, or the primary packaging holder or an arrangement with the primary packaging holder can be retrofitted to existing systems.

[0054] Another aspect of the present invention is a method for aligning a PM in a system (in particular, for example, in a corresponding filling system), in particular in a system preferably comprising a VV for (automated) closing of a PM with a VB, wherein the PM has an outer surface (e.g., a lateral surface of the PM) and a receiving volume extending at least partially along a longitudinal axis with at least one first opening, wherein the first opening of the receiving volume of the PM can furthermore be closed, in particular by means of a VB, preferably a plug, which can be inserted or is inserted into the first opening along the longitudinal axis of the receiving volume, wherein a PH or an arrangement according to the invention is used for aligning the PM and the PM is aligned by means of the PH at a predefined position and with a predefined orientation.

[0055] In a further embodiment, a method for alignment comprises at least the following steps: Providing a system with a PH suitable for aligning and holding a PM according to the invention or with an arrangement according to the invention; inserting and aligning the PH in the system, in particular such that the first positioning axis coincides with the first system axis, with an insertion direction of the VB and the direction of movement (V) of the VV, or the PH is in particular inserted into the system and aligned in it such that the first positioning axis of the PH coincides with an insertion direction of the VB or direction of movement of the VV; providing a PM to be received, in particular a syringe, cartridge or vial; inserting the PM, preferably against a resistance, wherein the resistance results in particular from the properties of the closure component and the properties of the PM (in particular from the material properties and / or the dimensions of the components).into at least one receiving device of the PH for receiving the PM, wherein the at least receiving device preferably has a first HA with an outer surface, and optionally (if the PM has not already been aligned during insertion) alignment of the PM, wherein the alignment of the PM is carried out by inserting the PM into the PH or positioning it in the PH such that the PM (after alignment) is in contact with the first PKF of the PH with a first section of its outer surface and with the second section of its outer surface with the AKF of the PH, , where the PM is particularly aligned when the longitudinal axis of its receiving volume is aligned with the first system axis, in particular with the direction of movement (see e.g. reference numeral V in Fig. 1 ) of the system, preferably with the direction of movement (see e.g. reference numeral V in Fig. 1 ) the closure device. coincides, preferably aligns, and the closure component for closing the primary packaging can be inserted, in particular inserted, into the first opening of the primary packaging along the insertion direction.

[0056] Another aspect of the present invention is a method for closing a PM, wherein the primary packaging has an outer surface and a receiving volume extending at least partially along a longitudinal axis with at least one first opening, wherein the first opening of the receiving volume of the primary packaging can furthermore be closed, in particular by means of a closure component which can be inserted into the first opening for closing the primary packaging along the longitudinal axis of the receiving volume, wherein the primary packaging is preferably prefilled with a formulation containing a composition, comprising at least the steps: Providing a predefined position and / or orientation relative to a position of a closure component to be inserted into the primary packaging along an insertion direction of the closure component and along a movement direction of a sealing device for closing the primary packaging, preferably prefilled, in particular in a system (especially a filling system), wherein the sealing device is in particular part of the system, preferably oriented such that a longitudinal axis of the receiving volume of the primary packaging is aligned with the longitudinal axis of the closure component and / or the movement direction of the sealing device, and placing the closure component, in particular by means of a sealing device. wherein the primary packaging material is received during the setting of the closure component by a PH according to the invention or one of its embodiments, or by a PH that is part of an arrangement according to the invention.

[0057] In the inventive method for closing a PM, the closure component is placed, in particular, at a predefined position along the longitudinal axis of the receiving volume within the receiving volume of the primary packaging material, preferably with a defined air space between a formulation with which the PM may in particular be prefilled, and the VB, in particular its underside.

[0058] In one embodiment of the inventive method for closing a PM, the PM is held in space, particularly at a predefined position and / or with a predefined alignment and / or orientation, when placed by means of the PH or by means of the PH of the arrangement, particularly for closing the primary packaging material, wherein the primary packaging material is held in a predefined position and / or with a defined orientation relative to a position of a closure component (VB) to be inserted into the primary packaging material along an insertion direction of the closure component.

[0059] In further embodiments of the inventive method for closing a PM, one or more of the following steps (designated as "Option 1", "Option 2" and "Option 3") can optionally be carried out: Option 1: Aligning and positioning the PH in a system (in particular a filling system) such that, when properly installed, the PH's first positioning axis, the first system axis (and the direction of movement of the VV and the insertion direction of the VB) are aligned. Option 2: Aligning the PH, which can be mounted in an aligned manner, in particular on a guide rail, with its first positioning axis in a horizontal plane and relative to the first system axis, so that the first positioning axis and the insertion direction are aligned with the system axis. Option 3: Fixing (= securing in the desired position with the desired orientation) the PH arranged and aligned on a guide rail in the system, in particular by means of at least one, preferably two, fastening means on the guide rail.so that the PH, when properly installed in the system, is fixed with its first positioning axis in an insertion direction of the VV and, in particular, is held in this position and orientation during the insertion of the VB.

[0060] Each of the optional steps "Option 1", "Option 2", "Option 3" can be carried out alone or in any combination with an embodiment of the method according to the invention.

[0061] In a further embodiment of a method for closing a PM according to the present invention, wherein the PM has an outer surface (in particular a lateral surface of the PM, especially in the case of a syringe, cartridge or vial) and a receiving volume extending at least partially along a longitudinal axis with at least one first opening, wherein the first opening of the receiving volume of the PM can furthermore be closed, in particular by means of a VB, in particular a stopper, wherein the VB can be inserted into the first opening for closing the PM along the longitudinal axis of the receiving volume, wherein the PM is preferably prefilled with a formulation containing a composition, the method comprises the following steps: Providing a prefilled PM, preferably prefilled, in a predefined position and / or with a defined orientation relative to a position of a VB to be inserted into the PM along an insertion direction of the VB and along a movement direction of a VV for closing the primary packaging material, particularly in a system (especially in a filling system), preferably oriented such that a longitudinal axis of the receiving volume of the PM is aligned with the longitudinal axis of the VB and / or the movement direction of the VV of the system, optionally aligning and positioning the PH in such a defined way in the system that, in a properly installed state of the PH in the system, the first positioning axis of the PH and the first system axis (and in particular the movement direction of the VV and the insertion direction of the VB) are aligned with each other.Optionally, aligning the PH, which can be mounted in a guide rail, with its first positioning axis in a horizontal plane of the system and relative to the first system axis, so that the first positioning axis and the insertion direction are aligned with the system axis; optionally, fixing the PH arranged and aligned on a guide rail in the system, in particular by means of at least one, preferably two, fastening means on the guide rail, so that the PH is fixed in an installed state with its first positioning axis in an insertion direction of the VV, in particular so that the PH is held in this position during the setting of the VB; and setting the VB, in particular by means of a VV. wherein the VV preferably comprises a setting tube, wherein the VB is placed in particular at a predefined position along the longitudinal axis of the receiving volume within the receiving volume of the PM, and wherein the PM is held in particular by means of an arrangement according to the invention with a predefined alignment and / or orientation in space, particularly when closing the PM, wherein the PM is in particular in a predefined position and / or with a defined alignment relative to a position of a VB to be inserted into the PM along an insertion direction of the closing direction.

[0062] In a further embodiment of a method according to the invention for closing a PM, the insertion (synonymous with "insertion") of the VB preferably takes place under vacuum, in particular the insertion of a stopper, especially with the aid of a vacuum chamber, particularly if the PM is a syringe body (synonymous with "syringe") or a cartridge, preferably a pre-filled syringe body or a pre-filled cartridge.

[0063] In a further embodiment of a method according to the invention for closing a PM, the VB is inserted, in particular in an insertion direction along a direction of movement of the VV and aligned with the first positioning axis of the PH, in particular such that, especially if the PM is a syringe body or cartridge, the VB is located at a predefined position in the receiving volume of the PM after insertion, i.e. within the receiving volume at a defined position, and closes the PM, in particular properly.

[0064] In a further embodiment of a method according to the invention for closing a PM, the VB is placed at a predefined position in the receiving volume of the primary packaging material such that, after insertion at a predefined position, it is located above a formulation containing a composition filled into the PM, in particular above a liquid formulation containing a pharmaceutical composition, wherein the VB, in particular a stopper, is preferably inserted into the PM in such a way that it does not come into contact with the prefilled formulation containing a composition at the predefined position and in particular a predefined air space is formed between the prefilled formulation containing a composition and the inserted VB.

[0065] In a further embodiment of the method, the PM is a syringe body, preferably a pre-filled syringe, more preferably a 0.5 ml Plajex™< Terumo®< syringe, and the VB is a stopper, wherein the syringe is properly aligned and held in an inventive PH, preferably in an inventive arrangement, so that by means of a VV the stopper is inserted into a predefined position along the longitudinal axis of the receiving volume of the syringe. Definitions

[0066] A Primary packaging(PM) within the meaning of the invention is a container made of plastic or glass with a receiving volume. The inner surface of the container facing the receiving volume can have a coating with a desired function, such as a silicone-based coating or another coating, or several or a combination thereof, known from the prior art. A primary packaging material within the meaning of the invention is suitable for use in the pharmaceutical, cosmetic, and food industries, or is intended and suitable for filling / receiving formulations containing a pharmaceutical composition, formulations containing a cosmetic composition, and / or foodstuffs. The respective geometry of the receiving volume and the external geometry are determined by the application area, which is known to those skilled in the respective industry.The formulations that can be filled into such a primary packaging material, containing a composition, are in particular liquids with a variable viscosity, solids, gaseous, or a solid / liquid mixture with a variable viscosity. The holding volume of such a primary packaging material is typically in the range of 0.2 ml to 5 L. The holding volume of a primary packaging material for use with formulations containing a pharmaceutical composition is in particular greater than or equal to 0.05 ml up to 500 ml, 0.2 ml up to 200 ml, 0.2 ml, 0.5 ml, 1 ml, 1.5 ml, 2 ml, 2.5 ml, 3 ml, 5 ml, 10 ml, 15 ml, 20 ml, 25 ml, 30 ml, 40 ml, 50 ml, 100 ml, 150 ml, 200 ml, 250 ml, 500 ml, up to 1000 ml.

[0067] The holding volume of the PM (provisional container) must be distinguished from the filling volume of the formulation intended for filling. The holding volume of a PM is determined by the scale printed on the PM (e.g., syringe) or by the data sheet available for the respective PM, which specifies the holding volume for that particular PM. The filling volume of the formulation intended for filling is freely selectable within the holding volume of the PM and depends on the specifications of the intended application and use of the formulation containing a desired composition in the pre-filled PM. The filling volume is therefore less than or equal to the holding volume.The filling volume is preferably greater than or equal to 0.05 ml, 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.5 ml, 1 ml, 1.5 ml, 2 ml, 2.5 ml, 3 ml, 5 ml, 10 ml, 15 ml, 20 ml, 25 ml, 30 ml, 40 ml, 50 ml, 100 ml, 150 ml, 200 ml, 250 ml, 500 ml and any volume in the range greater than or equal to 0.05 ml to less than or equal to 1000 ml.

[0068] Examples of primary packaging materials (PM) for which the PH described herein according to the present invention is generally suitable include: Possible plastics or polymers from which the PM may be made, comprising cyclic olefin polymer (COP), polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET, PETE), polytetrafluoroethylene (PTFE), polystyrene (PS), polycarbonate (PC), polymethyl methacrylate (acrylic, PMMA), polymethylpentene (PMP), polyvinyl chloride (PVC), and mixtures of at least two of the aforementioned polymers or combinations thereof (e.g., different layers). Possible glasses from which the PM may be made include borosilicate glass, soda-lime glass, quartz glass, and mixtures of different glass materials. Glass materials for PM include differently manufactured and differently shaped glass. PM as defined herein also encompasses pharmaceutical glass bottles. These include shaped glass bottles and tubular glass bottles.Molded glass bottles are produced by shaping molten glass in a mold, creating a bottle with a specific shape and design. Tubular glass bottles are made from glass tubes that are heated and blown into a bottle shape. Molded glass bottles are available in a wider variety of shapes and designs. Tubular glass bottles are typically cylindrical or rectangular and are thinner and lighter than molded glass bottles. However, tubular glass bottles are less prone to breakage than molded glass bottles. Various glass grades, such as Exp 33 or Exp 51, or coated glasses (e.g., with a polymer, silicone resin, or silicone derivative) are also glass materials used for PM (permanent metal products).

[0069] The plastic or glass can be transparent or colored. Each of the aforementioned materials from which the PM can be manufactured can be used alone or in combination with at least one of the others. Each of the aforementioned materials from which the PM can be manufactured can have a coating, in particular a silicone coating. Potential suppliers and manufacturers of PM are described herein.

[0070] One embodiment of primary packaging materials according to the invention comprises syringe bodies, syringes, and prefillable syringes or prefillable syringe bodies, each made of plastic or glass. Volumes can range from 0.05 ml to 100 ml, 0.5 ml to 500 ml, 1 ml, 2 ml, 2.5 ml, 3 ml, 5 ml, 10 ml, 20 ml, 30 ml, 40 ml, 50 ml, and any other volume. Specific examples include the 3-part Plajex™< Terumo syringe from Terumo, available with or without a Luer lock, and the prefillable syringes from Terumo under the brand name Plajex™< Ready-to-Fill Polymer Syringe, available with or without a Luer lock and with or without a silicone coating. The general specifications of the Plajex™< syringes are shown here: specification Description Syringe body material Cyclo Olefin Polymer (COP) syringe size 0.5 ml, 1 ml long, 2.25 ml According to ISO 11040-6 Lubrication of syringe body silicone oil Optional: 0.5 ml, 1 ml long silicone oil-free Luer lock Integrated Luer lock compliant with EN-ISO 80369-7 Twist-off tip cap Chlorobutyl rubber (CIIR) - Rubber part - Rigid component Polypropylen Flange shape Cut flange According to ISO 11040-6 Plug Chlorobutyl rubber (CIIR) according to ISO 11040-5 Optional: 0.5 ml, 1 ml long i-coating™ (silicone resin coating)

[0071] The syringe bodies or syringes comprise an upper rim (flange), also referred to as a wing. The rim can be arranged uniformly around the upper opening or only partially. The upper rim is therefore not necessarily uniform over the entire radius. The rim is shaped such that a sufficient contact surface with the primary packaging holder is provided in accordance with the invention. A rim can be designed in the form of wings.

[0072] Another embodiment of primary packaging materials according to the invention comprises all common vials. These include vials, in particular vials from the aforementioned suppliers Becton Dickinson (BD), Gerresheimer, Stevenato, and Schott, e.g., BioPearl™ Microspheres Resorbable drug-eluting microspheres and QuiremSpheres™ Microspheres from Terumo, as well as cartridQ YpsoDose. A further embodiment of primary packaging materials according to the invention comprises all common cartridges, which also have an upper rim. Examples of cartridges are those used in delivery systems and injection systems (e.g., disclosed in EP4243895A1, EP3490643B1) and which are known, for example, under the brand names SmartDose® and SmartDose® Delivery System 10 On-Body Delivery System (West Pharma).

[0073] One embodiment of primary packaging materials according to the invention comprises all common cartridges or cylindrical ampoules. The group of cartridges includes single-chamber and double-chamber cartridges, cartridges with a volume of 1 to 20 ml, volumes of 0.6-1.5 ml, 1.5 ml, 1.6 ml, 1.8-2.2 ml, 3.0 ml, 3.0-5.0 ml, 3.0-10.0 ml, and 20 ml, cartridges made of plastic (e.g., COP), cartridges made of a glass material, and cartridges made of the container material FIOLAX® or DURAN® (expansion coefficients 33 or 52), which is a clear type I borosilicate glass. Cartridges from SCHOTT (e.g. CartriQ) or OMPI or Stevenato Group (e.g. Nexa ®< , EZ-fill ®< , Nexa ®< 3X EZ-fill ®< ) are particularly preferred.

[0074] The PM – regardless of the material it is made of – can have at least a partial external surface coating on its outer surface. Silicone coatings are an example of external surface coatings. This coating can result in a particularly smooth and low-friction surface, especially in cartridges.

[0075] A edgeA PM according to the invention has an edge that at least partially surrounds the first opening of the PM, and in particular projects outwards. The edge has, in particular, an underside extending in one direction, in particular a plane, perpendicular to the longitudinal axis of the receiving volume. The edge can radially surround the first opening of the PM at least partially or even completely. This underside of the edge is preferably designed such that it provides a sufficient surface area with which the PM can be received in the PH, preferably with its underside resting on the PKF, in particular on the PKF of a first, in particular upper, HA, whereby the PM is brought into contact with at least one PKF and / or AKF. The underside of the projecting edge of the PM – e.g.a flange / wing of a syringe - in particular forms the first section of the outer surface of the PM, with which the first PKF can / will be brought into contact for / at the defined positioning of the PM in the PH.

[0076] In syringes, the edge can be defined, for example, by the flange or so-called wing (see e.g. Fig. 14b, f, g ) be formed. The bearing surface of the wing intended for reception in the PH is formed on the underside of the edge, in particular perpendicular to the longitudinal axis of the receiving volume, in order to ensure proper reception of the PM in the PH, preferably in an HA, in particular an upper HA, of the PH.

[0077] Thus, a first section of the outer surface is formed, in particular, by the underside of the full-circumference flange or partially circumferential rim in the form of wings of the syringe, or the underside of a rim of a vial or cartridge, and the second section of the outer surface is formed, in particular, by at least a section of the outer surface of a syringe, cartridge, or vial. In the case of cartridges, the rim is also called a crimped rim and is likewise suitable as a rim within the meaning of the invention, which corresponds to a first section of the outer surface of the PM.

[0078] A Closure component(VB) within the meaning of the invention comprises bodies in three dimensions which are suitable for sealing a PM within the meaning of the invention – as defined herein. VBe within the meaning of the invention are designed such that they have a region which has an outer geometry relative to the geometry of the receiving volume of the PM, such that the VB can seal the PM by being inserted into the PM, wherein the VB can be positioned at a predefined position within the receiving volume of the PM. The part of the VB that is inserted into the PM along the longitudinal axis of the receiving volume can be conical. In one embodiment, at least one region of the VB, in particular the region of the VB to be inserted into the receiving volume of the PM, is at least partially compressible, so that it can be inserted into the receiving volume of the PM, in particular under vacuum, by applying a force against a defined resistance.The VB can have a further area that covers the first opening of the PM's receiving volume. In another embodiment, the VB has an area that can be inserted into the PM's receiving volume and an area that covers the opening of the PM's receiving volume.

[0079] In another embodiment of the VB, no compression of the VB is required to insert it into the receiving volume. The proper sterile closure of the first opening of the PM, and thus a sterile seal of the PM, is ensured by the precise geometry of the VB in relation to the corresponding PM. In a further embodiment, the VB, which is particularly non-compressible, is held in the receiving volume by a form-fitting manner, particularly by a vacuum, thus ensuring a sterile seal.

[0080] The VB can be made of silicone, ethylene propylene diene monomer (EPDM) rubber, acrylonitrile butadiene rubber (NBR), polyethylene (PE), natural rubber (NR), thermoplastic rubber (TPG), PVC-P, polytetrafluoroethylene (PTFE), bromobutyl, chlorobutyl, vinyl, cork, glass, or a mixture or combination of the aforementioned materials, and / or be at least partially coated with one of the aforementioned materials. In one embodiment, the VB has, in particular, at least a partial silicone coating. In another embodiment, the VB is made of a chlorinated isoprene-isobutene or chlorobutyl and is additionally coated with a silicone resin. Such VBs are particularly suitable for use in syringes, such as Terumo syringes (preferably the 0.5 ml Plajex™ Terumo syringe).

[0081] VBe includes all common stoppers and replaceable stoppers made of elastic material. Stoppers include lamellar stoppers, stoppers with external hooks, stoppers with an inner rod, stoppers with hooks and an inner rod, rolled-edge stoppers, injection stoppers, push-in stoppers, and screw-in stoppers, each with or without a Luer lock. Further VBe include sealing caps, sealing caps, overcaps, combination stoppers, and combi-stopper closure cones, each with or without a Luer lock. VBe suitable for syringes and VB suitable for cartridges and vials are also included. Preferably, a VB according to the invention can be inserted under vacuum into the receiving volume of the desired PM.

[0082] A predefined airspace defines a volume or space between the lowest sealing surface of the VB (e.g., the lip of the plug, as in Fig. 4shown) and the lowest point of the surface (minicus) of the prefilled formulation containing a composition. A predefined air space can be specified as a volume, e.g., in ml, or as a freely selectable distance between the lowest sealing surface of the VB (e.g., the lip of the stopper, as shown) and the lowest point of the surface (minicus) of the prefilled formulation containing a composition. Fig. 4 (shown) and the lowest point of the surface (minicus) of the pre-filled formulation containing a composition – the PM being held oriented along the positioning axis. This distance to the stopper can be at least partially equal to 0, and thus the stopper can be in contact with the formulation containing a composition ("touching liquid"). Air space does not necessarily imply that the space defined above must be filled with air or any other gas. The air space can be a volume / space resulting from the method of sealing the PM under vacuum.

[0083] The depth to which the stopper protrudes into the formulation containing a composition depends on the requirements of the product and process and is freely selectable. The distance can be greater than or equal to 1 mm, greater than or equal to 2 mm, greater than or equal to 3 mm, greater than or equal to 4 mm, greater than or equal to 5 mm, greater than or equal to 6 mm, greater than or equal to 7 mm, greater than or equal to 8 mm, greater than or equal to 9 mm, greater than or equal to 10 mm, greater than or equal to 2 cm, greater than or equal to 3 cm, greater than or equal to 4 cm, and any distance within a range that is technically feasible in the holding volume of the respective PM. In one embodiment, the distance between the stopper and the formulation containing a pharmaceutical composition in a syringe is 0 mm, greater than or equal to 1 mm, greater than or equal to 2 mm, greater than or equal to 3 mm, greater than or equal to 4 mm, greater than or equal to 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 2 cm, 3 cm, 4 cm, down to less than or equal to 5 cm.

[0084] With the PH described here, many positions of the VB are possible – depending on the application (with and without vacuum (i.e., compressible and non-compressible stopper placement), from bubble-free (absolute absence of air space) to precisely positioned distance of the stopper (= predefined air space). From a technical perspective, there are no limiting parameters that would restrict a preferred air space between the stopper and the formulation containing a composition.

[0085] A PM within the meaning of the invention is in a properly received state by the PH when the PM is in contact with the at least one first PKF with at least a first section of its outer surface (e.g., with an underside of the flange of a syringe) and simultaneously with at least a second section of its outer surface (e.g., a section of an outer shell surface of a syringe) is in contact with the at least one AKF. This means that all involved z-axes or longitudinal axes, which extend in the vertical direction with respect to the sealing process, are aligned with each other during the method of sealing the PM (e.g., plug insertion), particularly in a state of the PH functionally installed in a system with a PM received therein (e.g., in the case of a syringe), so that the sealing component (VB) (e.g.,(a plug) is "properly" aligned with its longitudinal axis in the insertion direction and along the direction of movement of the closure device (e.g., setting tube / plunger) in the longitudinal axis of the PM. This definition applies to all aspects and embodiments of the present invention.

[0086] The first positioning axis of the PH, when properly installed in a system, aligns with the first system axis of the system if these axes (i.e., the first positioning axis of the PH and the system axis) coincide, i.e., run along a common straight line or are not more than + / - 0.05 mm to 1.0 mm eccentric / laterally offset to this and an inclination of the first position axis of no more than + / - less than or equal to 3° to 0° from the insertion direction

[0087] Preferably escapesThe first positioning axis of the PH coincides with the first system axis when these axes coincide, i.e., running along a common straight line, or differs by no more than + / - 0.05 mm, + / - 0.06 mm, + / - 0.07 mm, + / - 0.08 mm, + / - 0.09 mm, + / - 0.10 mm, + / - 0.11 mm, + / - 0.12 mm, + / - 0.13 mm, + / - 0.14 mm, + / - 0.15 mm, + / - 0.2 mm, + / - 0.3 mm, + / - 0.4 mm, + / - 0.5 mm, + / - 0.6 mm, + / - 0.7 mm, + / - 0.8 mm, + / - 0.9 mm, + / - 1.0 mm; preferably the range of less than or equal to + / - 1.0 mm, more preferably less than or equal to + / - 0.5 mm, particularly preferably less than or equal to + / - 0.05 mm eccentrically / laterally offset to this and an inclination of the first position axis by no more than less than or equal to + / - 3°, + / - 2.5°, + / - 2°, + / - 1.5°, + / - 1°, + / - 0.5°, preferably + / - 0.1°, very preferably + / - 0.05° preferably less than or equal to 3° from the insertion direction.

[0088] One AttachmentAccording to the invention, a system, preferably operable in an aseptic or sterile environment, is designed and, in particular, configured to carry out all process steps for the production of a filled PM according to the invention. For this purpose, the system comprises at least one closure device according to the invention for (automatically) closing the PM and, preferably, for (automatically) inserting a stopper into the PM according to the invention. The system can be a system for filling formulations containing a pharmaceutical composition, a system for filling formulations containing a cosmetic composition, or a system for filling food products – each as defined herein.

[0089] Packaging machines and filling systems of this kind for liquid, pasty, and powdery formulations containing a composition are offered, for example, by OPTIMA GmbH, Bausch+Ströbel SE + Co. KG, Bausch Advanced Technologies, VisoTec GmbH, Syntegon Technology GmbH (formerly Robert Bosch GmbH), Groninger Holding GmbH & Co. KG, IMA, BREITNER Abfüllanlagen GmbH, and Rommelag SE & Co. KG, among others. The PH (protection) according to the invention is suitable for arrangements in such packaging machines and filling systems from the aforementioned manufacturers and can be adapted to the respective technical requirements.

[0090] One Locking device (W)The device is a means of inserting / placing the VB (as defined herein) into / onto a PM (permanent device) or of sealing a PM with the aid of a VB. In one embodiment of the device, it comprises at least one insertion tube and a plunger, which are designed to insert a suitable stopper into a PM, in particular a stopper into a syringe. Another embodiment of the device is designed to insert / placing a VB suitable for cartridges into / onto the cartridge or to seal the cartridge. Another embodiment of the device is designed to insert / placing a VB suitable for cartridges into / onto the cartridge or to seal the cartridge. Another embodiment of the device is designed to insert / placing a VB suitable for a vial into / onto the vial or to seal the vial.

[0091] Pharmaceutical compositionsFrom a regulatory perspective, pharmaceutical compositions encompass both medicinal products and medical devices. Therefore, pharmaceutical compositions are sterile and must be filled and sealed under sterile conditions. They include liquid compositions of varying viscosities, such as therapeutic compositions containing biologics (e.g., antibodies, antibody fragments, viral therapeutics, viral vectors, oligonucleotides such as RNA or cell therapeutics), vaccine compositions (e.g., against COVID-19 or influenza), live attenuated vaccines, MMR combination vaccines, subunit vaccines, recombinant, polysaccharide and conjugate vaccines (e.g., HPV vaccines, mRNA vaccines), peptides or peptide conjugates, antibody-drug conjugates, other bioconjugates, tinctures of plant extracts, and medical devices in liquid or gel form.

[0092] Pharmaceutical compositionsThese include therapeutic and diagnostic compositions, which encompass so-called biologics and new drug modalities. Antibodies for use in in vivo diagnostics include arcitumomab, altumomab, igovomab, satumomab, sulesomab, and votumumab. Therapeutic antibodies include monoclonal antibodies, antibody-drug conjucates (ADC), bispecific antibodies, abciximab, aducanumab, adalimumab, alemtuzumab, anifrolumab, atezolizumab, avelumab, basiliximab, benralizumab, bevacizumab, bimekizumab, brolucizumab, canakinumab, caplacizumab, catumaxomab, Claudiximab, Cemplimab, Cetuximab, Daclizumab, Daratumumab, Denosumab, Dostarlimab, Dupilumab, Durvalumab, Eculizumab, Efalizumab, Emicizumab, Enlimomab, Epratuzumab, Evolocumab, Fremanezumab, Galiximab, Gemtuzumab-Ozogamicin, Golimumab, Guselkumab, ibritumomab-tiuxetan, idarucizumab, Inebilizumab, Infliximab, Ipilimumab, Isatuximab, Lanadelumab, Ligelizumab, Lumiliximab, Mepolizumab, Muromonab-CD3, Motavizumab, Natalizumab,Nirsevimab, Nivolumab, Obinutuzumab, Ocrelizumab, Ofatumumab, Omalizumab, Oregovomab, Palivizumab, Panitumumab, Pembrolizumab, Pertuzumab, Ranibizumab, Ramucirumab, Ravulizumab, Reslizumab, Rituximab, Risankizumab, Romosozumab, Satralizumab, Spartalizumab, Sutimlimab, telimomab, teprotumumab, tezepelumab, tildrakizumab, tislelizumab, tocilizumab, tositumomab, trastuzumab, ustekinumab, zanolimumab and more. In addition to the aforementioned antibodies and their fragments, pharmaceutical compositions also include therapeutic proteins and polypeptides, peptides, therapeutic peptides (e.g., GLP-1), cell therapies (e.g., CAR-T cells, stem cells, TCRT CAR-NK, Tlls), gene therapies (e.g., CRISPR / Cas systems), nucleic acid-based products (DNA and RNA molecules, RNAi, siRNA, and mRNA molecules), virus-based products (AAV, oncolytic viruses), and microbiome products.

[0093] Cosmetic compositionsinclude liquid compositions of varying viscosities, such as lotions, creams, hydrogels, gels, tinctures and any other cosmetic product.

[0094] Groceries also include Dietary supplement Such as immune system-supporting and stabilizing compositions. These include vitamin preparations, probiotics, and microbiome products, which, depending on their compositional properties (e.g., concentration) and national regulations (medicines, medical devices, food supplements), are classified as either pharmaceutical compositions or food supplements. Foods include sauces of all kinds, ketchup, mayonnaise, oils, vinegar, alcoholic beverages, spirits, wine, beer, and non-alcoholic beverages.

[0095] In terms of composition, the formulationThe formulation of any of the compositions described herein may be liquid, gel-like, or pasty, and may be of a desired viscosity, solid, powdery, or have a variable moisture content. It may also be any formulation that technically permits filling into a desired PM (pharmaceutical product). The viscosity may be within any technically fillable range and depends on the design of the filling equipment. A viscosity in the range (at 25°C) greater than or equal to 0.05 cP, preferably greater than or equal to 0.5 cP, greater than or equal to 1.0 cP to less than or equal to 2000 cP, less than or equal to 1500 cP, less than or equal to 500 cP, less than or equal to 100 cP, less than or equal to 50 cP, less than or equal to 20 cP, less than or equal to 10 cP, preferably in the range of greater than or equal to 0.05 cP to less than or equal to 10 cP, is preferred for formulations containing a pharmaceutical composition.Other embodiments of formulations of any of the compositions described herein may have viscosities ranging from 50,000 cP to 500,000 cP. The viscosity of a formulation is freely selectable after application of the composition.

[0096] The features, advantageous embodiments, and benefits presented with reference to the primary packaging holder PH apply, where technically feasible, not only to the primary packaging holder but also, correspondingly, to an arrangement and methods according to the invention, and vice versa, even if, to avoid repetition, they are described only in connection with one of these aspects. That is, one or more features, functions, or advantages described only in connection with a PH may also be part of an arrangement and / or characterize one of the methods described according to the present invention, provided this is technically feasible. Further features of the invention will become apparent from the claims, the figures, and the figure description.All features, feature combinations and definitions mentioned above in the description, as well as the features and feature combinations mentioned below in the figure description and / or shown in the figures alone, can be used not only in the combination specified, but also in other combinations or on their own.

[0097] The invention will now be explained in more detail with reference to the accompanying drawings, using several exemplary embodiments, particularly preferred ones, which are shown only schematically to illustrate the functionality and are generally not drawn to scale, wherein components or sections with the same or similar function may have the same reference numerals for the sake of easier understanding, even if they differ in their design. Brief description of the characters

[0098] They show: Fig. 1 :In principle, an exemplary embodiment of a section of a system with a locking device for (automated) locking of a PM with a VB, Fig. 2 : Examples of sealed PMn, here syringes sealed with a VB, here stoppers, Fig. 3 : In principle, this is an example of a PM sealed with a closure component, where the PM in this case is a syringe pre-filled with a composition and the VB is a stopper. Fig. 4a-f: Exemplary single and detailed views of filled, sealed syringes with different positions of the stopper in the syringe's receiving volume, some stoppers being properly inserted and others defective. Fig. 5 :in a perspective view from an oblique angle above a section of an embodiment of a PH according to the invention with a PM included therein during the closing process (here PM=syringe; VB=stopper), Fig. 6 : the pH from Fig. 5 in a different perspective representation and without a recorded PM, Fig. 7 : the PH from the Fig. 5 and 6 in another perspective view without a recorded PM, Figs. 8-10 : different views of PH from the Figs. 5-7 or of assemblies and individual parts of this PH, Fig. 11 : a side view of the PH from the Fig. 5-10 in a state installed in a system with a locking device, with a PM held by the PH facing the upper holding arm during a locking process, Fig. 12 : a perspective view of the PH from Fig. 11 with the PM before the closing process, whereby the PM is pre-filled, Fig. 13 : a first embodiment of an arrangement according to the invention with a guide rail and an embodiment of a PH according to the invention, in this case with the PH from the Fig. 5-12 , Fig. 14a-14g : various designs of PMn in accordance with the invention, Fig. 15 : An embodiment of an arrangement according to the invention in a state installed in a system, here a filling system, comprising a guide rail and a PH, which, as in the Fig. 5-13 is designed, wherein the system includes a closure device and the illustration shows the PH with a recorded PM, Fig. 16 : a different perspective on the PH from Fig. 15 in the system, but without the locking device, but with a gripping device for positioning a PM in the PH, Fig. 17 :The PH from the previous figures in a calibration device with a PM gauge for setting the PH as such for a positionally accurate recording of an associated PM, Fig. 18 : a section of a further embodiment of an arrangement according to the invention with a further embodiment of a guide rail and a further embodiment of a PH according to the present invention in a perspective view from an oblique angle above, Fig. 19 : a view from below of a section of the arrangement Fig. 18 , Fig. 20 : a perspective view of the underside of the arrangement from the Fig. 18 und 19 , Fig. 21 : a perspective view of a section of the guide rail from the arrangement from the Fig. 18-20 in individual part representation, Fig. 22 : a different perspective view of the guide rail from the Fig. 18-21 in individual part representation, wherein the guide rail is designed to accommodate 3 PHs, Fig. 23 : Exemplary fastening devices for attaching a PH to a guide rail, for example for attaching the PH from the Fig. 18-20 on the guide rail from the Fig. 18-22 , Fig. 24a : the pH from Fig. 18 in perspective view in detail representation, Fig. 24b : a further embodiment of a PH according to the present invention, Fig. 24c : a further embodiment of a PH according to the present invention, Fig. 24d : a further embodiment of a PH according to the present invention, Fig. 25a : a further embodiment of a PH according to the present invention, Fig. 25b : a further embodiment of a PH according to the present invention, Fig. 26 :a different perspective on the PH from Fig. 15 and 16 in the system, but without the locking device, but with a gripping device for positioning a PM in the PH as well as with a calibration gauge for aligning / calibrating the PH within the system, Fig. 27 : a different perspective on PH Fig. 26 during alignment using the calibration gauge in the system, Fig. 28 : a perspective view obliquely from the side of the PH from the Fig. 15-16 and 26-27 in a state aligned in the system with a PM taken up by the PH during the closing process, Fig. 29 : a flowchart for an embodiment of a method according to the invention for a schematic and exemplary explanation of the individual process steps, Fig. 30 :in a perspective view from an oblique angle above a section of a further embodiment of an arrangement according to the invention with a further embodiment of a guide rail with four embodiments of PHs mounted on the guide rail according to the present invention, Fig. 31 : in a perspective view from an oblique angle above a section of a further embodiment of an arrangement according to the invention with a further embodiment of a guide rail, in this case with eight embodiments of PHs mounted on the guide rail according to the present invention, Fig. 32 : in a perspective view from an oblique angle above a section of a further embodiment of an arrangement according to the invention with a further embodiment of a guide rail and a further embodiment of a PH according to the present invention, Fig. 33 :the arrangement from Fig. 31 in a perspective view from a low angle looking at the underside of the arrangement, Fig. 34 : In a perspective view from an oblique angle above, a section of a further embodiment of an arrangement according to the invention with the guide rail from the Fig. 30-33 , but with a further embodiment of a PH according to the present invention, and Fig. 35 : In a perspective view from an oblique angle above, a section of a further embodiment of an arrangement according to the invention with the guide rail from the Fig. 30-34 , the PHs from Fig. 34 as well as further embodiments of a PH according to the present invention. Detaillierte Beschreibung der Ausführungsbeispiele

[0099] Fig. 1 Figure 1 shows a schematic representation of an embodiment of a section of a system 1000 with a closure device 200 for (automatically) closing a primary packaging material 20 with a closure component 30. In this case, the primary packaging material 20 is a syringe 20 prefilled with a formulation containing a pharmaceutical composition 27 and is to be closed by means of a stopper 30 as the closure component 30. Accordingly, in this embodiment, the closure device 200 is specifically designed for stopper insertion and can therefore also be referred to as a stopper insertion device 200.

[0100] The primary packaging material 20, i.e., in this case the syringe 20, has a receiving volume 23 extending along a longitudinal axis L, into which the formulation containing a pharmaceutical composition 27 is introduced, in particular a defined quantity of the formulation 27, such that a defined fill level of the formulation 27 is established within the receiving volume 23. The receiving volume 23, as shown in the illustration in Fig. 1 , at its upper end a first opening 21 and a second opening at its lower end, not specified here, through which the formulation 27 can be dispensed during use, for example by means of an injection needle or the like, which can be connected to the syringe 20.

[0101] To close the syringe 20, the closure component 30, here the stopper 30, can be inserted into the receiving volume 23 of the syringe 20 in the direction of the longitudinal axis L of the receiving volume 23 via the first opening 21 by means of the closure device 200, in particular by means of an insertion piston 11, in such a way that the stopper 30 is subsequently located at least partially, preferably completely, within the receiving volume 23 and seals the primary packaging material 20 tightly upwards towards the opening 21.Preferably, the stopper 30 can be inserted into the syringe 20 in such a way that, after insertion, it is located at a defined position above the formulation containing a pharmaceutical composition 27 within the receiving volume 23 at a defined distance to a surface of the formulation containing a pharmaceutical composition 27 (not specified here), such that a gap is formed between a bottom surface of the closure component 30 and the surface of the formulation containing a pharmaceutical composition 27. Fig. 1 also an unspecified room (see room 40 in Fig. 3 ) with a defined volume.

[0102] To insert the closure component 30, in this exemplary system 1000, the setting piston 11 can be moved along a direction of movement V, which in this case also defines a first system axis A, like a punch towards the primary packaging material 20 and partially into it, as shown in the illustration in Fig. 1 especially downwards. This allows the closure component 30, here the stopper 30, to be moved along an insertion direction E and pushed, in particular pressed, into the syringe 20 until the closure component 30 is located in the desired position in the receiving volume 23 of the primary packaging material 20.

[0103] For a particularly advantageous sealing of the primary packaging material 20, the system 1000 further comprises a vacuum device, not specified in detail here, with a vacuum chamber 12, a setting tube 13 and a sealing device 14, as well as various other components, such as in particular at least one hose 15, several valves (in particular at least two shut-off valves 16 and 17) and at least one vacuum pump 19 and a manometer 18, for generating a negative pressure or a vacuum in the receiving volume 23 of the primary packaging material 20 during or before the insertion of the closure component 30 into the receiving volume 23.

[0104] The insertion tube 13 comprises a flange-shaped section 13A, with which the insertion tube 13 rests on a top surface of the vacuum chamber 12, and a tubular section 13B, which extends vertically through the vacuum chamber 12 and is connected to the hose 15 via a channel in the vacuum chamber (not otherwise specified). The insertion tube 13, and in particular the tubular section 13B, serves primarily to guide the closure component 30 during insertion into the primary packaging 20. The insertion tube 13, which is interchangeable, allows the vacuum device to be easily adapted to different closure components 30, especially closure components 30 with different outer diameters.

[0105] The sealing device 14, which is arranged below the vacuum chamber 12, serves to seal between the underside of the vacuum chamber 12 and an upper surface of the primary packaging 20 or its receiving volume 23, whereby the sealing device 14 can, in particular, compensate for a gap between the upper surface of the primary packaging 20 and the underside of the vacuum chamber 12. In this embodiment, the sealing device 14 comprises an outer silicone cup 14A and a tubular insert 14B with an upper flange, wherein the sealing device 14 is also interchangeable, so that the seal can be easily adapted to the outer diameter of the closure component 30 or thecan be adapted to the inner diameter of the receiving volume 23 and to the distance required between the primary packaging 20 and the vacuum chamber 12 along the longitudinal axis L of the primary packaging 20 for correct positioning of the closure component 30 in the receiving volume 23 of the primary packaging 20.

[0106] Inserting the closure component 30 into the receiving volume 23 using such a vacuum device or under negative pressure has the advantage that, firstly, the pressure forces or insertion forces for inserting the closure component 30 can be reduced, since the air located in the receiving volume 23 above the formulation 27 does not need to be compressed during insertion. Furthermore, the pressure in the space formed between the formulation 27 and the closure component 30 can be significantly reduced in this way compared to the pressure that would arise if no negative pressure were created in the receiving volume 23 during insertion of the closure component 30. In particular, with the help of such a vacuum device, the pressure in the volume between the formulation 27 and the closure component 30 can be reduced to a pressure that is no greater than ambient pressure.This allows for a particularly secure closure of the primary packaging 20. In particular, it reduces the risk that the closure component 30 will be forced upwards towards the opening 21 of the receiving volume 23 of the primary packaging 20 when the closed primary packaging 20 heats up, due to the expansion of an air volume enclosed between the formulation 27 and the closure component 30.

[0107] Vacuum devices of this type are generally known from the prior art, to which reference is made for further details on the design and operation of such vacuum devices.

[0108] For the correct placement of the closure component 30, it is important that the primary packaging material 20 is correctly positioned and aligned with respect to the closure device 200.

[0109] To ensure that the closure component 30 is not inserted at an angle or at an oblique angle into the receiving volume 23, the insertion direction E of the closure component 30 must coincide with the longitudinal axis L of the receiving volume 23, and in particular, be aligned with it. This can be achieved by positioning and aligning the primary packaging material 20 in the system 1000, and in particular by positioning and aligning it relative to or within the closure device 200, such that the longitudinal axis L of the receiving volume 23 of the primary packaging material 20 coincides with the direction of movement V of the setting piston 11 of the closure device 200, and in particular, is aligned with it and runs along a common straight line.

[0110] Secondly, for the closure component 30 to be correctly positioned, the primary packaging material 20 must also be located at a defined position along the first system axis A or along the direction of movement V of the setting piston 11 when the closure component 30 is placed, in order to ensure that the closure component 30 is located at the desired, defined position after placement, whereby this defined position depends on the stroke of the setting piston 11. In the present case, with a syringe 20 as the primary packaging material 20 and a stopper 30 as the closure component 30, the defined, desired position of the closure component 30, i.e., its ideal target position P (see figure 1), is located at the point where the closure component 30 is placed. Fig. 3 ), in particular above the formulation containing a pharmaceutical composition 27 within the absorption volume 23 at a defined distance from the surface of the formulation 27.

[0111] Fig. 2 Figure 1 shows examples of pre-filled and subsequently sealed primary packaging materials 20 in the form of syringes 20, which have been sealed with a closure component 30 in the form of a stopper 30, the stopper 30 being fully inserted into the corresponding receiving volume of the primary packaging materials 20. However, in some of the primary packaging materials 20 shown, for example, the middle primary packaging material 20 marked with a reference number, the stopper 30 is not in the desired predefined position, but rather too far above the composition in the receiving volume. This can occur, in particular, if the primary packaging material 20 is not correctly positioned in the system 1000 during the sealing process, i.e., when inserting the closure component 30.is positioned relative to the closure device 200, so that a sufficient seal between the primary packaging material and the vacuum chamber could not be achieved and thus a sufficient negative pressure could not be built up in the receiving volume of the primary packaging material, and / or if the position of the primary packaging material 20 along the direction of movement V of the setting piston 11, i.e. along the first system axis A in the system, was not correct or was not sufficiently aligned with the stroke of the setting piston 11.

[0112] With a primary packaging holder according to the invention, such as a primary packaging holder 100, as shown in Fig. 1 As schematically indicated and described in more detail later in this application, a correct insertion of the closure component 30 into the primary packaging material 20 can be achieved in a simple manner, since a primary packaging material holder according to the invention enables correct positioning and alignment of the primary packaging material 20 in a simple manner.

[0113] For correct positioning and alignment of the primary packaging material 20, the exemplary primary packaging material holder 100 has a first positioning axis Z and is designed to hold the primary packaging material 20 in a defined position along this first positioning axis Z and with a defined orientation of the longitudinal axis L of the receiving volume 23 of the primary packaging material 20 relative to the first positioning axis Z. This embodiment of a primary packaging material holder 100 is designed and arranged in the system 1000 such that the first positioning axis Z of the primary packaging material holder 100 coincides with the first system axis A or with the direction of movement V of the setting piston 11 of the closure device 200, i.e., is aligned with it.

[0114] This primary packaging holder 100 is further designed to receive the primary packaging 20, which has an outer surface 24 with a first section 24A and a second section 24B, in such a way that the primary packaging 20 with these sections 24A and 24B of the outer surface 24 of the primary packaging 20 rests against the primary packaging holder 100, in particular over a surface, such that when it is correctly received by the primary packaging holder 100, it is correctly positioned and aligned, i.e., it is located at the desired, defined position along the positioning axis Z or along the first system axis A or along the direction of movement V, and furthermore, the longitudinal axis L of the receiving volume 23 of the primary packaging 20 coincides with the direction of movement V of the setting piston 11, i.e., is aligned with it.

[0115] This primary packaging holder 100 is designed to correctly position and align the primary packaging 20, which is in particular a syringe 20, by receiving the primary packaging 20 in such a way that, on the one hand, it can be brought into contact with a first surface of the primary packaging holder 100 with a first surface of an underside of a rim 22 or a flange 22, which forms the first section 24A of the outer surface 24 of the primary packaging 20, specifically with a Fig. 1 unspecified positioning contact surface (see below). Fig. 5 , positioning contact surface 111). On the other hand, the primary packaging holder 100 is designed to receive the primary packaging 20, here a syringe 20, in such a way that the primary packaging 20, in a state correctly received by the primary packaging holder 100, and in particular simultaneously, with at least a part of the outer surface of the primary packaging 20, which forms the second section 24B of the outer surface, rests against a further alignment contact surface of the primary packaging holder, which is also not specified in detail here (cf. Fig. 6 , alignment contact surfaces 112 and 122).

[0116] If the primary packaging material 20, with its two sections 24A and 24B of its outer surface 24, lies flat against the corresponding contact surfaces (the positioning contact surface and the at least one alignment contact surface) of the primary packaging material holder 100, in particular simultaneously, a primary packaging material 20 received by the primary packaging material holder 100 is aligned in the primary packaging material holder 100. If the primary packaging material holder 100 is correctly positioned and aligned in the system 1000, as shown in Fig 1 As shown schematically, this also results in a correct alignment and positioning of the primary packaging material 20 in the system 1000 and a correct insertion of the closure component 30 is possible.

[0117] The detailed design of the primary packaging holder 100 will be described in more detail later in this application, in particular with reference to the Fig. 5 bis 13 .

[0118] Fig. 3 Figure 1 shows, in an enlarged schematic representation for better understanding, an example of a primary packaging 20 in the form of a syringe 20, closed with a closure element 30 in the form of a stopper 30. The syringe 20 is pre-filled with a formulation containing a pharmaceutical composition 27, and the closure element 30 is located at a predefined position P above the formulation 27, such that a space 40 (in particular an air space) with a defined volume is formed in the space between a surface of the formulation 27 and a bottom surface of the closure element 30. The stopper 30 was inserted into the receiving volume 23 through the upper (first) opening 21. The composition 27 can be dispensed from the syringe 20 through the second opening 28 of the receiving volume 23 at the lower end of the syringe 20 during use.Depending on how much the receiving volume 23 has been vacuum-sealed when the closure component 30 is inserted, there is more or less air in this space 40, or according to the specified desired position of the VB in the PM, in particular of the stopper in the syringe, the vacuum is applied accordingly in the procedure for closing the PM in order to achieve the position of the VB and thus the air space as predefined.

[0119] In this illustration, the rim 22 or flange 22 of the primary packaging 20, as well as its underside 25, which forms the first section 24A of the outer surface 24 of the primary packaging 20, are clearly visible. The outer surface 24B, which forms at least part of the second section 24B, is also clearly visible.

[0120] Figures a) to f) in Fig. 4 further exemplary individual and detailed views in enlarged representation of prefilled and subsequently sealed syringes 20 with different positions of the stopper 30 in the receiving volume 23 of the syringe 20, some stoppers 30 being properly inserted and others being defective.

[0121] Figure a) in Fig. 4 Figure 30 shows, as an example, a plug that is still positioned within the marking lines and thus sufficiently correctly placed in the vertical direction. The corresponding enlarged representation of the plug in Figure b) shows... Fig. 4 However, it is evident that the insertion quality of the plug 30 is defective, which is symbolically indicated here by the reference arrow with the reference symbol Q, since an underside of the plug 30, in particular a lower sealing lip of the plug 30, is crushed and therefore cannot fulfill its full function. The cause of this is primarily a slight tilting of the plug 30 during insertion into the receiving volume 23 due to an inaccurate alignment of the primary packaging material 20, here the syringe 20, relative to the direction of movement V of the setting piston 11. The associated syringe 20 was held by a conventional primary packaging material holder during the insertion of the plug 30, which did not allow for sufficiently precise alignment of the primary packaging material 20. In particular, the longitudinal axis L of the receiving volume 23 was not correctly aligned with the direction of movement V of the setting piston 11.The insertion direction E of the plug 30 was not aligned with it, i.e., it was not aligned or ran along a common straight line. Consequently, the plug 30 was inserted through the opening 21 into the receiving volume 23 at a slight angle, and the sealing lip on its underside was pinched.

[0122] Figure c) in Fig. 4 Figure 20 shows a syringe 20 sealed with a stopper 30, in which the stopper 30 is not completely within the predefined area, but is positioned too far above it, as can be seen in the corresponding enlarged view in Figure d). Fig. 4 This is clearly visible. Therefore, this stopper 30 is also not correctly positioned. This error can generally be attributed to an incorrect and thus faulty positioning of the primary packaging material 20 along the insertion direction E of the stopper 30 or the direction of movement V during the placement of the closure component 30, whereby the primary packaging material 20 was positioned too low or at too great a distance from the closure device and / or due to insufficient negative pressure or too much residual air volume in the receiving volume 23 above the composition. In this case, the cause was that the syringe 20 was also held by a conventional primary packaging material holder during the insertion of the stopper 30, with which sufficiently precise positioning of the primary packaging material 20 could not be achieved.In particular, the primary packaging material 20 was not positioned at a correct distance along the direction of movement V of the setting piston 11 or the insertion direction E of the plug 30 relative to the closure device 200, especially to the setting piston 11, but in particular too far below it, so that the plug 30 could not be pushed far enough into the receiving volume 23 by the setting piston 11 with the set stroke of the setting piston 11.

[0123] Figure e) in Fig. 4 Figure f) shows a correctly placed plug 30, correctly and without error inserted into the receiving volume 23. Fig. 4 Figure 1 shows a corresponding enlarged view in the area of ​​the plug 30. Here, the associated syringe 20 was removed from the primary packaging holder 100 according to the invention during the insertion of the plug 30. Fig. 1 held, with which both a sufficiently accurate positioning and a sufficiently accurate alignment of the primary packaging material 20 could be achieved.

[0124] With a primary packaging holder according to the invention, for example with a primary packaging holder 100, as shown in Fig. 1 schematically indicated and described in more detail later in this application, in particular with reference to the Fig. 5 bis 13 , can the risk be assessed based on Fig. 2 as well as the figures a) to d) from Fig 4 The described errors are reduced and correct insertion of the closure component 30 into the primary packaging material 20 is achieved in a simple manner, since a primary packaging material holder according to the invention enables correct positioning and alignment of the primary packaging material 20 in a simple manner.

[0125] The Fig. 5 bis 13 The illustrations show various views with details of a possible design of the primary packaging holder 100 described here as an example, beginning with the Fig. 5 bis 7 will be described in more detail.

[0126] Fig. 5 Figure 100 shows, in a perspective view from an oblique angle above, details of a possible embodiment of a primary packaging holder according to the present invention, using the primary packaging holder as an example. Fig. 5 a section of the primary packaging holder 100 according to the invention Fig. 1 with the primary packaging material 20 included therein in the form of the syringe 20 during the closing process, wherein the syringe 20 is closed by means of a Fig. 5 The stopper 30, which is not shown, is closed and is inserted into the receiving volume 23 of the syringe 20 prefilled with a formulation via the first opening 21 by means of the closure device 200.

[0127] Fig. 6 shows the complete primary packaging holder 100 from Fig. 5 together with an embodiment of a guide rail 150 as part of an embodiment of an arrangement 500 according to the invention and in another perspective view and without a primary packaging material 20 included therein, wherein in this view the fastening of the primary packaging material holder 100 to the guide rail 150 by means of the screw 118 mentioned above is indicated.

[0128] Fig. 7 The primary packaging holder 100 shows from the Fig. 5 and 6 in another perspective view, also without a primary packaging material shown 20.

[0129] For the precise positioning and alignment of the primary packaging material 20, the primary packaging material holder 100 has a receiving device 110, which in this example of a primary packaging material holder 100 has a first holding arm 113 extending perpendicular to a first positioning axis Z of the primary packaging material holder 100, which is attached to a Fig. 5 unspecified body of the receiving device 110 in the form of a mounting sleeve (see Fig. 7 , fastening sleeve 127) is fastened by means of a fastening means 118 in the form of a screw 118, wherein in this embodiment of a primary packaging holder according to the present invention the first positioning axis Z extends in the system 1000 in particular in a vertical direction when the primary packaging holder 100 is correctly positioned and aligned, so that the first holding arm 113 extends in particular in a horizontal direction.

[0130] The receiving device 110 or the primary packaging holder 100 can also be mounted on a guide rail 150 (see) via the screw 118, which extends through a through hole 117 along a fastening axis B through the fastening sleeve. Fig. 6 ) and are attached, positioned and aligned via these in the system 1000, which will be explained in more detail later.

[0131] The first retaining arm 113 has an outer surface 114, which is at least partially formed by a top surface of a first component 115A in the form of a Y-clip inserted into the first retaining arm 113, which is fixed in the first retaining arm 113 at a desired position by means of a further fastening element 116, which is also a screw 116, wherein the retaining arm 113 has an elongated hole (not shown) for precise alignment of the Y-clip 115A in the retaining arm 113 in the direction of the double arrow, and the component 115A is designed such that it can be inserted into the first retaining arm 113 with sufficient play for precise alignment and can be fixed in the desired position in the first retaining arm 113.

[0132] The Y-clip 115A serves as a holding and positioning element for holding and positioning the primary packaging 20 in the primary packaging holder 100, wherein a part of the upper surface of the holding and positioning element 115A forms the first positioning contact surface 111, by means of which the primary packaging 20 can be correctly positioned in the primary packaging holder 100 along the first positioning axis Z. A primary packaging 20 received by the primary packaging holder 100 is correctly positioned along the first positioning axis Z when a first section 24A of its outer surface 24 rests against the positioning contact surface 111 of the primary packaging holder 100, in particular over its entire area.In this embodiment, the positioning contact surface 111 extends in a plane perpendicular to the positioning axis Z of the primary packaging holder 100, and thus, in this case, in a horizontal direction. Depending on the primary packaging 20 to be accommodated, the positioning contact surface 111 may also be designed differently and / or have a different orientation, particularly relative to the positioning axis Z.

[0133] If the primary packaging material 20 is a syringe 20, as in the present embodiment, the syringe 20 is correctly positioned along the first positioning axis Z and thus positioned at the correct distance to the vacuum chamber 12 or to the closure device 200, so that, on the one hand, a good seal between the underside of the vacuum chamber 12 and the primary packaging material 20 can be achieved by means of the sealing device 14, and on the other hand, the closure component can be placed at the desired, predefined position P along the longitudinal axis L of the primary packaging material 20 in its receiving volume 23 (see Figure 14). Fig. 3 ), when the syringe 20 with an underside 25 of the rim or flange 22, which forms the first section 24A of the outer surface 24 of the syringe 20, is in contact with the first positioning contact surface 111, in particular over a surface.

[0134] The vertical position of the primary packaging holder 100 in the system 1000, in particular along the first system axis A or along the direction of movement V of the closure device 200, as well as the vertical position of the positioning contact surface 111 along this axis, which can be easily adjusted by replacing the component 115A, in particular by changing the thickness d of the Y-clip 115A (see Fig. 7 The position of a primary packaging element 20 to be closed, which is held by the primary packaging holder 100, can be easily adjusted along the positioning axis Z, thus enabling correct placement of the closure component. In particular, a defined distance D from the positioning contact surface 111 to the closure device 200 can be set, thereby establishing a defined position along the positioning axis Z of a primary packaging element 20 correctly held by the primary packaging holder 100.

[0135] In addition to the precise positioning of a primary packaging 20, the primary packaging holder 100 also enables the precise alignment of the longitudinal axis L of the receiving volume 23 of a primary packaging 20 received by the primary packaging holder, in particular aligned with the first positioning axis Z of the primary packaging holder 100, and, with correct positioning and alignment of the primary packaging holder 100 in the system 1000, consequently also an alignment of the longitudinal axis L of the receiving volume 23 of a primary packaging 20 relative to the closure device 200, in particular aligned with the direction of movement V of the closure device 200, in particular aligned with the setting direction E of the closure component 30 (see figure). Fig. 1 ).

[0136] This example of a primary packaging holder 100 also has two alignment contact surfaces 112 and 122 (see Fig. 6 ), which in this primary packaging holder 100 extend in a direction parallel to the positioning axis Z and thus in this case in a perpendicular direction, and to which the primary packaging 20 also abuts with a second section 24B of the outer surface of the primary packaging 20 when the primary packaging 20 is correctly inserted into the primary packaging holder 100 or is properly received by it.

[0137] The alignment contact surface 112, which is also assigned to the first retaining arm 113 and also forms part of the outer surface 114 of the first retaining arm 113, is part of a second component 115B inserted into the first retaining arm 113, which is also formed by a Y-clip 115B. The Y-clip 115B is also attached to the first retaining arm 113 by means of the screw 116, but unlike the upper Y-clip 115A, it is not inserted into the first retaining arm 113 from above, but from below. In contrast to the upper Y clip 115A, the lower Y clip 115B does not serve as a holding and positioning element for holding and positioning the primary packaging 20 along the positioning axis Z, but rather for aligning the longitudinal axis L of the primary packaging 20 relative to the positioning axis Z, specifically for aligning the longitudinal axis L along the positioning axis Z, i.e., flush with it, with the alignment contact surface 112 of the Y clip 115 in the Fig. 6 the Y-direction of the primary packaging holder 100, in particular, protrudes further into the recess 130 (see Fig. 7 ), into which the primary packaging material 20 can be inserted, particularly laterally, for example in the horizontal direction Y, as the corresponding surface of the upper Y-clip 115A, which comprises the positioning contact surface 111. This ensures that the primary packaging material 20, with its second section 24 B of its outer surface 24, can actually be brought into contact with the alignment contact surface 112 in order to achieve the desired, precise and correct alignment of the longitudinal axis L of the primary packaging material 20.

[0138] By means of the second alignment contact surface 122, which also extends parallel to the positioning axis Z, but is spaced apart from the first alignment contact surface 112, in particular at a certain distance below it, a particularly good alignment of the primary packaging material 20 in the primary packaging material holder 100 can be achieved.

[0139] In the embodiment of the primary packaging holder 100 shown here, the second alignment contact surface 122 is formed by a part of an outer surface 124 of a second retaining arm 123, in particular by a part of an outer surface of a further component 125B in the form of a Y clip, which is inserted into the second retaining arm 123 from an underside, analogous to the previously described Y clip 115B.

[0140] Like the first retaining arm 113, the second retaining arm 123 also has a component 125A in the form of a Y-clip 125A inserted from the top of the retaining arm 123, wherein the two Y-clips 125A and 125B are also fixed in the associated second retaining arm 123 by means of a common fastening element 126 in the form of a screw, i.e. at a defined position.

[0141] In order to securely hold a primary packaging 20 received by the primary packaging holder 100, the Y-clips 115B and 125B of the primary packaging holder 100 shown as an example each have clamping arms 131 and 141 respectively, which are elastically spring-like along the X-direction shown, as indicated by the corresponding double arrow in front of the outer end of the clamping arms 131 and 141 respectively. Fig. 6 As indicated, when a primary packaging element 20 is inserted laterally in the Y-direction into the primary packaging holder 100, the clamping arms 131 and 141 are pushed outwards in the X-direction to a greater or lesser extent, depending on the outer diameter of the primary packaging element 20. Once the primary packaging element 20 has been inserted far enough in the Y-direction into the primary packaging holder 100, the clamping arms spring back. This ensures that the primary packaging element 20 is securely held, or in particular, "clamped," in the Y-direction within the primary packaging holder 100.

[0142] To ensure sufficient "outward pushing" or sufficient widening of the recess 130 (see Fig. 7 ) to enable damage-free insertion of the primary packaging material 20 into the primary packaging material holder 100, the first holding arm 113 and the second holding arm 123 each have corresponding movement ranges 132 and 142 between an outer surface of the clamping arms 131 and 141 and a web 119 or 129 of the respective holding arm 113 or 123, which allow a sufficiently springy and elastic movement of the clamping arms 131 and 141 in the Y direction, but at the same time also limit the range of motion of the clamping arms 131 and 141 in this direction.

[0143] Since the two Y-clips 115B and 125B each serve both to align the primary packaging material 20 in the primary packaging material holder 100 and to secure or clamp the primary packaging material 20, they can also be referred to as alignment and securing elements 115B, 125B or as alignment and clamping elements 115B, 125B.

[0144] In principle, it is also conceivable, instead of combining at least two functions in at least one of these Y-clips as with the Y-clips 115B and 125B, to provide a separate component for each function, as with the primary packaging holder 100, wherein the individual components are preferably arranged one above the other along the positioning axis Z with the component with the positioning contact surface 111 at the very top, or if the primary packaging 20 is not to be held hanging as with the primary packaging holder 100, but standing upright, at the very bottom with the positioning contact surface 111 pointing upwards.

[0145] It is also possible to integrate more than two functions into one of these Y-clips, or to omit the lower retaining arm 123 with the two lower Y-clips 125A and 125B, provided that the extent of the alignment contact surface 112 of the Y-clip 115B parallel to the positioning axis Z is sufficiently large to achieve the required precision in aligning the longitudinal axis L of the primary packaging 20 in the primary packaging holder. In many cases, this can be achieved, for example, by ensuring that the Y-clip 115B is sufficiently thick.

[0146] In each embodiment of a primary packaging holder described herein, one or more receiving elements can have an anti-slip coating on one or more surfaces, or the material of the receiving element can be post-processed to a desired roughness, preferably Ra 0.4 µm to less than or equal to Ra 0.8 µm, so that the receiving element has greater frictional resistance on the surface against which the surface of the primary packaging is applied. In one embodiment, the receiving element has a coating of a suitable material that is permitted for use in cleanroom class A and is resistant to sterilizing and / or disinfecting agents such as hydrogen peroxide (H₂O₂), or the receiving element is made of such a material.

[0147] For precise positioning and alignment of a primary packaging 20 held by the primary packaging holder 100, the primary packaging holder 100 has various adjustment options. Firstly, as already explained by way of example in connection with the Y-clip 115A, all Y-clips 115A, 115B, 125A and 125B can each be replaced and inserted into the primary packaging holder 100, in particular into the respective holding arms 113 and 123, by a corresponding, different Y-clip with a modified geometry adapted in particular to the respective primary packaging material 20 to be accommodated, and fixed accordingly in the desired position by means of the fastening means 116 and 126, whereby the Y-clips 115A, 115B, 125A and 125B can in particular each be finely adjusted in their position by means of an elongated hole in the Y direction in the respective holding arm 113 or 123.This allows, in particular, an inclination of the longitudinal axis L of the receiving volume 23 of a primary packaging material 20 to be received about an axis parallel to the one in . Fig. 6 The X direction shown can be set.

[0148] Furthermore, in particular to incline the longitudinal axis L of the receiving volume 23 of a primary packaging material 20 to be received about an axis parallel to the one in Fig. 6 to adjust the drawn Y-direction, an angle of the lower support arm 123 within defined limits, in particular in a range of -5° to +5°, around the mounting axis B (see Fig. 5 ) are adjusted, wherein the lower retaining arm 123 is mounted on the mounting sleeve 127 about the mounting axis B so as to be rotatable relative to the upper retaining arm 113 at least within certain limits and is secured by means of a screw not shown in detail here (see Fig. 10 , fastening screw 134), which can be screwed into a fastening hole 128 (see Fig. 7 and Fig. 10 ) can be fixed in its desired angular position around the mounting axis B.

[0149] In a particularly advantageous embodiment of a primary packaging holder 100, all components of the primary packaging holder 100 against which the primary packaging rests during closure are made of plastic, for example, polytetrafluoroethylene (PTFE), Teflon®, or another synthetic fluoropolymer, in order to easily prevent damage to the primary packaging 20. In particular, the components 115A, 115B, 125A, and 125B, which are designed here in the form of Y-clips, can be made of plastic, while the remaining parts and components of the primary packaging holder 100 can be made of metal or may contain metal, especially stainless steel for hygienic reasons.

[0150] The Fig. 8 bis 10 show different views of the primary packaging holder 100 from the Fig. 5 bis 7 or of assemblies and individual parts of this primary packaging holder 100.

[0151] Fig. 8 Figure 1 shows a perspective view from below of the primary packaging holder 100, in which the Y-clips 115B and 125B, inserted from below into the respective holding arms 113 and 123 respectively, are particularly visible, along with their clamping arms 131 and 141 and the associated movement ranges 132 and 142, which are each limited by a web 119 and 129 of the respective holding arm 113 and 123, respectively. Sufficient movement range 143 of the clamping arms 131 and 141 must also be provided on the inside (see Figure 1). Fig. 9 ). Also clearly visible is the mounting sleeve 127, via which the primary packaging holder 100 is mounted on the guide rail 150 (see figure). Fig. 6 ) can be attached, the fastening sleeve 127 having a corresponding recess 133 at its lower end for a rotationally secure attachment, which can engage with a corresponding projection on the guide rail 150. Furthermore, the lower ends of the fastening screws 116 and 126 are clearly visible with their associated external threads, which each engage in a corresponding internal thread of a fastening hole 136 of a fastening plate 135, which is also inserted from below into the respective retaining arm 113, 123 (see Fig. 10 , mounting hole 136 in the mounting plate 135), to securely fix the Y clips 115A, 115B, 125A, 125B in their position on the corresponding holding arm 113, 123.

[0152] Fig. 9 Figure 1 shows a perspective view from below of the first retaining arm 113 in a state removed from the primary packaging holder 100 and without the associated fastening screw 116 and without the associated mounting plate. This illustration shows that the lower Y-clip 115B of the first retaining arm 113 is for a defined positioning within the first retaining arm 113, particularly in the Y direction (see Figure 1). Fig. 6 ), has a corresponding through-hole 144 through which the fastening screw 116 can be passed, by means of which the Y-clip 115B can be fixed to the first retaining arm 113 in the desired position. This illustration also shows the through-hole 117 in the first retaining arm 113 for the fastening screw 118, by means of which the entire primary packaging holder 100 can be attached to the guide rail 150, as well as a receiving bore 145 by means of which the first retaining arm 113 can be placed onto the mounting sleeve 127 from above.

[0153] Fig. 10 Figure 1 shows a perspective view from a slightly oblique angle of some individual parts of the described primary packaging holder 100. The elongated holes 146 and 147 for fine-tuning the position of the Y-clips 115A, 115B, 125A and 125B in the holding arms 113, 123 in the Y-direction are particularly visible (see Figure 1). Fig. 6 ).

[0154] Fig. 11 shows a side view of the primary packaging holder 100 from the Fig. 5. bis 10 in a state installed in the system 1000 with the closure device 200, with a primary packaging 20 in the form of a syringe 20 held by the primary packaging holder 100, looking towards the upper retaining arm 113, during a closure process, wherein in this illustration the sealing device 14 is located above the flange 22 of the primary packaging 20. It is clearly visible in this illustration how the primary packaging 20 is sealed with an underside of its edge or...The flange 22, which forms a first section 24A of the outer surface of the primary packaging 20, rests on the upper side of the first retaining arm 113, in particular on the positioning contact surface 111 formed by it, which is part of the upper Y-clip 115A, and how the primary packaging 20 further rests with a part of its outer surface 24, which forms a second section 24B of the outer surface 24 of the primary packaging 20, against the alignment surface 112 of the first retaining arm 113, which is formed by the lower Y-clip 115B. It is also clearly visible how the primary packaging 20 is securely held in the primary packaging holder 100 by the clamping arms 131 of the lower Y-clip 115B.

[0155] Fig. 12 shows a perspective view of the primary packaging holder 100 from Fig. 11 with the primary packaging material 20 before the closing process, wherein the primary packaging material 20 is already pre-filled (the formulation with which the primary packaging material 20 is pre-filled is not shown). In this figure, it is also clearly visible how the primary packaging material 20, with a part of its outer surface 24, which forms the second section 24B of the outer surface 24 of the primary packaging material 20, rests against the alignment surface 122 of the second retaining arm 123, which is formed by the lower Y-clip 125B of the second retaining arm 123, and is also held in the primary packaging holder 100 by its clamping arms 141.

[0156] Fig. 13 shows how Fig. 6 , embodiment 500 of an arrangement according to the invention with the guide rail 150 and an embodiment of a primary packaging holder according to the invention, wherein the primary packaging holder in this case is the primary packaging holder 100 made from the Fig 5 bis 12 is. Fig. 13 The arrangement 500 is further shown in a state installed in the system 1000, in which a gripping device 160 can also be seen, by means of which a primary packaging material 20 to be sealed can first be transported parallel to the guide rail 150 and placed directly in front of the primary packaging material holder 100, in order to then be inserted laterally into the recess 130 in the primary packaging material holder 100 by means of the gripping device 160.

[0157] Fig. 14a bis 14g show various embodiments of primary packaging materials 20 in accordance with the invention, wherein the Fig. 14a, 14b, 14f und 14g Various primary packaging materials 20, designed as syringes with a rim or flange 22 with a bottom, are shown, which are closed by means of a closure component 30 in the form of a stopper.

[0158] Fig. 14c Figure 1 shows a two-chamber cartridge 20 with a bottom surface 25, a partially surrounding rim 22, and a neck 26. The cartridge is closed by means of two closure components 30. The closure component 30 can be a suitable plug, with or without a Luer lock, a suitable cap, with or without a Luer lock, or a plug and a cap, with or without a Luer lock.

[0159] Fig. 14d Figure 1 shows a carpule 20 with a receiving volume 23 and an underside 25 of the partially surrounding rim 22. The carpule is closed by means of a closure component 30. The closure component 30 can be a suitable plug, with or without a Luer lock, a suitable cap, with or without a Luer lock, or a plug and a cap, with or without a Luer lock.

[0160] Fig. 14e Figure 1 shows a cartridge 20 with a receiving volume 23 and a bottom surface 25 of the partially surrounding rim 22. The cartridge is closed by means of a closure component 30. The closure component 30 can be a suitable plug, with or without a Luer lock, a suitable cap, with or without a Luer lock, or a plug and a cap, with or without a Luer lock.

[0161] Fig. 15 Figure 500 shows the embodiment of the arrangement according to the invention in a state installed in the system 1000, wherein the system 1000 is in particular a filling system. Here too, the arrangement 500 comprises the guide rail 150 and the primary packaging holder 100 made of the Fig. 5 bis 13 , where the section of plant 1000 shown here also includes the closure device 200 of plant 1000. The primary packaging holder 100 is shown with a primary packaging material 20 in the form of a syringe 20.

[0162] This figure clearly shows the vacuum device with the vacuum chamber 12, the setting piston 11, an associated guide device 201 for guiding the setting piston 11, and the flange 13A of the setting tube. The sealing device 14 seals a gap between the primary packaging 20 and the vacuum chamber 12, so that air can be efficiently extracted from the receiving volume 23 of the primary packaging 20 by means of the vacuum device and the primary packaging 20 can be securely sealed with the closure component 30.

[0163] For precise positioning and alignment of the primary packaging material 20 with its longitudinal axis L relative to the closure device 200, and thus precise and correct insertion of a stopper 30 as a closure component 30 into the syringe 20, the primary packaging material holder 100 is positioned and aligned in the system 1000, in particular attached to the guide rail 150, such that the positioning axis Z of the primary packaging material holder 100 coincides with the system axis A, which is defined by the direction of movement V of the closure device 200, in particular the direction of movement of the setting piston 11, and thus corresponds to the (insertion) direction E of the closure component 30.This allows the primary packaging material 20 to be aligned by means of the primary packaging material holder 100 such that the longitudinal axis L of the primary packaging material 20, when properly held by the primary packaging material holder 100, coincides with the first system axis A and thus with the direction of movement V of the closure device 200, in particular the direction of movement of the setting piston 11, i.e., is aligned with it and runs along a common straight line. This prevents, in particular, the locking component 30 from tilting during placement for closing.

[0164] For a defined positioning of the closure component 30 along the longitudinal axis L of the primary packaging 20, the primary packaging holder 100 is furthermore arranged and fastened at a defined position in the (vertical) direction of the first system axis A, i.e., at a defined height along this axis A, in the system 1000, in particular by means of the guide rail 150, which in particular has a suitable design for this purpose, and in particular a corresponding height. The position of the first retaining arm 113, which defines the final height of the primary packaging 20 in the holder during closure via the positioning contact surface 111, can alternatively or additionally be determined by selecting a fastening sleeve 127 (see Figure 1). Fig. 10 ) with a different length and / or using more or fewer thinner or thicker spacers (not shown) that can be inserted into the receiving bore 145 (see Fig. 9 ).

[0165] Fig. 16 For better understanding, another perspective view of the primary packaging holder 100 is shown. Fig. 15 in the plant 1000, however without primary packaging material 20 and without the closure device 200, but with the gripping device 160 from Fig. 13 for positioning a primary packaging material 20 in the primary packaging material holder 100, wherein in this illustration an associated transport device 170 is also recognizable, to which the gripping device 160 is attached and by means of which primary packaging materials 20 to be sealed can each be transported to the primary packaging material holder 100 and can be transported away after sealing, in particular parallel to the guide rail 150, in particular in its longitudinal direction.

[0166] The primary packaging holder 100 described here allows for precise and flexible adjustment, and thus precise and accurate positioning and alignment of a primary packaging unit 20. However, due to the many adjustment options, it is relatively complex to set up. The desired setting can be achieved very efficiently using an external calibration device and a suitable primary packaging gauge.

[0167] Fig. 17 shows the primary packaging holder 100 from the previous Figures 5 to 16In such an exemplary external calibration device 300 with an exemplary reference primary packaging gauge 320 for adjusting the primary packaging holder 100 as such for positionally accurate reception and precise alignment of an associated primary packaging 20. By means of the calibration device 300, which has a precisely manufactured receiving block 310 for attaching the primary packaging holder in order to enable in a simple manner an exact alignment of the first positioning axis Z of the primary packaging holder, in particular a vertical alignment, and the gauge 320, in particular the holding arms 113 and 123 can be precisely and correctly aligned to each other and accordingly attached to the mounting sleeve 127.Likewise, the positions of the Y-clips 115A, 115B, 125A and 125B, which are required to properly receive a respective primary packaging material 20 with a defined and desired position along the positioning axis Z, i.e. in particular with a defined height along this axis Z, and with its longitudinal axis L correspondingly and correctly aligned to this positioning axis Z, in particular in line with it (see e.g. Fig. 6 ), in this way they can be determined and adjusted efficiently and easily.

[0168] Fig. 18Figure 1 shows a section of a further embodiment of an arrangement 500' according to the invention, comprising a further embodiment of a guide rail 150' and a further embodiment of a primary packaging holder 400 according to the present invention, in a perspective view from an oblique angle above. This primary packaging holder 400 is essentially a single piece and made of plastic, for example, polytetrafluoroethylene (PTFE), Teflon®, or another synthetic fluoropolymer, so that the adjustment effort can be significantly reduced with this primary packaging holder 400. However, precise manufacturing of the primary packaging holder 400 is necessary to achieve the required accuracy in positioning and alignment of the primary packaging 20 for closing the primary packaging 20 to be received.

[0169] In this primary packaging holder 400, the functions of the Y-clips 115A and 115B from the primary packaging holder 100 are integrated into the first holding arm 113, as symbolized by the use of the same reference numerals. The holding arm 113 simultaneously serves as a holding, positioning, alignment, and clamping element. For improved alignment, particularly as shown in Fig. 24a shown, a second holding arm 123 is provided, in which the functions of the Y-clips 125A and 125B of the primary packaging holder 100 are integrated.

[0170] This primary packaging holder 400 is also designed to be mounted on a guide rail 150', but according to a different principle, in particular by means of two fastening means 118, which can also be designed as fastening screws 118 as schematically indicated, and which are in particular arranged offset from each other and are each guided through corresponding through holes 117 with a certain amount of play, so that an alignment of the primary packaging holder in the longitudinal direction of the guide rail 150' (cf. X-direction in Fig. 6 ) and in a direction perpendicular to it, parallel to a plane of the longitudinal direction of the guide rail 150' (see Y-direction in Fig. 6 ) is possible and thus in a horizontal plane F (cf. Fig. 22 ).

[0171] For setting a defined angular position of the primary packaging holder around a (vertical) axis perpendicular to the plane with the longitudinal direction of the guide rail 150' (see Z-direction in Fig. 6 ), the primary packaging holder 400 is furthermore slightly rotatable about a mounting pin 151 of the guide rail 150', which, with reference to the illustration in Fig. 18 extends vertically upwards. This guide rail 150' can also be fixed in a system, particularly at a defined position, via one or more mounting holes 152.

[0172] For screwing the fastening screws 118 to the guide rail 150', the latter has corresponding, offset positioning fastening holes 153 with internal threads, which are located, for example, in Fig 19 are easily recognizable, whereby Fig. 19 a view from below of a section of the 500' arrangement Fig. 18This illustration also clearly shows the second holding arm 123, into which the functions of the Y-clips 125A and 125B of the primary packaging holder 100 are integrated, which is also symbolized by the use of the same reference symbols.

[0173] For improved fastening and / or positioning of the guide rail 150' or the arrangement 500' in an associated system, a plastic sleeve 154 can be inserted into a corresponding receiving bore on the underside of the guide rail 150', in particular into a corresponding alignment block 155 with such a receiving bore, as shown in Fig. 20 shown, which provides a perspective view of the underside of the 500' arrangement from the Figs. 18 and 19 shows.

[0174] Fig. 21 shows a perspective view of a section of the guide rail 150' from the arrangement 500' from the Figs. 18 to 20in a detailed representation, wherein the guide rail 150' has several mounting pins 151 and several pairs of positioning mounting holes 153 for receiving several primary packaging holders 400 as shown in Fig. 18 shown.

[0175] Fig. 22 shows a different perspective view of the 150' guide rail from the Figs. 18 to 21 in individual part representation, wherein this guide rail 150' is designed to accommodate a total of three primary packaging holders 400.

[0176] Fig. 23 Figure 118 shows exemplary fastening devices for attaching a primary packaging holder to a guide rail, for example for attaching the primary packaging holder 400 from the Figs. 18 to 20 on the guide rail 150' from the Figs. 18 to 22, wherein the fastening means 118 are fastening screws 118 with a shank 118A and an external thread 118B, which are designed to engage with the offset fastening holes 153 with internal thread in the guide rail 150'.

[0177] Fig. 24a The primary packaging holder 400 is shown. Fig. 18In a perspective view showing individual parts, but with modified fastening means 418, which in particular have a different head. In this representation, the essentially one-piece design of the primary packaging holder 400 of the two holding arms 113, 123 with the central body of the primary packaging holder 400 with the fastening recess 417 for the arrangement around the fastening pin 151 on the guide rail 150', as well as the identical design of the holding arms 113 and 123, and the integration of the functionality of the two Y-clips of the holding arms into a holding arm 113, 123, which is integrally connected with the rest of the holder, are particularly evident.

[0178] A defined distance H2 between the underside of the upper support arm 113 and the top side of the lower support arm 123 is also clearly visible.

[0179] For a particularly stable design, the primary packaging holder 400, as in this embodiment, can also have a web 416 extending between the support arms 113 and 123 with a first height H1. In other embodiments, the web 416 can have a lower height and, for example, extend only over the second height H2.

[0180] Fig. 24b shows a further embodiment of a primary packaging holder 400' according to the present invention, wherein this primary packaging holder 400' in contrast to the primary packaging holder 400 is made of Fig. 24a It has only one first retaining arm 113 and consequently only one first alignment contact surface 112, which is integrated into the first retaining arm 113. However, this may be sufficient in many cases.

[0181] Fig. 24cFigure 1 shows a further embodiment of a primary packaging holder 400" according to the present invention, which is designed like the primary packaging holder 400', but additionally has a further alignment contact surface 422 on the web 416, which extends in particular over the entire height H1 of the web 416. This allows for particularly good alignment of the primary packaging 20, as a particularly large contact surface for alignment in the primary packaging holder 400" can be provided in this way.

[0182] Fig. 24d Figure 1 shows a further embodiment of a primary packaging holder 400‴ according to the present invention, which is designed similarly to the primary packaging holder 400‴, but does not integrate an alignment contact surface 112 into the first holding arm 113.

[0183] Fig. 25aFigure 1 shows a further embodiment of a primary packaging holder 600 according to the present invention, which is designed similarly to the primary packaging holder 400 from the following. Fig. 18 and 24a , which, however, differs in the shape of the base body and in detail in the design of the retaining arms 113 and 123. Furthermore, this primary packaging holder 600 does not have a web 416.

[0184] Fig. 25b shows a further embodiment of a primary packaging holder 600' according to the present invention, which, like the primary packaging holder 400', is made of Fig. 24b only has a first holding arm 113 and consequently only a first alignment contact surface 112, which is integrated in particular into the first holding arm 113.

[0185] Figs. 26 and 27 various perspective views of the primary packaging holder 100 are shown. Fig. 15 and 16in the system 1000, but without the closure device, but with several gripping devices 160 for positioning a primary packaging material in the primary packaging material holder 100 and with a reference primary packaging material gauge 320 for aligning / calibrating the primary packaging material holder 100 within the system 1000, wherein the reference primary packaging material gauge 320 is held by a special alignment device 180, which is defined in the system 1000 and is positioned with its outer surface against the associated contact surfaces 112 and 122 of the primary packaging material holder 100.

[0186] Fig. 28 shows a perspective view obliquely from the side of the primary packaging holder 100 from the Fig. 15 , 16 , 26 and 27in a state aligned in the system 1000 with a primary packaging 20 received by the primary packaging holder 1000 during the closing process, wherein in this representation it is particularly easy to see how the individual axes or directions coincide and align with each other, in particular the system axis A, the positioning axis Z of the primary packaging holder 100, the longitudinal axis L of the primary packaging, the direction of movement V of the closing device and the (insertion) direction E of the closing component 30.

[0187] Fig. 29Figure 1 shows a flowchart for an embodiment of a method according to the invention for the schematic and exemplary explanation of individual process steps of a method for filling a primary packaging material 20 with a formulation containing a pharmaceutical composition 27, wherein the method described here by way of example includes, in addition to the optional steps S1 to S4 as well as S6 and S7, the mandatory step S5 and the associated sub-steps S5A and S5B, the process steps required for carrying out a method according to the invention for closing a primary packaging material 20.

[0188] To fill a primary packaging 20 with a formulation containing, in particular, a pharmaceutical composition 27, the formulation must first be prepared. Depending on the formulation 27, it may be necessary for stability reasons to prepare it only immediately before filling the primary packaging 20, as in the present embodiment.

[0189] To produce the formulation to be filled into the primary packaging 20 containing a pharmaceutical composition 27, in a first step S1, for example, the active ingredient (e.g., biologics), which may be available in bulk or as a lyophilisate, can be thawed under defined temperature conditions.

[0190] In a further step S2, a buffer solution can also be produced or prepared, if necessary, possibly by carrying out a filtration step.

[0191] In a further step S3, the respective composition can be produced by combining the components required for this purpose, in particular with the desired target concentration.

[0192] If necessary, sterilization and / or filtration can be carried out in a further step S4, especially with a defined filter size.

[0193] Once the formulation 27 has been produced, it can now be filled into a suitable primary packaging 20 in a further step S5 and the primary packaging can be closed with a closure component 30.

[0194] Step S5 comprises a sub-step S5A of providing a primary packaging material 20 to be filled, wherein the primary packaging material 20, for example a syringe 20, is provided in a predefined position and / or with a defined orientation relative to a position of a closure component 30 to be inserted into the primary packaging material 20, in particular along an insertion direction E of the closure component 30 and along a movement direction V of a closure device 200 for closing the primary packaging material 20 and in particular pre-filled with the composition 27, in particular in an associated system such as the filling system 1000.

[0195] The primary packaging material 20 can in particular be pre-filled with a formulation 27 which has been previously produced in steps S1 to S4 and has been introduced into the primary packaging material 20 in a further step, in particular with a defined quantity.

[0196] The primary packaging material 20 can be provided in the system for sealing in such a way that a longitudinal axis L of the receiving volume 23 of the primary packaging material 20 (see e.g. Fig. 3 and Fig 28 ) with a longitudinal axis of a closure component 30 to be inserted and / or the direction of movement V of the closure device 200. This can be achieved in a simple manner using a primary packaging holder according to the invention, for example with a primary packaging holder 100, 400, 400', 400", 400', 600 or 600' according to the invention.

[0197] If the primary packaging material 20 is filled, which is generally only possible after it has been placed in the primary packaging material holder, the closure component 30 can be set in a further step S5B, in particular by means of the closure device 200, and thereby the primary packaging material 20 can be closed, wherein the primary packaging material 20 is held by or received by a primary packaging material holder according to the present invention during the setting of the closure component 30 and the closure component 30 is placed in particular at a predefined position P along the longitudinal axis L of the receiving volume 23 within the receiving volume 23 of the primary packaging material 20.

[0198] If the primary packaging material 20 is filled and sealed with the closure component 30, an optional further step S6 can be carried out with a visual inspection, in particular with a 100% inspection to ensure that the closure component 30 has been placed correctly.

[0199] Subsequently, in a further step S7, the primary packaging material 20, filled with formulation 27 and sealed with closure component 30, can be labelled and packaged.

[0200] The aligned and / or correctly positioned provision of the primary packaging material 20 in step S5A may in particular include the following further sub-steps: Providing a primary packaging material 20 to be received, in particular for example a syringe, a cartridge or a vial, inserting the primary packaging material 20, preferably against resistance, into a primary packaging material holder according to the present invention, and optionally (if the primary packaging material 20 is not already aligned and / or correctly received in the primary packaging material holder) aligning and / or correctly positioning the primary packaging material 20 in the primary packaging material holder, wherein the alignment and / or positioning of the primary packaging material 20 is carried out by bringing the primary packaging material 20, during or after its insertion into the primary packaging material holder, into contact with the positioning contact surface 111 with a first section 24A of its outer surface and with the alignment contact surface of the primary packaging material holder with its second section 24B of its outer surface.

[0201] In particular, a step for aligning the primary packaging holder in the system can also be carried out once at the beginning and / or as required, in which the primary packaging holder is positioned and aligned relative to the closure device, in particular with a defined distance of the positioning contact surface 111 relative to a closure component 30 to be inserted or with a defined distance that is matched to a stroke of the setting piston 11 of the closure device, and in particular with the first positioning axis Z aligned to a direction of movement V of the closure device 200 or to a setting direction E of the closure component 30, wherein the primary packaging holder is in particular aligned in the system such that the positioning axis Z is aligned with the direction of movement V of the closure device 200 or with the setting direction E of the closure component 30.with the setting direction E of the locking component 30 and runs along a common straight line.

[0202] Fig. 30 Figure 1 shows a perspective view from an oblique angle of above, a section of a further embodiment of an arrangement 500" according to the invention, with a further embodiment of a guide rail 150" with four embodiments of primary packaging holders 700, 700', 700" (2x) mounted on the guide rail according to the present invention, wherein these primary packaging holders 700, 700', 700" are particularly similar to the primary packaging holder 400 described above, but have different bodies, in particular narrower bodies without the mounting recess 417 (cf. Figure 1). Fig. 24a) for the arrangement around the mounting pin 151 on the guide rail. The narrower bodies allow for a more space-saving arrangement and thus the arrangement of more primary packaging holders 700, 700', 700" along the guide rail 150" with a comparable length of the guide rail 150". Only corresponding mounting holes 153 for the fasteners 118A, 118B need to be provided in the guide rail 150". If the bodies of the primary packaging holders 700, 700', 700" are also adapted to the geometry of the guide rail 150" as in Fig. 30As shown, this results in a particularly space-saving arrangement. This allows the throughput of an associated filling system to be increased accordingly, because less distance needs to be covered between the sealing of two primary packaging units 20 and / or the transport device can be operated more slowly, which improves the accuracy when placing the primary packaging unit 20 in the longitudinal direction of the guide rail 150" and consequently, in some cases, allows the insertion of the primary packaging units 20 to be achieved with improved accuracy, especially without additional readjustment.

[0203] Fig. 31Figure 1 shows a perspective view from an oblique angle of a section of a further embodiment of an arrangement 500‴ according to the invention, with a further embodiment of a guide rail 150‴, in this case with eight embodiments of primary packaging holders 700 (2x), 700' (2x), 700" (4x) according to the present invention, each mounted on the guide rail 150‴, as shown in Figure 1. Fig. 30 are designed. The 500‴ arrangement differs essentially in length, positions and number of primary packaging holders: 700 (2x), 700' (2x), 700" (4x).

[0204] Fig. 32Figure 1 shows a perspective view from an oblique angle of a section of a further embodiment of an arrangement 500 iv< according to the invention, comprising a further embodiment of a guide rail 150 iv< and a further embodiment of a primary packaging holder 700‴ according to the present invention. This primary packaging holder 700‴ has a very wide body to which several pairs of retaining arms 113, 123 are attached. This primary packaging holder 700‴ is preferably also made in one piece from plastic. However, it can also be made in multiple parts, for example, in the manner of the primary packaging holder 100. The individual retaining arms 113, 123 need not be present in pairs. It is also possible for only the first retaining arm 113 to be present. Likewise, the retaining arms 113, 123 need not be attached to a linear or straight body.They can also extend, for example, in a star-shaped pattern in a radial direction from a (hollow) cylindrical body. What is advantageous depends in particular on the system configuration, especially on the existing transport and / or gripping devices as well as the closure and / or filling devices.

[0205] Fig. 33 shows the arrangement Fig. 31 in perspective view from obliquely below onto the underside of the arrangement 500‴.

[0206] Fig. 34 The figure shows, in a perspective view from an oblique angle above, a section of a further embodiment of an arrangement 500 v< according to the invention with the guide rail 150‴ from the Fig. 31 and 33, but with a further embodiment of primary packaging holders 800, 800' according to the present invention, wherein these primary packaging holders 800 and 800' are basically designed like the primary packaging holders 700 and 700' from the Figs. 30 and 31 , additionally, each has an insertion aid 801 or positioning aid 801 made of stainless steel on its upper side with a chamfered recess 802, which facilitates the insertion or placement of the closure component 30, wherein the insertion aids 801 or positioning aids 801 are each positioned at a distance above the positioning contact surface 111 (see Fig. 24a ) are arranged so that a primary packaging material 20 to be filled can still be inserted laterally into the primary packaging material holder 800, 800' and with a bottom side 25 of a rim 22 or flange 22 (cf. Fig. 3), which forms a first section 24A of the outer surface 24 of the primary packaging material 20, can be brought into contact with the positioning contact surface 111, in particular on this, for a defined positioning of the primary packaging material 20 along the positioning axis Z of the primary packaging material holder 800, 800'.

[0207] Fig. 35 Figure 1 shows a perspective view from an oblique angle of a further embodiment of an arrangement 500 vi< according to the invention with the guide rail 150‴ from the Fig. 31 , 33 and 34 , the primary packaging holders 800, 800' from Fig. 34 as well as further embodiments of primary packaging holders 800" according to the present invention, each of which, like the primary packaging holders 800, 800', has an insertion aid 801 or a positioning aid 801 for the closure component 30.

[0208] The primary packaging holders described in detail in this application each represent possible embodiments of a primary packaging holder according to the present invention. However, the design of such primary packaging holders is not limited to these embodiments. In particular, a primary packaging holder can also be designed to accommodate one or more other primary packaging materials, such as cartridges, vials, or the like, as described in particular in the description. Preferably, the basic principle of the primary packaging holder design is similar in each case. However, the design of the contact surfaces, against which the primary packaging material can be brought for correct positioning and alignment, can be different and, in particular, adapted to one or more primary packaging materials to be accommodated.Accordingly, the closure component 30 can also be a component other than a plug 30, for example a replaceable plug made of elastic material, lamellar plug, plug with external hook, plug with inner rod, plug with hook and inner rod, rolled edge plug, injection plug, impression plug and screw plug, each with or without Luer-Lock, closure caps, sealing caps, overcaps, combination plugs, Combi-Stopper closure cones, each with or without Luer-Lock. Further specifications for the VB are set out in the definitions. Abbreviations used

[0209] PKF Positioning contact surface AKF Alignment contact surface HA Holding arm PHP Primary packaging holder PM Primary packaging FS Guide rail VB Closure component VV Closure device Reference sign

[0210] 100, 400, 400', 400", 400", 600, 600', 700, 700', 700", 800, 800', 800" Exemplary embodiment of a primary packaging holder (PH) according to the invention 200 Exemplary embodiment of a closure device (VV) 500, 500', 500", 500‴, 500 iv< 500 v< , 500 vi< Exemplary embodiment of an arrangement according to the invention 1000 Exemplary embodiment of a system for (automated) closing of a primary packaging material (PM) with an exemplary embodiment of a PH according to the invention, in particular comprising a VV 11 Setting piston (punch) for setting a closure component (e.g. a stopper) 12 Vacuum chamber 13 Setting tube 13A Flange of the setting tube 13B Tubular section of the setting tube 14 Sealing device 14A Silicone cup 14B Insert 15 Hose 16, 17 Valve, in particular shut-off valve 18 Pressure gauge 19 Vacuum pump 20 Primary packaging (PM) 21 First opening of the receiving volume of the PM 22 Edge of the PM,especially flange 23 receiving volume of the PM 24 outer surface of the PM 24A first section of the outer surface of the PM 24B second section of the outer surface of the PM 25 underside of the partial surrounding rim (especially wing) 26 neck of a PM (e.g. in a vial or cartridge) 27 formulation containing a pharmaceutical composition 28 second opening of a PM 30 closure component (e.g. stopper) 40 air space between VB (e.g. stopper) and composition in a prefilled PM 110 receiving device 111 first positioning contact surface (PKF) 112 alignment contact surface (AKF) of the first retaining arm (HA) 113 first retaining arm (HA) 114 outer surface of the first HA 115A component (e.g. Y-clip), especially insert in the first HA, especially retaining / positioning element 115B component (e.g. Y-clip), especially insert in the first HA, especially Alignment element 116, 126 Fastening means, in particular screw,for fastening the insert (Y-clip) 117 through hole 118, 418 fastening means, in particular screw, for fastening the PH in a system, in particular on an FS 118A shaft 118B thread 119, 129 web of the retaining arm 122, 422 alignment contact surface (ACF) of the second retaining arm (HA) 123 second retaining arm (HA) 124 outer surface of the second HA 125A component (e.g. Y-clip), in particular insert in the second HA 125B component (e.g. Y-clip), in particular insert in the second HA, in particular alignment element 127 fastening sleeve 128 fastening hole 130 recess, in particular for lateral insertion of the PM 131, 141 clamping arm 132, 142, 143 range of motion for clamping arm 133 recess for anti-rotation device 134 fastening screw 135 mounting plate 136 Mounting hole 144 Through hole 145 Mounting hole 150, 150', Guide rail (FS) 150‴,150 iv< 151 Mounting pin 152 Mounting hole 153 Positioning mounting holes 154 Plastic sleeve 155 Alignment block 160 Gripper 170 Transport device 180 Alignment device 201 Holding and guiding device for the setting piston 300 Alignment device for adjusting the PH 310 Receiving block 320 Reference packaging gauge 415 Combined positioning and alignment element 416 Web 417 Recess for mounting pin 801 Insertion aid for the VB 802 Chamfered recess 803 Space for edge / flange of a PM A First system axis B Mounting axis d Thickness of the positioning element E Insertion direction of the VB,e.g., of a plug F Horizontal plane of the FS H1 Height of the web from an upper edge of the upper HA to a lower edge of the lower HA H2 Distance between the lower edge of the upper HA and the upper edge of the lower HA L Longitudinal axis of the receiving volume of the PM P Target position of the closure component in the receiving volume of the PM Q Quality defect regarding the insertion quality of the plug S1..S7 Process steps V Direction of movement of the system / closing device Z First positioning axis of the PH,

Claims

1. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") for receiving a primary packaging (20), wherein the primary packaging holder is designed to receive a primary packaging (20) having an outer surface (24) and a receiving volume (23) extending at least partially along a longitudinal axis (L) with at least one first opening (21), wherein the first opening (21) of the receiving volume (23) of the primary packaging (20) can be closed by means of a closure element (30) which can be inserted into the first opening (21) along the longitudinal axis (L) of the receiving volume (23), wherein the primary packaging holder is designed for arrangement in a system (1000) for closing the primary packaging material (10) is formed, wherein the primary packaging material holder has a first positioning axis (Z) and is designed tothe primary packaging material (20) is to be received in the primary packaging material holder with a defined position along the first positioning axis (Z) and with a defined orientation of the longitudinal axis (L) of the receiving volume (23) of the primary packaging material (20) relative to the first positioning axis (Z), wherein the primary packaging material holder has at least one receiving device (110) and the at least one receiving device (110) for receiving the primary packaging material (20) in the primary packaging material holder at the defined position along the first positioning axis has at least one first positioning contact surface (111) and for receiving the primary packaging material (20) with a defined orientation of the longitudinal axis (L) of the receiving volume (23) relative to the first positioning axis in the primary packaging material holder has at least one alignment contact surface (112, 422),wherein the first positioning contact surface (111) can be brought into contact with a first section (24A) of the outer surface of a primary packaging material to be received by the primary packaging material holder, in particular over a surface, and wherein the at least one alignment contact surface (112, 422) can be brought into contact with a second section (24B) of the outer surface of a primary packaging material (20) to be received by the primary packaging material holder, in particular over a surface.

2. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to claim 1, wherein the primary packaging holder is configured to receive the primary packaging (20) such that, in a state properly received by the primary packaging holder, it bears with at least one first section (24A) of its outer surface against the at least one first positioning contact surface (111) and simultaneously bears with at least one second section (24B) of its outer surface against the at least one alignment contact surface (112, 422).

3. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to claim 1 or 2, wherein the primary packaging holder is configured to receive the primary packaging (20) such that, in a state of the primary packaging being properly received by the primary packaging holder, the longitudinal axis (L) of the receiving volume (23) of the primary packaging (20) extends along the first positioning axis (Z) of the primary packaging holder.

4. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the primary packaging holder is designed to be positioned and aligned in a defined manner in a system (1000), in particular in a system comprising a closure device, such that in a properly installed state of the primary packaging holder in the system the first positioning axis (Z) of the primary packaging holder coincides with a first system axis (A, V), in particular is aligned with it.

5. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the receiving device (110) has at least one first holding arm (113) with an outer surface (114), wherein the first holding arm (113) extends at least partially in a direction perpendicular to the first positioning axis (Z) and a part of the outer surface (114) of the first holding arm (113) forms at least partially the first positioning contact surface (111).

6. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the part of the outer surface (114) of the first holding arm (113) which at least partially forms the first positioning contact surface (111) is formed by one or more sections of the outer surface (114) of the first holding arm (113) which extend in a plane perpendicular to the first positioning axis (Z), in particular by one or more sections of a top surface of the first holding arm (113).

7. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein at least one further section of the outer surface (114) of the first holding arm (113) forms at least partially the at least one alignment contact surface (112, 422).

8. Primary packaging holder (100, 600, 600') according to one of the preceding claims, wherein the receiving device (110) has one or more holding arms, wherein in particular a first holding arm (113) has at least one first component (115A) designed separately and as a positioning element, wherein the first component in particular forms a first holding element or a part thereof, wherein a section of the outer surface of the positioning element (115A) forms at least partially the first positioning contact surface (111), wherein the positioning element (115A) is in particular arranged in the receiving device (110) such that the section of the outer surface of the positioning element (115A) which forms at least partially the first positioning contact surface (111) extends in a plane perpendicular to the first positioning axis (Z).

9. Primary packaging holder (100, 600, 600') according to one of the preceding claims, wherein the receiving device (110) has one or more holding arms (113, 123), wherein in particular at least one holding arm (113, 123), in the case of several holding arms preferably at least one second holding arm (123), has at least one second component (115B) designed separately and as an alignment element, wherein a section of the outer surface of the alignment element forms at least partially the at least one alignment contact surface (112, 422), wherein the alignment element is in particular arranged in the receiving device (110) such that the section of the outer surface of the alignment element which forms at least partially the alignment contact surface (112, 422) extends in a direction parallel to the first positioning axis.

10. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the section of the outer surface of the alignment element, which at least partially forms the at least one alignment contact surface (112, 422), is / forms a contact surface, in particular for the second section (24B) of the outer surface of the primary packaging (20), for the defined alignment of the longitudinal axis (L) of the receiving volume (23) of the primary packaging (20) relative to the first positioning axis.

11. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the primary packaging holder is designed such that a position of the first positioning contact surface (111) along the first positioning axis (Z) can be defined, in particular adjusted, via a thickness (d) of the positioning element (115A), and thus in particular the predefined position along the first positioning axis (Z) with which the primary packaging (20) can be received by the primary packaging holder.

12. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the primary packaging holder is configured to receive a primary packaging (20) having a rim (22) that at least partially surrounds the first opening (21) and projects (radially) outwards with respect to the longitudinal axis (L) of the receiving volume (23) of the primary packaging (20), with at least one underside (25) extending in a direction, in particular a plane, perpendicular to the longitudinal axis (L) of the receiving volume (23), wherein the underside of the projecting rim (22) forms in particular the first section (24A) of the outer surface of the primary packaging with which the first positioning contact surface (111) Contact can be made at / will be made at the defined positioning of the primary packaging (20) in the primary packaging holder.

13. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the primary packaging holder is configured to receive a primary packaging (20) whose outer surface has at least one section with a lateral surface extending parallel to the longitudinal axis (L) of the primary packaging (20), such that the lateral surface of the primary packaging (20), when the primary packaging (20) is properly received by the primary packaging holder, rests against the alignment contact surface (112, 422).

14. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to any of the preceding claims, wherein the primary packaging holder is configured to accommodate a primary packaging (20) selected from a group comprising: pharmaceutical primary packaging, cosmetic primary packaging or food containers, wherein the group of pharmaceutical primary packaging includes syringe bodies, vials, cartridges and carpules.

15. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the at least one alignment element is configured to receive a primary packaging element such that the primary packaging element bears against the at least one alignment element with at least one contact surface, in particular with a part of its outer surface, in particular against its alignment contact surface (112, 422), wherein the alignment element is in particular configured such that, when the primary packaging element bears against the alignment element with its outer surface, in particular against its alignment contact surface, in a state of the primary packaging holder installed in a system (1000) with a closure device (200),the longitudinal axis (L) of the receiving volume (23) of the primary packaging (20) is aligned with the first system axis (A) and / or a longitudinal axis (L) of a closure component (30) to be inserted into the primary packaging (20) and / or with an insertion direction (E) of the closure component (30) and / or with a movement direction (V) of the closure device (200).

16. Primary packaging holder (100, 400, 400", 600, 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the primary packaging holder has at least one alignment element (115B, 125B, 416) and / or at least one retaining element (115A, 125A), wherein in the case of at least two elements, preferably a first alignment element (115B, 416) is arranged below the first positioning contact surface (111), and in particular a second alignment element (125B) and / or retaining element (125A) is arranged below the first alignment element (115B, 416) and spaced apart along the positioning axis (Z) from the first alignment element (115B), wherein the primary packaging holder is in particular designed to is to hold a primary packaging material (20) in such a way that, in a state held by the primary packaging material holder, one or more contact surfaces (24A, 24B) of the primary packaging material (20) are in contact with the at least one alignment element (115B, 125B,416) and / or the at least one retaining element (115A, 125A).

17. Primary packaging holder (400, 400', 400", 400‴,) according to one of claims 8 to 16, wherein the primary packaging holder has a contact surface (416, 422) extending downwards from the first holding arm (113) and parallel to the first positioning axis (Z), in particular a web (416, 422) which is configured to support a received primary packaging (20) in the aligned position.

18. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to any one of the preceding claims, wherein the primary packaging holder is mounted on a guide rail (150, 150', 150", 150‴, 150 iv) is mountable, in particular such that the primary packaging holder in an installed state (on the guide rail in a (filling) system) is alignable with its first positioning axis (Z) in a horizontal plane (F) and relative to the first system axis (A), preferably to an insertion direction (E) of a closure component (30) and / or relative to a movement direction (V) of a closure device (200), and in particular by means of at least one, preferably two, fastening means (118, 418) on the guide rail (150, 150', 150", 150‴, 150 iv ) can be fixed.

19. Primary packaging holder (100, 400, 400', 400", 400‴, 600, 600', 700, 700', 700", 800, 800', 800") according to one of the preceding claims, wherein the primary packaging holder has at least one, preferably two, through holes (117) extending through the primary packaging holder, which in particular extend parallel to the positioning axis (Z) of the primary packaging holder, wherein the at least one through hole is in particular configured such that the primary packaging holder can be fastened to a guide rail (150, 150', 150", 150‴, 150 iv ) suitable fastening means through which at least one through hole can be passed, in particular to mount the primary packaging holder in an arrangement with a guide rail (150, 150', 150", 150', 150 iv) to connect, and, wherein the primary packaging holder, in particular in an arrangement, can be aligned and in particular fixed in and / or on the guide rail by means of the through holes, in particular in conjunction with one, preferably with two, fastening means (118, 418), in a state of the guide rail (150, 150', 150", 150‴, 150 iv ) especially relative to a first plant axis (A).

20. Arrangement (500, 500', 500", 500‴, 500 iv , 500 v , 500 vi ) comprising: - a guide rail (150, 150', 150", 150‴, 150 iv), wherein the guide rail is designed for use in a filling plant and / or in a plant for the (automated) sealing of a primary packaging material and the guide rail is designed in particular to accommodate at least one primary packaging material holder according to one of claims 1 to 19, and - at least one or more primary packaging material holders according to one of claims 1 to 19, wherein the guide rail (150, 150', 150", 150‴, 150 iv ) preferably designed to accommodate two or more primary packaging holders, preferably to accommodate eight primary packaging holders, and wherein the at least one primary packaging holder is mounted on the guide rail (150, 150', 150", 150‴, 150 iv ) is mountable or is mounted, preferably with at least one, preferably with at least two fasteners (118, 418).

21. Arrangement (500, 500', 500", 500‴, 500 iv , 500 v , 500 vi) according to claim 20, further comprising: - at least one closure device (200), preferably a closure device (200) comprising a setting tube (11), wherein the setting tube is arranged in particular above the at least one primary packaging holder, preferably in a state of the arrangement installed in a system for (automated) closing a primary packaging, - optionally at least one primary packaging (20) which is received by the at least one primary packaging holder, wherein at least one primary packaging with a predefined orientation and / or orientation in space can be received and in particular held at least temporarily by means of the arrangement, in particular for closing the primary packaging,wherein the primary packaging material can be held in a predefined position and / or with a defined orientation relative to a position of a closure component (30) to be inserted into the primary packaging material along an insertion direction (E) of the closure component (30) and a movement direction (V) of the closure device (200).

22. Method for closing a primary packaging (20), wherein the primary packaging (20) has an outer surface and a receiving volume (23) extending at least partially along a longitudinal axis (L) with at least one first opening, wherein the first opening (21) of the receiving volume (23) of the primary packaging (20) is furthermore, in particular, closable by means of a closure component (30) which can be inserted into the first opening (21) for closing the primary packaging (20) along the longitudinal axis (L) of the receiving volume (23), wherein the primary packaging is preferably prefilled with a formulation containing a composition (27),comprising at least the following steps: - providing a primary packaging material, preferably pre-filled, oriented in a predefined position and / or with a defined orientation relative to a position of a closure component (30) to be inserted into the primary packaging material along an insertion direction (E) of the closure component (30) and along a movement direction (V) of a closure device (200) for closing the primary packaging material, in particular in a system (filling system), preferably oriented such that a longitudinal axis (L) of the receiving volume (23) of the primary packaging material is aligned with the longitudinal axis (L) of the closure component (30) and / or the movement direction (V) of the closure device (200), and - placing the closure component (30), in particular by means of a closure device (200), wherein the primary packaging material is held by a primary packaging material holder during the placing of the closure component,which is designed according to one of claims 1 to 19, or from a primary packaging holder which is part of an arrangement according to one of claims 20 or 21, wherein the closure component (30) is placed in particular at a predefined position along the longitudinal axis (L) of the receiving volume (23) within the receiving volume (23) of the primary packaging.

23. Method for closing a primary packaging material (20) according to claim 22, wherein the placement of the closure component (30) is carried out under vacuum, in particular by inserting a stopper, in particular by means of a vacuum chamber (12), especially if the primary packaging material is a syringe body.

24. Method for closing a primary packaging (20) according to claim 22 or 23, wherein the insertion of the closure component (30) is carried out in an insertion direction (E) along a movement direction (V) of the closure device (200) and aligned with the first positioning axis of the PH, in particular such that, especially if the primary packaging is a syringe body, the closure component (30) is located at a predefined position in the receiving volume (23) of the primary packaging after insertion and closes the primary packaging.

25. Method for closing a primary packaging material according to one of claims 22 to 24, wherein the closure component (30) is placed in the receiving volume (23) of the primary packaging material such that, after insertion, it is located at a predefined position above a composition filled into the primary packaging material with which the primary packaging material is in particular prefilled, wherein the closure component (30), in particular a stopper, is preferably inserted into the primary packaging material such that it does not come into contact with the prefilled composition at the predefined position and in particular a predefined air space is formed between the prefilled composition and the inserted closure component (30).

26. Method for sealing a primary packaging material (20) according to claims 22 to 25, wherein the primary packaging material (20) is a syringe body, preferably a pre-filled syringe, more preferably a 0.5 ml Terumo ®The syringe is, and the closure component (30) is a stopper.

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