The transport simulation included components such as a holding device and multiple containers with particle loads.

Abstract

The present invention relates to an assembly comprising: a) a holding device including a plurality of holding elements, and b) a plurality of containers; wherein each container includes a container wall at least partially surrounding the interior of the container; wherein the container wall has an outer surface facing away from the interior of the container; wherein each container is detachably held by at least one holding element through contact between at least one of the holding elements and the outer surface of the container wall of the respective container; wherein, immediately following a transport simulation of the assembly, the number of particles with a diameter of at least 5 μm on the outer surface of the containers does not exceed 2.7 particles per square centimeter of the sum of the surface areas of the outer surfaces of all containers; wherein the transport simulation consists of a rotating plane drop test and a random vibration test performed sequentially.

Description

Technical Field

[0001] This invention relates to a component, the component comprising

[0002] a) A retaining device, said retaining device comprising a plurality of retaining elements, and

[0003] b) Multiple containers;

[0004] Each container includes a container wall that at least partially surrounds the interior of the container; wherein the container wall has an outer surface facing away from the interior of the container; wherein each container is detachably held by at least one retaining element through contact between at least one of the retaining elements and the outer surface of the container wall of the respective container; wherein, immediately following a transport simulation of the assembly, the number of particles with a diameter of at least 5 μm on the outer surface of the containers in the plurality of containers does not exceed 2.7 particles per square centimeter of the total surface area of ​​the outer surfaces of all the containers in the plurality of containers, wherein the transport simulation consists of a rotating plane drop test and a random vibration test performed sequentially. Furthermore, the present invention relates to a method for preparing the assembly; a method comprising filling at least a portion of a container with a pharmaceutical composition or a cosmetic composition or both; a method comprising performing a transport simulation of the assembly and determining the number of particles; and the use of the assembly and a filling machine. Background Technology

[0005] Containers made of glass, and later of polymers, have long been used for the safe transport of fluids and powders. Over the past few decades, the techniques for transporting fluids and powders using glass and polymer containers have become increasingly diverse and complex. One such technique is the subject of this application: pharmaceutical packaging. In the pharmaceutical industry, containers (such as vials, syringes, ampoules, and cartridges) serve as primary packaging for a wide variety of pharmaceutically related compositions (particularly drugs, such as vaccines) and cosmetic compositions (particularly cosmetic compositions injected into the skin).

[0006] When manufacturing containers for pharmaceutical or cosmetic applications, a so-called nesting scheme is now generally preferred, where a retaining structure (also called a nesting element) is applied to hold or support multiple containers simultaneously in a given configuration. These nesting elements are typically packaged in transport or packaging containers (also called basins) and shipped to customers, such as pharmaceutical companies or filling machines. For further processing of the containers, the basin is opened. Further processing of the containers typically involves the following automated steps: removing the container from the basin; filling the container with a composition (e.g., a pharmaceutical or cosmetic composition); sealing the pre-filled container, for example, using a hypodermic needle via a Luer connector in the case of a syringe; and vacuum-packing the individual containers in foil bags for retail. Each of these steps carries a risk of failure, such as processing malfunctions, syringe / needle connection failures, foil bag damage, etc. Summary of the Invention

[0007] Generally speaking, the purpose of this invention is to overcome, at least in part, the disadvantages caused by the prior art.

[0008] Another object of the present invention is to provide an assembly of nested multiple pharmaceutical or cosmetic packaging containers, the assembly enabling further handling of the containers with fewer handling failures after transportation and storage. According to another object of the present invention, an assembly of nested multiple pharmaceutical or cosmetic packaging containers is provided, the assembly enabling reduced discharge failures after transportation and storage of the assembly and subsequent filling and sealing of the containers. Furthermore, an object of the present invention is to provide an assembly of nested multiple pharmaceutical or cosmetic packaging containers, the assembly enabling less damage to vacuum foil pouch packaging after transportation and storage of the assembly. Another object of the present invention is to provide a method for distinguishing components that address one or more of the above-mentioned problems from components not used for quality control.

[0009] The independent claims contribute to at least partially achieving at least one, and preferably more than one, of the above objectives. The dependent claims provide preferred embodiments that help to at least partially achieve at least one objective.

[0010] The contribution to solving at least one of the objectives of the present invention is made by embodiment 1 of the component, which includes

[0011] a) A retaining device, said retaining device comprising a plurality of retaining elements, and

[0012] b) Multiple containers;

[0013] Each of the plurality of containers includes a container wall that at least partially surrounds the interior of the container; the container wall has an outer surface facing away from the interior of the container; each of the plurality of containers is detachably held by at least one of the holding elements in contact with the outer surface of the container wall of the corresponding container in the plurality of containers; wherein, immediately following a transport simulation of the assembly, the number of particles with a diameter of at least 5 μm on the outer surface of the containers in the plurality of containers does not exceed, in any case, 2.7 particles per square centimeter, preferably 2.6 particles, more preferably 2.5 particles, more preferably 2.4 particles, more preferably 2.3 particles, more preferably 2.2 particles, more preferably 2.1 particles, more preferably 2.0 particles, more preferably 1.9 particles, more preferably 1.8 particles, more preferably 1.7 particles, even more preferably 1.6 particles, and most preferably 1.5 particles; wherein the transport simulation consists of a rotating plane drop test and a random vibration test performed sequentially. The transportation simulation is described in more detail in the Test Methods section below.

[0014] In Embodiment 2 of the component according to the invention, the component is designed according to Embodiment 1, wherein, immediately following a transport simulation of the component, the number of particles with a diameter of at least 2 μm on the outer surface of the containers in the plurality of containers does not exceed, in each case, 8.7 particles per square centimeter, preferably 8.5 particles, more preferably 8.3 particles, more preferably 8.1 particles, more preferably 7.9 particles, more preferably 7.7 particles, more preferably 7.5 particles, more preferably 7.3 particles, more preferably 7.1 particles, more preferably 6.9 particles, more preferably 6.7 particles, more preferably 6.5 particles, more preferably 6.3 particles, more preferably 6.1 particles, more preferably 5.9 particles, more preferably 5.7 particles, more preferably 5.5 particles, more preferably 5.3 particles, more preferably 5.1 particles, more preferably 4.9 particles, even more preferably 4.7 particles, and most preferably 4.5 particles.

[0015] In embodiment 3 of the component according to the invention, the component is designed according to embodiment 1 or 2, wherein the plurality of containers consists of 4 to 500, preferably 9 to 400, more preferably 12 to 300, more preferably 16 to 200, more preferably 16 to 160, more preferably 16 to 100, more preferably 16 to 90, more preferably 16 to 80, more preferably 16 to 70, even more preferably 16 to 60, and most preferably 16 to 50 containers.

[0016] In embodiment 4 of the component according to the invention, the component is designed according to any one of embodiments 1 to 3, wherein the retaining device includes at least one base; wherein the at least one base includes the retaining element, or the retaining element of the plurality of retaining elements is arranged at the at least one base.

[0017] In embodiment 5 of the component according to the invention, the component is designed according to embodiment 4, wherein the at least one substrate includes a plurality of holes in a first surface; wherein each of the plurality of containers extends at least through the first surface into one of the plurality of holes. Preferably, the first surface extends in both the width and length directions of the substrate.

[0018] In embodiment 6 of the component according to the invention, the component is designed according to embodiment 5, wherein the at least one substrate includes another surface opposite to the first surface; wherein each of the plurality of holes extends from the first surface to the other surface. Preferably, the other surface extends in the width and length directions of the substrate.

[0019] In embodiment 7 of the component according to the invention, the component is designed according to embodiment 5 or 6, wherein each retaining element of the retaining element includes at least one of the plurality of holes, or the retaining element is different from the holes of the plurality of holes.

[0020] In embodiment 8 of the component according to the invention, the component is designed according to any of the foregoing embodiments, wherein each of the plurality of containers is preferably held non-destructively and removably by at least one retaining element in a positive fit or friction fit, or a combination of both, with the outer surface of the container wall of the corresponding container of the plurality of containers. The container is non-destructively and removably held by one or more retaining elements if the container can be removed from the retaining device without damaging the container and preferably without damaging the retaining device. A preferred positive fit is a positive fit with a first end or another end of the container, or both. Preferably, the retaining elements are designed and arranged such that establishing the positive fit involves elastically deforming the corresponding one or more retaining elements. Here, once the positive fit is established or not established, the one or more retaining elements can maintain elastic deformation.

[0021] In embodiment 9 of the component according to the invention, the component is designed according to embodiment 8, wherein under the action of a force twice the weight of the empty container applied to the container in one direction, the form fit or friction fit or a combination of both prevents, in each case, any movement of the container in this direction from exceeding 5%, preferably more than 3%, more preferably more than 1% of the range of the container along this direction.

[0022] In embodiment 10 of the component according to the invention, the component is designed according to any one of embodiments 4 to 9, wherein the at least one substrate is at least partially, preferably entirely, plate-shaped.

[0023] In embodiment 11 of the component according to the invention, the component is a design according to any of embodiments 4 to 10, wherein the first surface is a flat surface. Alternatively, preferably, the other surface is a flat surface. Preferably, the first surface and the other surface are planar parallel to each other.

[0024] In embodiment 12 of the component according to the invention, the component is designed according to any of the foregoing embodiments therein, wherein the component further includes a preferably closed packaging container; wherein the packaging container includes a packaging container wall, preferably composed of a packaging container wall, the packaging container wall at least partially surrounding the interior of the packaging container; wherein the retaining device and the container are arranged inside the packaging container.

[0025] In embodiment 13 of the component according to the invention, the component is designed according to embodiment 12, wherein the packaging container is closed by a lid joined to the packaging container. Preferably, the lid is a multi-layered sheet. Alternatively, preferably, the lid is breathable.

[0026] In embodiment 14 of the component according to the invention, the component is designed according to embodiment 12 or 13, wherein the packaging container wall comprises a packaging container polymer, preferably composed of a packaging container polymer.

[0027] In embodiment 15 of the component according to the invention, the component is designed according to embodiment 14, wherein the packaging container polymer is selected from the group consisting of: condensation polymers, preferably polyethylene terephthalate; polyacrylates, preferably polymethyl methacrylate; and polyolefins, preferably polypropylene or polyethylene; or combinations of at least two of these.

[0028] In embodiment 16 of the component according to the invention, the component is designed according to any of embodiments 12 to 15, wherein the component further includes a preferably closed outer packaging, wherein the packaging container is arranged within the outer packaging. The preferred outer packaging is a pouch, preferably made of plastic film. Alternatively, preferably, the outer packaging provides a barrier against the permeation of inert gases. Alternatively, preferably, the outer packaging is hermetically sealed. Alternatively, preferably, the outer packaging is less permeable to inert gases than the cap. Particularly preferably, the outer packaging provides a barrier against the permeation of inert gases, while the cap is permeable to inert gases.

[0029] In embodiment 17 of the component according to the invention, the component is designed according to embodiment 16, wherein the outer packaging includes an atmosphere, and in each case, based on the volume of the atmosphere, the proportion of inert gas included in the atmosphere is at least 50% by volume, preferably at least 60% by volume, preferably at least 70% by volume, more preferably at least 80% by volume, even more preferably at least 90% by volume, and most preferably at least 95% by volume.

[0030] In embodiment 18 of the component according to the invention, the component is designed according to any of the foregoing embodiments therein, wherein the container has been purified, preferably sterilized. Preferably, the component has been purified, preferably sterilized. In the context of this application, purification is defined as a broad term encompassing the reduction of the number of microorganisms and biological agents, such as fungi, bacteria, viruses, spore forms, prions, single-celled eukaryotes, etc. The specific terms disinfection and sterilization differ in the amount of these microorganisms and biological agents reduced. Disinfection can only reduce the number of said contaminants, but sterilization can effectively kill, inactivate, or eliminate all forms of life and other biological agents present, i.e., a reduction of 100%. Therefore, disinfection is less effective than sterilization.

[0031] In embodiment 19 of the component according to the invention, the component is according to any of the designs in the foregoing embodiments, wherein the container among the plurality of containers is a packaging container for pharmaceutical or cosmetic packaging, or both. Preferably, the container among the plurality of containers is a primary packaging container for a pharmaceutical composition or cosmetic composition, or both. A preferred pharmaceutical composition is a liquid. A preferred cosmetic composition is a liquid. Preferably, the container among the plurality of containers is suitable for packaging parenteral medicines according to section 3.2.1 of the 7th edition of the European Pharmacopoeia 2011.

[0032] In embodiment 20 of the component according to the invention, the component is a design according to any of the foregoing embodiments thereof, wherein each of the plurality of containers comprises, preferably from top to bottom, in the following order:

[0033] a. A first end portion, the first end portion including a discharge port.

[0034] b. Main body, and

[0035] c. The other end.

[0036] In embodiment 21 of the component according to the invention, the component is designed according to embodiment 20, wherein the main body is cylindrical. In the case of a syringe, the cylindrical main body is generally referred to as a barrel.

[0037] In embodiment 22 of the component according to the invention, the component is designed according to embodiment 20 or 21, wherein the other end is an upright base, or includes another hole, or both. A preferred container with an upright base at the other end is a vial or cartridge. A preferred container with another hole at the other end is a syringe. Preferably, the area of ​​the discharge port of the container is smaller than the area of ​​another hole in the same container. The preferred other hole is designed to receive a plunger.

[0038] In embodiment 23 of the component according to the invention, the component is designed according to embodiment 22, wherein, for each of the plurality of containers, the area of ​​the other hole is greater than the area of ​​the discharge hole.

[0039] In embodiment 24 of the component according to the invention, the component is designed according to embodiment 22 or 23, wherein the other end further includes an edge that laterally protrudes beyond the body portion and at least partially, preferably completely surrounds the other hole.

[0040] In embodiment 25 of the component according to the invention, the component is designed according to any of embodiments 20 to 24, wherein the other end of one of the plurality of containers faces the bottom of the packaging container, also referred to herein as the bottom of the packaging container.

[0041] In embodiment 26 of the component according to the invention, the component is designed according to any of embodiments 20 to 25, wherein, for each of the plurality of containers, the first end includes a connecting element; wherein the connecting element includes threads for connecting an auxiliary component to a corresponding container among the plurality of containers. A preferred auxiliary component is selected from the group consisting of a needle, a nozzle, and a tube, or a combination of at least two of these. A preferred needle is a hypodermic needle.

[0042] In embodiment 27 of the component according to the invention, the component is designed according to any of embodiments 20 to 26, wherein, for each of the plurality of containers, the first end includes a protrusion of a tapered fitting. A preferred tapered fitting is a Luer connector. Typically, a Luer connector may or may not include threads.

[0043] In embodiment 28 of the component according to the invention, the component is designed according to embodiment 27, wherein the protrusion of the tapered fitting includes threads. Preferably, the threads are arranged in a sleeve.

[0044] In embodiment 29 of the component according to the invention, the component is designed according to any of embodiments 20 to 28, wherein, for each container, in relation to the entire body portion, in each case, the thickness of the container wall is within the range of the average value of the container wall thickness in the body portion of the respective container among the plurality of containers, ±0.3 mm, preferably ±0.2 mm, more preferably ±0.15 mm, more preferably ±0.1 mm, and most preferably ±0.08 mm.

[0045] In embodiment 30 of the component according to the invention, the component is designed according to any of embodiments 20 to 29, wherein, for each of the plurality of containers, the thickness of the container wall, over the entire body portion, is in the range of 0.2 to 3 mm, preferably 0.3 to 2.5 mm, more preferably 0.4 to 2.2 mm. In a preferred embodiment, for each primary packaging container, the thickness of the container wall, over the entire body portion, is in the range of 1.0 to 1.1 mm. In another preferred embodiment, for each primary packaging container, the thickness of the container wall, over the entire body portion, is in the range of 1.4 to 1.8 mm. In yet another preferred embodiment, for each primary packaging container, the thickness of the container wall, over the entire body portion, is in the range of 0.6 to 2.0 mm.

[0046] In embodiment 31 of the component according to the invention, the component is designed according to any of the foregoing embodiments therein, wherein, for each of the plurality of containers, the internal volume of the container is in the range of 0.5 to 100 ml, preferably 1 to 100 ml, more preferably 1 to 50 ml, even more preferably 1 to 10 ml, and most preferably 2 to 10 ml.

[0047] In embodiment 32 of the component according to the invention, the component is designed according to any of the foregoing embodiments, wherein the container among the plurality of containers is selected from the group consisting of vials, syringes, cartridges, and ampoules, or a combination of at least two of them. A preferred cartridge is designed to serve as a reservoir in a medical component (preferably a portable medical component). A preferred portable medical device is an insulin pump.

[0048] In embodiment 33 of the component according to the invention, the component is designed according to any of the foregoing embodiments therein, wherein, for each of the plurality of containers, the container wall comprises glass or a polymer or both, preferably composed of glass or a polymer or both. Here, polymer is particularly preferred.

[0049] In embodiment 34 of the component according to the invention, the component is designed according to embodiment 33, wherein the polymer is a cyclic olefin copolymer or a cyclic olefin polymer, or a mixture thereof.

[0050] In embodiment 35 of the component according to the invention, the component is designed according to embodiment 33 or 34, wherein the type of glass is selected from the group consisting of: borosilicate glass (preferably type I glass); aluminosilicate glass; and fused silica; or a combination of at least two of these.

[0051] In embodiment 36 of the component according to the invention, the component is designed according to any of embodiments 33 to 35, wherein in each case, based on the weight of the glass, the glass has a total content of alkali metal atoms and alkali metal ions of at least 1% by weight, preferably at least 2% by weight, more preferably at least 3% by weight, even more preferably at least 4% by weight, and most preferably at least 5% by weight. Typically, in each case, based on the weight of the glass, the total content of alkali metal atoms and alkali metal ions does not exceed 20% by weight, preferably not more than 15% by weight.

[0052] The contribution to solving at least one object of the present invention is made by embodiment 1 of a method 1 for preparing components of the present invention according to any embodiment of the present invention, the method comprising the following method steps.

[0053] A) Provide

[0054] I) the holding device, and

[0055] II) The plurality of containers;

[0056] B) The retaining device is loaded with containers from a plurality of containers such that each of the plurality of containers is preferably nondestructively and removably retained by at least one retaining element through contact with the outer surface of the container wall of the corresponding container in the plurality of containers by at least one of the retaining elements.

[0057] In embodiment 2 of method 1 according to the present invention, this method is designed according to embodiment 1, wherein the method includes the following further method steps.

[0058] C) Place the container holding device with multiple containers into the packaging container, and

[0059] D) Seal the packaging container.

[0060] In embodiment 3 of method 1 according to the invention, this method is designed according to embodiment 2, wherein step D) of the method includes joining a cap to the packaging container. The preferred cap is a sheet. The preferred sheet is a multilayer sheet. The preferred cap is permeable to inert gases. Preferably, the joining is achieved by gluing or sealing the cap to the packaging container. In the case of sealing, the joining is formed by a liquid and its solidification. Hot melt adhesive can be used here. In the case of gluing, the chemical bonds that create the joining are formed between the interface or surfaces of the two items to be joined.

[0061] In embodiment 4 of method 1 according to the present invention, this method is designed according to embodiment 2 or 3 thereof, wherein the method includes the following further method steps.

[0062] E) Place the packaging container with retaining device and multiple containers into the outer packaging, and

[0063] F) Seal the outer packaging.

[0064] The preferred outer packaging is a small bag, preferably made of plastic film. The preferred method step F) includes sealing the outer packaging. The preferred outer packaging provides a barrier against the penetration of inert gases. The preferred outer packaging is airtight.

[0065] In embodiment 5 of method 1 according to the invention, this method is designed according to embodiment 4, wherein the atmosphere in the outer packaging is conditioned prior to method step F). Preferably, conditioned atmosphere in the outer packaging includes introducing an inert gas into the outer packaging. Preferably, the outer packaging is less permeable to inert gases than the lid. Particularly preferably, the outer packaging provides a barrier against inert gas penetration, while the lid is permeable to inert gases.

[0066] In embodiment 6 of method 1 according to the invention, this method is based on any of the designs in the foregoing embodiments, wherein after method step B), the method includes another method step, which includes processing at least a portion of the outer surface of at least a portion of the container (preferably each of the plurality of containers). Preferably, the processing is performed before method step D), more preferably before method step C).

[0067] In embodiment 7 of method 1 according to the present invention, this method is designed according to embodiment 6 thereof, wherein the process includes freeze drying.

[0068] The contribution to solving at least one of the objectives of the present invention is made by embodiment 1 of method 2, which includes the following method steps.

[0069] A. Providing any of the components of the present invention according to any embodiment of the present invention;

[0070] B. Containers, preferably all of them, filled with a pharmaceutical composition or a cosmetic composition or both.

[0071] In embodiment 2 of the method 2 according to the present invention, this method is designed according to embodiment 1, wherein the packaging container is opened before method step B.

[0072] In embodiment 3 of method 2 according to the invention, this method is designed according to embodiment 1 or 2, wherein the retaining device is removed from the packaging container before method step B.

[0073] In embodiment 4 of method 2 according to the invention, this method is based on any of the designs in the foregoing embodiments thereof, wherein, in method step B, at least a portion of the container is held by a holding device.

[0074] In embodiment 5 of method 2 according to the invention, this method is based on any of the designs in the foregoing embodiments thereof, wherein, in method step B, each of the at least portions of the containers is filled via its discharge port.

[0075] In embodiment 6 of method 2 according to the invention, this method is based on any of the designs in the foregoing embodiments thereof, wherein, prior to method step B, the outer packaging is opened and the packaging container is removed from the outer packaging.

[0076] In embodiment 7 of method 2 according to the invention, this method is based on any of the designs in the foregoing embodiments thereof, wherein the method is a method of filling at least a portion of the containers with a pharmaceutical composition or a cosmetic composition or both.

[0077] In embodiment 8 of method 2 according to the present invention, this method is designed according to any of the foregoing embodiments thereof, wherein in method step B, at least one filled container is obtained, wherein the method further includes the following method steps

[0078] C. The auxiliary portion is preferably connected to the at least one filled container via a tapered fitting or via threads or both.

[0079] The preferred auxiliary component is selected from one of the group consisting of a needle, a nozzle, and a tube, or a combination of at least two of them. The preferred needle is a hypodermal injection needle.

[0080] The contribution to solving at least one of the objectives of the present invention is made by embodiment 1 of method 3, which includes the following method steps.

[0081] A] Provides components, the components including

[0082] I] A holding device, the holding device comprising a plurality of holding elements, and

[0083] II] Multiple containers,

[0084] Each of the plurality of containers includes a container wall that at least partially surrounds the interior of the container.

[0085] The container wall has an outer surface facing away from the interior of the container.

[0086] Each of the plurality of containers is preferably held nondestructively and detachably by at least one retaining element in contact with the outer surface of the container wall of the respective container of the plurality of containers;

[0087] B] Perform transportation simulation on the components;

[0088] C] For at least some, preferably all, of the plurality of containers, determine whether the number of particles on the outer surface of the container wall of at least some of the containers exceeds a threshold; and

[0089] D] If

[0090] If the number of particles exceeds the threshold, discard the container.

[0091] II] The number of particles is not higher than the threshold: the container is filled with a pharmaceutical composition or a cosmetic composition or both.

[0092] As part of the transportation simulation of method step B], any exposure to mechanical stress or deviations from an ambient temperature of 23°C, an ambient air pressure of 100 kPa (0.986 atm), or a relative atmospheric humidity of 50% as deemed appropriate by those skilled in the art in the context of this invention are taken into consideration. Preferred mechanical stress is one selected from the group consisting of vibration, drop, impact, and weight load (preferably from above), or a combination of at least two of these. Preferred transportation simulation includes simulations selected from the group consisting of: manual handling; mechanical handling; stacking; rail transport; environmental hazards (preferably temperature shock or increased humidity or both); low ambient pressure or high altitude hazards; or a combination of at least two of these. Preferred method 3 is a method of filling at least a portion of a container with a pharmaceutical composition or a cosmetic composition or both. Preferred containers among a plurality of containers are those specified in one embodiment of the component of the invention. Here, the holding element of the holding device can be any design deemed appropriate by those skilled in the art. In particular, the design of the holding element is not limited to the holding element described in the context of the component of the invention. Preferably, the holding device has one or more features of a holding device of the component of the invention according to any embodiment of the invention. However, in the context of Method 3 of the present invention, the holding device is not limited to the embodiments of the components. Rather, preferably, in steps B] to D] of the method, it is tested whether the component provided in step A] is a component according to the present invention. Therefore, preferably, Method 3 provides a method for separating the components of the present invention from those components that do not conform to the present invention. In this sense, preferably, Method 3 is a method for providing components according to the present invention. Therefore, Method 3 has the same inventive concept as the components of the present invention.

[0093] The preferred threshold is the number of particles with a diameter of at least 5 μm, in each case being 2.7 particles per square centimeter of the total surface area of ​​the outer surface of the container walls of at least a portion of the containers in the plurality of containers, preferably 2.6 particles, more preferably 2.5 particles, more preferably 2.4 particles, more preferably 2.3 particles, more preferably 2.2 particles, more preferably 2.1 particles, more preferably 2.0 particles, more preferably 1.9 particles, more preferably 1.8 particles, more preferably 1.7 particles, even more preferably 1.6 particles, and most preferably 1.5 particles. Another preferred threshold is that the number of particles with a diameter of at least 2 μm is, in each case, 8.7 particles per square centimeter of the total surface area of ​​the outer surface of the container wall of at least a portion of the containers in the plurality of containers, preferably 8.5 particles, more preferably 8.3 particles, more preferably 8.1 particles, more preferably 7.9 particles, more preferably 7.7 particles, more preferably 7.5 particles, more preferably 7.3 particles, more preferably 7.1 particles, more preferably 6.9 particles, more preferably 6.7 particles, more preferably 6.5 particles, more preferably 6.3 particles, more preferably 6.1 particles, more preferably 5.9 particles, more preferably 5.7 particles, more preferably 5.5 particles, more preferably 5.3 particles, more preferably 5.1 particles, more preferably 4.9 particles, even more preferably 4.7 particles, and most preferably 4.5 particles.

[0094] In Embodiment 2 of Method 3 according to the invention, this method is designed according to Embodiment 1 thereof, wherein the transport simulation includes one or more of Arrangements A to J as specified in ASTM D4169-16. Alternatively or preferably, the transport simulation includes a rotating plane drop test or a random vibration test, or both. A preferred rotating plane drop test is described in the Test Methods section below. A preferred random vibration test is described in the Test Methods section below.

[0095] In embodiment 3 of the method 3 according to the present invention, this method is designed according to embodiment 1 or 2, wherein in method step D], at least one filled container is obtained, wherein the method further includes the following method steps

[0096] D. The auxiliary part is preferably connected to at least one filled container via a tapered fitting or via threads or both.

[0097] The preferred auxiliary component is selected from one of the group consisting of a needle, a nozzle, and a tube, or a combination of at least two of them. The preferred needle is a hypodermal injection needle.

[0098] The contribution to solving at least one of the objectives of the invention is made by embodiment 1 of the use of the component of the invention in any embodiment of the invention, said component being used for storing or transporting at least a portion of a plurality of containers.

[0099] A contribution to solving at least one of the objectives of the invention is made by embodiment 1 of use 2 of the filling machine, which is used to fill at least a portion of the containers of a plurality of containers of the component of the invention according to any embodiment of the invention with a pharmaceutical composition or a cosmetic composition or both. Preferably, at least a portion of the containers of the plurality of containers are held by a holding device as described in the context of the component.

[0100] Features described as preferred in one category of the invention (e.g., according to the components) are similarly preferred in embodiments of other categories of the invention.

[0101] container

[0102] The containers among the plurality of containers according to the invention can have any size or shape that a person skilled in the art would consider appropriate for the context of the invention. Preferably, a first end of the container includes a drain hole that allows the discharge of a pharmaceutical composition from the internal volume of the container. In that case, the container wall only partially surrounds the internal volume of the container. The container is preferably a glass container whose glass wall (container wall) at least partially surrounds the internal volume of the container. Preferably, the glass wall is a one-piece design. The glass wall can preferably be made by blowing glass melt, or by preparing a glass tube (preferably in the form of a hollow cylinder), forming the bottom of the container from one end of the tube, thereby closing the tube at that end, and forming the top region of the container from the opposite end of the tube. Preferably, the glass wall is transparent. Alternatively, the container wall is preferably made of a polymer. In that case, the container wall is also preferably transparent.

[0103] As used herein, internal volume refers to the total volume inside a container. This volume is determined by filling the container with water to the rim and measuring the volume of water that can be held up to the rim. Therefore, the internal volume used herein is not the nominal volume commonly referred to in the pharmaceutical field. The nominal volume may, for example, be about 0.5 times smaller than the internal volume.

[0104] Glass

[0105] The container wall of each of the plurality of primary packaging containers preferably comprises glass, more preferably substantially composed of such glass. This glass can be any type of glass and can have any composition that a person skilled in the art would consider suitable for the context of this invention. Preferably, the glass is suitable for pharmaceutical packaging. Particularly preferably, the glass belongs to Type I glass according to the definition of glass type in Section 3.2.1 of the 7th edition of the European Pharmacopoeia 2011. Additionally or alternatively, preferably, the glass is selected from the group consisting of borosilicate glass, aluminosilicate glass, and fused silica; or a combination of at least two thereof, with aluminosilicate glass being particularly preferred. In each case, based on the total weight of the glass, the Al₂O₃ content in the aluminosilicate glass, as used herein, is greater than 8% by weight, preferably greater than 9% by weight, and particularly preferably 9 to 20% by weight. In each case, based on the total weight of the glass, the preferred aluminosilicate glass has a B₂O₃ content of less than 8% by weight, preferably less than 7% by weight, and particularly preferably 0 to 7% by weight. In each case, based on the total weight of the glass, the B2O3 content of the borosilicate glass used herein is at least 1 wt%, preferably at least 2 wt%, more preferably at least 3 wt%, more preferably at least 4 wt%, even more preferably at least 5 wt%, and particularly preferably 5 to 15 wt%. In each case, based on the total weight of the glass, the preferred borosilicate glass has an Al2O3 content of less than 7.5 wt%, preferably less than 6.5 wt%, and particularly preferably 0 to 5.5 wt%. On the other hand, in each case, based on the total weight of the glass, the Al2O3 content of the borosilicate glass is 3 to 7.5 wt%, preferably 4 to 6 wt%.

[0106] A further preferred embodiment of the invention is that the glass is substantially free of boron (B). Here, "substantially free of B" means that the glass does not contain B that has been intentionally added to the glass composition. This means that B may still be present as an impurity, but preferably in each case at a proportion not exceeding 0.1% by weight, more preferably not exceeding 0.05% by weight based on the weight of the glass.

[0107] Holding device

[0108] The retaining device of the component according to the invention can generally be any device that a person skilled in the art would consider to hold multiple containers by means of multiple retaining elements. Preferred retaining devices have been prepared by deep drawing or injection molding. Alternatively or preferably, the retaining device is made of one or more plastics.

[0109] matrix

[0110] The substrate of the retaining device can be any shape or material that a person skilled in the art would consider appropriate for the context of this invention. Preferably, the substrate is made of one or more plastics. Alternatively or additionally, preferably, the substrate has a Shore A hardness of at least 80, more preferably at least 90. Alternatively or additionally, preferably, the substrate has a plate-like shape. Preferably, the width and length of the substrate are each at least 3 times, more preferably at least 5 times, even more preferably at least 10 times, and most preferably at least 20 times the thickness of the substrate. Preferably, the plurality of holes consists of 4 to 500 holes, preferably 9 to 400 holes, more preferably 12 to 300 holes, more preferably 16 to 200 holes, more preferably 16 to 160 holes, more preferably 16 to 100 holes, more preferably 16 to 90 holes, more preferably 16 to 80 holes, more preferably 16 to 70 holes, even more preferably 16 to 60 holes, and most preferably 16 to 50 holes. Alternatively or concurrently, preferably, the holding device of the present invention is preferably configured to hold 4 to 500, preferably 9 to 400, more preferably 12 to 300, more preferably 16 to 200, more preferably 16 to 160, more preferably 16 to 100, more preferably 16 to 90, more preferably 16 to 80, more preferably 16 to 70, even more preferably 16 to 60, and most preferably 16 to 50 containers. Furthermore, the holes in the plurality of holes in the first surface can be any kind of hole that a person skilled in the art would consider suitable for accommodating containers, so that the containers can be held by the holding element. Preferred holes are recesses or through holes, with through holes being particularly preferred. Preferred through holes have a circular cross-section. Particularly preferred through holes are cylindrical. This means that the side surfaces of the through holes are cylindrical shell surfaces. Alternatively or concurrently, preferably, the holes are arranged in a regular pattern on the first surface, preferably arranged in an array of rows and columns preferably perpendicular to each other.

[0111] Retaining element

[0112] The retaining element of the retaining device can generally be any design that a person skilled in the art would consider for holding multiple containers to the retaining device. Preferably, the retaining element is manufactured integrally with the base, and more preferably with the retaining device. Alternatively, preferably, the retaining element is designed and arranged to hold multiple containers by form-fitting or friction locking, or both, with form-fitting being particularly preferred. Preferably, if the retaining device is vertically positioned, the form-fitting holds the containers against gravity. Alternatively, preferably, the retaining element is designed and arranged to substantially prevent any movement of the containers relative to the retaining device during vibration testing. Alternatively, preferably, the retaining element is designed and arranged to employ a retaining configuration and hold the containers within this retaining configuration, and is converted to a release configuration intended for removing the containers from the retaining device, and vice versa. Preferably, converting the retaining element from a retaining configuration to a release configuration (and vice versa) involves at least partial movement of the retaining element relative to the base. Preferably, in both the retaining and release configurations, the retaining element is attached to the base.

[0113] Pharmaceutical and cosmetic compositions

[0114] In the context of this invention, every pharmaceutical composition and every cosmetic composition that a person skilled in the art considers suitable is taken into account. A pharmaceutical composition is a composition comprising at least one pharmaceutical active ingredient. A preferred pharmaceutical active ingredient is a vaccine. A cosmetic composition is a composition comprising at least one cosmetic active ingredient. A preferred cosmetic active ingredient is hyaluronic acid or botulinum toxin. Pharmaceutical or cosmetic compositions can be fluid or solid or both, with fluid compositions being particularly preferred herein. Preferred solid compositions are granular, such as powders, bulk tablets, or bulk capsules. Further preferred pharmaceutical or cosmetic compositions are parenteral medications, i.e., compositions intended for administration via a parenteral route, which can be any non-enteric route. Parenteral administration can be performed by injection, for example using a needle (typically a hypodermic needle) and a syringe, or by inserting an indwelling catheter.

[0115] Test methods

[0116] The following test methods will be used in the context of this invention. Unless otherwise stated, measurements must be performed at an ambient temperature of 23°C, an ambient pressure of 100 kPa (0.986 atmospheres), and a relative humidity of 50%.

[0117] Transportation Simulation

[0118] The transportation simulation was conducted according to ASTM D4169–16. Specifically, the transportation simulation consisted of two sequences, performed sequentially using the same sample. The laboratory environmental conditions were:

[0119] -Temperature: 15 to 35℃

[0120] - Relative humidity: <85%

[0121] -Atmospheric pressure: 860 to 1060 hPa

[0122] sample

[0123] The sample is a pallet unit, consisting of a wooden pallet on which boxes made of corrugated cardboard are stacked, resulting in the following overall dimensions:

[0124] - Length: 1200mm

[0125] Width: 800mm

[0126] - Height: 940mm.

[0127] These boxes are held together by stretch plastic foil. Each box contains a component of the same type as the component being tested. These boxes do not contain any additional filler material. Therefore, each component consists of a holding device filled with the same empty container.

[0128] first sequence

[0129] The first sequence was performed according to Schedule A – Mechanical Handling – Group Loading as described in Section 10.3.2 of ASTM D4169–16. A rotating flat drop test was performed according to Method C of ASTM D6179. The drop height was selected from the table in Section 10.3.2.3 of ASTM D4169–16 based on Assurance Level II. The test consisted of one drop from each of the opposite bottom edges of the specimen. One edge of the specimen was supported by the floor. The other side was raised to the drop height and then released to land flat on the impact surface (bottom of the wooden pallet). This process was performed for each opposite bottom edge, for a total of four drops. The following test procedures were performed:

[0130] 1. Support edge 3-6, raised edge 3-5; drop to surface 3

[0131] 2. Support edge 3-5, raised edge 3-6, drop to surface 3;

[0132] 3. Support edge 2-3, raise edge 3-2; drop onto surface 3

[0133] 4. Support edge 3-4, raised edge 3-4; drop onto surface 3

[0134] If any sample box has moved on the tray during any of steps 1 through 3, it should be pushed back into place before proceeding to the next step. At the end of step 4, all boxes should be pushed back to their original positions on the tray.

[0135] second sequence

[0136] The second sequence was performed according to the schedule D-stack-vibration described in Section 12.2 of ASTM D4169–16. Random vibration testing was conducted according to ASTM D4728. During the test, the samples were in normal shipping orientation, i.e., the wooden pallet was at the bottom. The samples were loaded according to Section 11.4 of ASTM D4169–16. The maximum load TL was calculated according to Formula (3) given in Section 11.4 of ASTM D4169–16. Where H = 2.7 m and F = 1. Other parameters for the second sequence are:

[0137] Transportation loop curve:

[0138] -0.40G rms 40min

[0139] -0.54G rms 15min

[0140] -0.70G rms 5min

[0141] - Number of loops: 1

[0142] -Total duration: 1 hour on surface 3.

[0143] Air curve:

[0144] -AL II / G rms 1.05

[0145] - Test duration: 2 hours on surface 3.

[0146] Particle load after transport simulation

[0147] Following the transport simulation described above, the particle load on the outer surface of the container of the component under study is then determined within a specific size range (particle category) of particles per square centimeter of the total outer surface area. Between the transport simulation and particle load determination, any further processing of the sample that might lead to the formation of more particles should be avoided.

[0148] Liquid Particle Counting System

[0149] The particle load in the container of the component under study was determined using a liquid particle counting system, which included a Pacific Scientific Hiac Royco particle counter, model 9703 (F4-088), and a desktop computer running PharmSpec 3.4.0 software with the particle counter. Typically, the particle counter draws the test liquid through a riser tube and guides it through a light scattering sensor. The signal from the light scattering sensor is read out and processed by the software. In this testing method, only the H2O-EDI-2-T from Sartorius AG, Göttingen, Germany, was used. The Advance EDI (10 L / h) desktop system produces particle-free water for cleaning, rinsing, and washing, as well as as a zero sample for any filter exchange and for preparing test liquids. This system is designed for preparing Type II pure water. It has a flow rate of 10 liters per hour.

[0150] Preparation of Particle Counter

[0151] Fill the container with the necessary flushing medium (particle-free water) and the test medium (test solution) at least one hour before testing. Run the particle counter under laminar flow conditions. Before starting the test, clean the entire laminar flow workstation running the workflow with a damp, particle-free cloth. The lifting arm connected to the pipette can be controlled via the control panel. Before the first measurement, the sampler must be cleaned and adjusted so that the pipette is immersed as deeply as possible in the test liquid without touching the bottom of the container. Adjust the container; subsequent measurements will also be performed using this container. Set the lifting arm to its lowest position, then move it back to the starting position. To clean the sampler, fill the container, which has been flushed three times with particle-free water, with at least 35 ml of particle-free water and place it under the lifting arm. Move the lifting arm to the previously set lower position. Again, the lifting arm must not touch the bottom of the container. Start the automatic flushing program. Each cleaning run consumes 10 ml of liquid. Perform four cleaning runs. Under no circumstances should air be drawn in. Therefore, the container must contain at least 35 ml of particle-free water. After cleaning, move the lifting arm to the upper position.

[0152] Zero samples

[0153] Before starting the test, the particle content of the particle-free water used to prepare the test solution must be checked. To do this, the container used for measurement should be rinsed three times with particle-free water. Then, fill the container with 40 ml of particle-free water as a zero sample. After allowing the zero sample to stand for at least 2 minutes to degas, the test can begin. A particle counter measures the number of particles in a given volume of particle-free water. All possible particle sizes must be recorded. To do this, the machine aspirates and tests 5 ml of liquid six times. The first measurement is invalid. The acceptance criterion is set at a maximum of 25 particles with a diameter of at least 10 μm per 25 ml of particle-free water. If this value is not met, the preparation of the particle-free water must be adjusted, and the zero sample measurement must be repeated until the acceptance criterion is met.

[0154] Test liquid

[0155] Remove the stretch foil from the cardboard box. Remove the box containing the component to be studied from the tray and open it under laminar flow. All further steps are performed under laminar flow. Remove the component to be studied from the box. Prepare a glass beaker containing sufficient particle-free water to immerse a primary packaging container, placed vertically, to half its length. In any case, use at least 40 ml of particle-free water, hereinafter referred to as pool water. Rinse the glass beaker with particle-free water at least 3 times beforehand. Seal all openings of the primary packaging container of the component to be studied with a stopper, which has been rinsed with particle-free water at least 3 times beforehand. Place each primary packaging container vertically, immersing half its length in the pool water (the aforementioned particle-free water), and manually stir to create a stirring motion while maintaining the vertical orientation for 5 seconds. In the case of syringes, vertical orientation means the syringe tip is facing upwards. The test liquid is the pool water in which all primary packaging containers of the component have been rinsed as described above.

[0156] Measurement

[0157] The test liquid should be filled into the container at least one hour before testing. A particle counter measures the number of particles larger than 2 μm, 5 μm, 10 μm, 15 μm, 25 μm, 50 μm, 75 μm, and 100 μm. For this purpose, the machine performs six tests on 5 ml of test liquid, with the first measurement being discarded. Therefore, the minimum volume of test liquid is 35 ml. For each of the above particle size grades, the number of particles per square centimeter is determined by dividing the number of particles in the test liquid as determined by the particle counter by the sum of the outer surface areas of the primary packaging containers in that component.

[0158] Wall thickness and wall thickness tolerance

[0159] The wall thickness and its deviation from the average wall thickness (tolerance) are determined according to the following standards for the corresponding type of container:

[0160] DIN ISO 8362-1 for use in vials,

[0161] DIN ISO 9187-1 for ampoules,

[0162] DIN ISO 110 4 0-4 for syringes,

[0163] DIN ISO 13926-1 for cylindrical cartridges, and

[0164] DIN ISO 11040-1 for dental medicine cartridges.

[0165] Troubleshooting (discharge failure)

[0166] NPO resistance

[0167] In this document, "NPO" stands for needle ejection and indicates that the needle assembly (specifically, the needle assembly connected to the syringe body via a Luer lock connection) suddenly detaches from the syringe body. NPO resistance represents a threshold force, in the context of this test procedure, applied to the plunger rod introduced into and operatively connected to the syringe body. NPO resistance is defined as the highest threshold force below which needle ejection occurs in no more than 1.8% of the test syringe bodies. At least 56 measurements are required on syringe bodies of the same construction and design to provide meaningful results for NPO resistance. Under high pressure (triggered by a force applied to the syringe body via the plunger rod), the needle assembly may begin to rotate at high speed and detach from the syringe body; that is, the inner cone (Luer connector) of the needle assembly, which is complementary to the outer cone of the syringe body, may loosen, and thus, the needle assembly may separate from the syringe body.

[0168] Leakage resistance

[0169] In this paper, leakage refers to leakage occurring between the syringe body and the needle assembly due to applied forces and pressures. Leakage resistance represents a threshold force, in the context of this test procedure, applied to a plunger rod introduced into and operatively connected to the syringe body. Leakage resistance is defined as the highest threshold force below which no more than 1.8% of the tested syringe bodies leak. At least 56 measurements are required on syringe bodies with the same construction and design to provide meaningful leakage resistance results.

[0170] Measurement

[0171] In the test procedure used to measure NPO resistance and leakage resistance, the syringe body to be tested is arranged vertically in the testing machine and held in the proximal region of the syringe body. The testing machine used is a general-purpose testing machine "Test 106.2kN" from TestT. The syringe body to be tested is connected to the needle assembly via a Luer lock connector. To create a Luer lock connection through the Luer lock connector mating parts, the needle assembly is screwed to the distal portion of the syringe body with a torque of 12 Ncm. The test procedure is designed specifically for use with the Terumo 27G x 1 / 2 needle assembly (standard wall needle, see NN-2713R). The needle assembly for the test procedure includes an inner cone that serves as a mating part for the Luer lock connector and two fins arranged on the outer circumference of the needle interface of the needle assembly. The needle assembly for the test procedure includes a cannula or hollow needle with a thickness of 27G and a length of 0.5 inches, approximately 13 mm (27G x 1 / 2). Before testing, the cannula is flattened and thus sealed with a hammer for testing purposes. For the test procedure, a dry Luer lock connection is created by screwing the needle assembly onto the syringe body, and then using a syringe (available from Fresenius Kabi Deutschland GmbH, Germany) MCT 20% volume fully filled syringe. The test procedure is performed using unsterilized components (syringe body, needle assembly, plunger rod). After the syringe is filled, the plunger rod is introduced into and operatively connected to the syringe body, but the syringe body and plunger rod are still in the initial, i.e., unactuated position at the start of the test procedure. For the current test procedure, a standard plunger rod provided for the corresponding syringe body to be tested will be used.

[0172] A force is applied perpendicularly to the proximal end of the plunger rod through the test plunger of the testing machine. The test plunger moves in the direction of the distal portion of the syringe body at a constant test speed of 12.6 mm / min. The force acting on the plunger rod continuously increases to a maximum of 420 N. During the test, the test plunger moves a distance of 15 mm. The applied force is detected by a force sensor at a scan rate of 200 Hz. The test plunger moves forward, or the applied force is increased until leakage and / or NPO occurs, or until the maximum force of 420 N is reached. If the measured force suddenly drops by at least 30%, the test is stopped, i.e., leakage and / or NPO is identified. The applied force at which leakage and / or NPO occurs is recorded and linked to information about whether leakage and / or NPO has occurred under this force. Based on the recorded measurements, the previously described NPO resistance and leakage resistance are then determined. Leakage and NPO are also referred to herein as troubleshooting.

[0173] The invention is described in more detail below with reference to embodiments and accompanying drawings, wherein the embodiments and drawings are not intended to limit the invention in any way. Furthermore, unless otherwise stated, the drawings are not drawn to scale.

[0174] For each embodiment and comparative example, 36 types from Schott AG were selected. Commercially available polymer syringe loading and holding devices (also known as nesting pieces) are available in ml / lg sizes. These syringes are composed of cyclic olefin copolymers (COC). Each nesting piece contains 6 rows and 6 columns of holes perpendicular to them in the matrix to accommodate 36 syringes. The specific types of nesting pieces are given in Table 1 below, with reference to the accompanying drawings showing a detailed view of how the syringes are held in the nesting pieces. Figure 2 and 8 As shown, each loaded nested component of the embodiments and comparative examples is placed into the basin-shaped component. The filled basin-shaped component is sealed by sealing the vent cap to the upper edge of the basin-shaped component via hot melt adhesive.

[0175] Table 1

[0176] Holding device in the attached drawing Example 1 4a) and 4b) Example 2 5a) and 5b) Example 3 6a) and 6b) Comparative Example 1 14 Comparative Example 2 17

[0177] The transport simulation described in the above-described test method section was performed on 10 enclosed basin-shaped components for each embodiment and comparative example. Subsequently, as described in the test method section above, the particle load on the outer surface of 36 syringes was determined. For each of Embodiments 1 to 3, the number of particles with a diameter of at least 5 μm did not exceed 2.7 per square centimeter, and the number of particles with a diameter of at least 2 μm did not exceed 8.7 per square centimeter. In Comparative Examples 1 and 2, the number of particles with a diameter of at least 5 μm was greater than 2.7 per square centimeter, and the number of particles with a diameter of at least 2 μm was greater than 8.7 per square centimeter. In particular, Embodiment 3 showed a number of particles with a diameter of at least 5 μm of 2.47 per square centimeter and a number of particles with a diameter of at least 2 μm of 6.47 per square centimeter. Comparative Example 1 showed a number of particles with a diameter of at least 5 μm of 2.77 per square centimeter and a number of particles with a diameter of at least 2 μm of 8.81 per square centimeter. Table 2 below summarizes the results for all embodiments and comparative examples. In this context, ++ indicates fewer particles than +, and + indicates fewer particles than -.

[0178] Table 2

[0179]

[0180] Following the transport simulation described in the test methods section above, 100 syringes from each embodiment and comparative example were further processed in an automated manner in a standard filling machine. The basin was opened by cutting open the cap with a knife, and the syringes were removed from the nest by a robotic arm. The robotic arm gripped the syringes with a clamp and moved them to the filling station via a rotational motion. The number of processing failures was calculated for each embodiment and comparative example, particularly failures to properly grasp and withdraw the syringes from the nest and failure to firmly grasp the syringes during the rotational motion.

[0181] The transport simulation described in the above-described test method section was performed on the additional 10 basin-shaped pieces in each embodiment and comparative example. Subsequently, as described above in the test method section, the NPO resistance and leakage resistance of 100 syringes randomly selected from those 10 basin-shaped pieces in each embodiment and comparative example were determined.

[0182] Furthermore, after conducting the transportation simulation described in the aforementioned test methods section, the 10 basin-shaped syringes in each embodiment and comparative example were further processed by vacuum-packing them in plastic foil bags. The packaged containers were placed in a cardboard box, the box was sealed, and then manually shaken for 5 minutes. Subsequently, the box was opened, and the foil bags were examined with the naked eye and an optical microscope (10x magnification) for damage such as scratches, pinholes, and tears.

[0183] The results of the above study are summarized in Table 3 below. ++ indicates a more favorable outcome than +, and + is still more favorable than -.

[0184] Table 3

[0185] Troubleshooting NPO resistance Leakage resistance Low rate of damaged foil bags Example 1 + + + + Example 2 + + + + Example 3 ++ ++ ++ ++ Comparative Example 1 - - - - Comparative Example 2 - - - - Attached Figure Description

[0186] Unless otherwise stated in the instruction manual or specific drawings:

[0187] Figure 1 A schematic diagram of the components according to the present invention is shown in cross-section;

[0188] Figure 2 A schematic diagram of another component according to the invention is shown;

[0189] Figure 3 A schematic diagram of a container for a component according to the present invention is shown;

[0190] Figure 4a) and 4b) A cross-sectional view is shown. Figure 1 A detailed schematic diagram of the components;

[0191] Figure 5a) and5b) A schematic diagram showing details of another component according to the invention is presented in cross-sectional view;

[0192] Figure 6a) and 6b) A schematic diagram showing details of another component according to the invention is presented in cross-sectional view;

[0193] Figure 7 A schematic diagram of another component according to the invention is shown in cross-section;

[0194] Figure 8 A schematic diagram of another component of the container according to the invention, having a holding device and being removed from the packaging container, is shown;

[0195] Figure 9 A schematic diagram of a container for a component according to the present invention is shown;

[0196] Figure 10a) and 10b) A cross-sectional view is shown. Figure 7 A detailed schematic diagram of the components;

[0197] Figure 11 A flowchart of a method for preparing the components of the present invention is shown;

[0198] Figure 12 A flowchart of a method according to the present invention is shown, which includes filling a container with a pharmaceutical composition;

[0199] Figure 13 A flowchart of a method according to the present invention is shown, which includes shaking the components of the present invention and determining the particle load;

[0200] Figure 14 A schematic diagram showing details of a nested component that does not conform to the present invention is provided.

[0201] Figure 15 A schematic diagram showing details of another nested component that does not conform to the present invention is provided;

[0202] Figure 16 A schematic diagram showing details of another nested component that does not conform to the present invention is provided; and

[0203] Figure 17 A schematic diagram showing details of another nested component that does not conform to the present invention is provided. Detailed Implementation

[0204] Figure 1A schematic cross-sectional view of a component 100 according to the invention is shown. This component 100 includes a retaining device 101 comprising a base 104 and a plurality of retaining elements 102 disposed on the base 104. Furthermore, the component 100 includes a plurality (36) of containers 103. These containers 103 are... Figure 3 A syringe of the type shown, but without a plunger 311. The base 104 includes a plurality of holes 107 located in a first surface 105 of the base 104. Each container 103 extends through the first surface 105 into one of the holes 107. Each hole 107 is the inlet of a cup formed by the base 104. A retaining element 102 is arranged in the cup. Opposite to the first surface 105, the base 104 has another surface 106. The first surface 105 and the other surface 106 are planar parallel to each other. Furthermore, both the first surface 105 and the other surface 106 extend in the width and length directions of the base 104. The length of the base 104 extends in a direction from left to right in the figure. In this direction, the holes 107 are arranged in a row. The width of the base 104 extends into the plane of the figure in a direction perpendicular to the first direction. In the latter direction, the holes 107 are arranged in a column. The substrate 104 has a total of 36 holes 107 for accommodating 36 containers 103. Each container 103 includes a container wall 307 that partially surrounds the container interior 308 (see...). Figure 3 The outer surface of the container wall 307 faces away from the container interior 308. Furthermore, each container 103 is detachably held by two retaining elements 102 that conform to the shape of the outer surface of the corresponding container wall 307. The retaining elements 102 are designed as plastic springs. For details regarding the retaining elements 102, see [link to relevant documentation]. Figure 4a) and 4b) After performing the transport simulation described in the Test Method section on component 100, the number of particles with a diameter of at least 5 μm does not exceed 2.7 particles per square centimeter of the total surface area of ​​the outer surfaces of all containers 103 in the plurality of containers 103, and the number of particles with a diameter of at least 2 μm does not exceed 8.7 particles per square centimeter of the total surface area of ​​the outer surfaces of all containers 103 in the plurality of containers 103.

[0205] Figure 2 A schematic diagram of another component 100 according to the present invention is shown. This component 100 includes having Figure 1 The holding device 101 and the container 103 are components 100. Furthermore, Figure 2Component 100 includes a packaging container 201 designed as a basin. The packaging container 201 consists of a packaging container wall 202 partially surrounding a packaging container interior 203 and a lid 204 sealed to the upper edge of the packaging container wall 202. The packaging container wall 202 is made of PET, while the lid 204 is made of a breathable multilayer sheet. The packaging container 201 can be closed by completely sealing the lid 204 to its upper edge. A retaining device 101 and the container 103 are arranged within the packaging container interior 203. The packaging container 201 includes a flat packaging container bottom 205 formed by the packaging container wall 202. The inner surface of the packaging container wall 202 faces the packaging container interior 203. Figure 2 After the component 100 is subjected to the transport simulation described in the test method section, the number of particles with a diameter of at least 5 μm does not exceed 2.7 per square centimeter of the total surface area of ​​the outer surfaces of all containers 103 in the plurality of containers 103, and the number of particles with a diameter of at least 2 μm does not exceed 8.7 per square centimeter of the total surface area of ​​the outer surfaces of all containers 103 in the plurality of containers 103.

[0206] Figure 3 A schematic diagram of a container 103 of a component 100 according to the present invention is shown. The container 103 includes a container wall 307 partially surrounding a container interior 308. The container wall 307 is formed from top to bottom in the following order: a first end 301, which includes a discharge port 304; a body portion 302; and a second end 303. The body portion 302, also referred to in the art as a cylinder, is a hollow cylinder. The second end 303 includes another port 310. The port area of ​​the discharge port 304 is smaller than the port area of ​​the second port 310. The second port 310 receives a plunger 311. The second end 303 also includes an edge, also referred to in the art as a flange, which laterally projects beyond the body portion 302 and surrounds the second port 310. The container wall 307 is made of a cyclic olefin copolymer. The first end 301 includes a connecting element, which is a protrusion 305 of a Luer connector. The connecting element includes threads for connecting a hypodermic needle to the container 103. The threads are arranged in a sleeve. Figure 1 The container 103 of component 100 is Figure 3 A syringe of the type shown, but without plunger 311. Furthermore, Figures 4a) to 6b) It also shows Figure 3 The container 103 is of the same type, without plunger 311.

[0207] Figure 4a )and Figure 4b (shown in cross-sectional view) Figure 1 A detailed schematic diagram of component 100. Figure 4a )and Figure 4bEach figure in the diagram shows a container 103 housed in the same hole 107 in the first surface 105 of the base 104 of the holding device 101. The hole 107 is the inlet of the cup. Figure 4a In this configuration, container 103 is detachably held by two retaining elements 401 that engage with the outer surface of the container wall 307. The retaining elements 401 are designed as plastic springs. Figure 4a In this configuration, the retaining elements 401 are in their retaining configuration. Here, the edge of the other end 303 of the container 103 is fixed between the retaining element 401 and the bottom of the cup. By pulling the container 103 upward with a force exceeding a threshold force, the springs can elastically deform and rotate about their connection point with the cup. In this way, the retaining elements 401 can change from their retaining configuration to their release configuration. Figure 4b The image shows the retaining element 402 in its release configuration. Here, the form fit is released, and the container 103 can be withdrawn from the retaining device 101. By pushing the container 103 downward into a cup having an edge extending beyond the retaining element 402, the retaining elements 402 can be reverted to their retaining configuration, and thus, the form fit can be restored.

[0208] Figure 5a )and Figure 5b A schematic diagram showing details of another component 100 according to the invention is presented in cross-sectional view. Besides maintaining the design of element 102, component 100 is similar to... Figure 1 Component 100 is the same. Therefore, Figure 5a )and Figure 5b ) shows Figure 4a )and Figure 4b Alternatives to ). Figure 5a )and Figure 5b Each figure in the diagram shows a container 103 housed in the same hole 107 in the first surface 105 of the base 104 of the holding device 101. The hole 107 is the inlet of the cup. Figure 5a In this configuration, container 103 is detachably held by two retaining elements 401. The retaining elements 102 are designed as plastic springs. Figure 5a In this configuration, the retaining elements 401 are in their retaining configuration. Here, the retaining elements 401 are in close contact with the outer surface of the container wall 307, thereby holding the container 103 in place. By pulling the container 103 upward with a force exceeding a threshold force, the springs can elastically deform and rotate about their connection point with the cup. In this way, the retaining elements 401 can change from their retaining configuration to their releasing configuration. Figure 5bThe image shows the retaining element 402 in its release configuration. Here, the container 103 can be withdrawn from the retaining device 101. By pushing the container 103 downward into a cup having an edge extending beyond the retaining element 402, the retaining elements 402 can revert to their retaining configuration to hold the container 103 in place again.

[0209] Figure 6a )and Figure 6b A schematic diagram showing details of another component 100 according to the invention is presented in cross-sectional view. Besides maintaining the design of element 102, component 100 is similar to... Figure 1 The components are the same as 100. Figure 6a )and Figure 6b The holding device 101 of component 100 is combined with Figure 4a )and Figure 4b The holding element 102 and Figure 5a )and Figure 5b () holding element.

[0210] Figure 7 A schematic cross-sectional view of another component 100 according to the invention is shown. This component 100 includes a retaining device 101 comprising a base 104 and a plurality of retaining elements 102 disposed on the base 104. Furthermore, the component 100 includes a plurality (36) of containers 103. These containers 103 are... Figure 9 The illustrated vial is shown. The substrate 104 includes a plurality of holes 107 in a first surface 105 of the substrate 104. Each container 103 extends through the first surface 105 into one of the holes 107. Each hole 107 is the inlet of a cup formed by the substrate 104. A retaining element 102 is arranged in the cup. Opposite to the first surface 105, the substrate has another surface 106. The first surface 105 and the other surface 106 are planar parallel to each other. Furthermore, both the first surface 105 and the other surface 106 extend in the width and length directions of the substrate 104. The length of the substrate 104 extends in a direction from left to right in the figure. In this direction, the holes 107 are arranged in a row. The width of the substrate 104 extends into the plane of the figure in a direction perpendicular to the first direction. In the latter direction, the holes 107 are arranged in a column. The substrate 104 has a total of 36 holes 107 accommodating 36 containers 103. Each container 103 includes a container wall 307 that partially surrounds the container interior 308 (see...). Figure 9 The outer surface of the container wall 307 faces away from the container interior 308. Furthermore, each container 103 is detachably held by two retaining elements 102 that conform to the shape of the outer surface of the corresponding container wall 307. The retaining elements 102 are designed as plastic springs. For details regarding the retaining elements 102, see [link to relevant documentation]. Figure 10a )and Figure 10b ).

[0211] Figure 8 A schematic diagram of another component 100 according to the present invention is shown. This component 100 is related to... Figure 7 The components are the same, but it has 5 rows and 5 columns of holes 107, therefore only 25 containers 103. Furthermore, Figure 8 Component 100 includes a packaging container 201 designed as a basin. The packaging container 201 includes a packaging container wall 202 that partially surrounds the packaging container interior 203. The packaging container wall 202 is made of PET. The basin can be closed by sealing a lid 204 (not shown) to the upper edge of the packaging container wall 202. Here, the retaining device 101 and the container 103 are shown outside the packaging container 201. This is for illustrative purposes only. According to the invention, the retaining device 101 and the container 103 are arranged within the packaging container interior 203. The packaging container wall 202 includes stepped protrusions 801 designed to retain the retaining device 101 such that the container 103 is positioned above the flat packaging container bottom 205 formed by the packaging container wall 202. The inner surface of the packaging container wall 202 faces the packaging container interior 203.

[0212] Figure 9 A schematic diagram of a container 103 according to a component 100 of the present invention is shown. The container 103 includes a container wall 307 that partially surrounds a container interior 308. The container wall 307 is formed from top to bottom in the following order: a first end portion 301; a body portion 302; and a second end portion 303. The first end portion 301 includes a discharge port 304, a flange 901, and a neck 902. The flange 901 and the neck 902 each have the shape of a hollow cylinder. The body portion 302 follows the first end portion 301 via a shoulder portion 903. The body portion 302 is a hollow cylinder. The second end portion 303 follows the body portion 302 via a heel portion 904. In addition to the heel portion 904, the second end portion 303 also includes an upright base 905. The container wall 307 is made of type I glass. Figure 7 and Figure 8 The container 103 of component 100 is Figure 9 The type of vial shown. Furthermore... Figures 10a) to 10b) It also shows Figure 9 The type of container 103.

[0213] Figure 10a Figures a and b) are shown in cross-sectional view. Figure 7 A detailed schematic diagram of component 100. Figure 10a )and Figure 10b Each figure in the series shows a container 103 housed in the same hole 107 in the first surface 105 of the base 104 of the holding device 101. Figure 10aIn this configuration, container 103 is detachably held by two retaining elements 401 that engage with the outer surface of the container wall 307. The retaining elements 401 are designed as plastic springs. Figure 10a In this context, the retaining elements 401 are in their retaining configuration. Here, the shoulder 903 of the container 103 (see...) Figure 9 The retaining element 401 is fixed between itself and the bottom of the cup. By pulling the container 103 upward with a force exceeding a threshold force, the springs can elastically deform and rotate about their connection point with the cup. In this way, the retaining element 401 can be changed from its retaining configuration to its releasing configuration. Figure 10b The image shows the retaining element 402 in its release configuration. Here, the form fit is released, and the container 103 can be pulled out from the retaining device 101. By pushing the container 103 down to the bottom of the cup, the retaining elements 402 can be turned back into their retaining configuration, and thus, the form fit can be restored.

[0214] Figure 11 The invention illustrates a method for preparing... Figure 2 The flowchart of method 1100 for component 100. In method step A) 1101, the following is provided: Figure 2 The context describes a holding device 101, multiple containers 103, a packaging container 201, and a lid 204. Subsequently, in method step B) 1102, 36 containers 103 are loaded into the holding device 101 by inserting each container 103 into a cup via holes 107. This transforms the holding elements 102 from a release configuration to a holding configuration, such that each container 103 is removably held by contact between two holding elements 102 and the outer surface of the container wall 307 of the corresponding container 103. In method step C) 1103, the holding device 101 with the containers 103 is placed into the packaging container 201. In the subsequent method step D) 1104, the packaging container 201 is closed by heat-sealing the lid 204 to the edge of the packaging container wall 202 via hot melt adhesive. Figure 2 Component 100 can be further processed in method steps E) 1105 and F) 1106 by placing the packaging container 201 having the holding device 101 and the container 103 into the outer packaging and closing the outer packaging. Here, the outer packaging can be a plastic bag, which is heat-sealed to close.

[0215] Figure 12 A flowchart of a method 1200 according to the present invention is shown. This method 1200 includes providing Figure 7 Method step A.1201 of component 100. Furthermore, in method step B.1202, the pharmaceutical composition is filled into each of the 36 containers 103.

[0216] Figure 13A flowchart of another method 1300 according to the present invention is shown. In method step A], Figure 2 Component 100 is equipped with a basin-shaped part closed by a cover 204. In method step B] 1302, component 100 is subjected to a transport simulation as described in the test method section. In the subsequent method step C] 1303, for at least a portion of the plurality of containers 103, the number of particles with particle sizes of at least 5 μm and at least 2 μm is determined as described in the test method section above. If the number of particles with a particle size of at least 5 μm will exceed 2.7 particles per square centimeter or the number of particles with a particle size of at least 2 μm will exceed 8.7 particles per square centimeter, then container 103 is discarded in method step D] 1304. However, for Figure 2 Component 100 is not like that. Therefore, in method step D] 1304, the pharmaceutical composition is instead filled into container 103.

[0217] Figure 14 A schematic diagram showing details of component 1400, which does not conform to the present invention, is provided. Component 1400 includes a holding device 1401 and a... Figure 1 The context describes multiple (36) containers 103. Furthermore, the holding device 1401 is designed as... Figure 1 The device 101 has a holding device, but no holding element 102. Therefore, each of the 36 containers 103 (syringes) is housed in a cup.

[0218] Figure 15 A schematic diagram showing details of another component 1400 that does not conform to the present invention is provided. Component 1400 includes a holding device 1401 and a... Figure 7 The context describes multiple (36) containers 103. The retaining device 1401 is a so-called clip-nest known in the prior art. This clip-nest includes... Figure 15 The diagram shows 36 examples of details. The spring clip nesting includes resilient retaining arms, called clips. The nesting includes two spring clips for each container 103 to be retained. The diagram shows two closed spring clips 1501 in a retaining configuration in solid lines. Identical spring clips are depicted by dashed lines as open spring clips 1502 in an open configuration. By elastically deforming the spring clips made of plastic, the spring clips can be changed from a retaining configuration to an open configuration.

[0219] Figure 16 A schematic diagram showing details of another component 1400 that does not conform to the present invention is provided. Component 1400 includes a holding device 1401 and a... Figure 7 The context describes multiple (36) containers 103. The holding device 1401 is a so-called cup nesting member known in the prior art. This nesting member includes... Figure 16The details shown are 36 instances. Thus, the 36 holes of the nesting piece from the inlet to the receiving portion are referred to as cups 1601. To allow the nesting piece to hold the containers 103, each container 103 is introduced into one of the cups 1601.

[0220] Figure 17 A schematic diagram showing details of another component 1400 that does not conform to the present invention is provided. Component 1400 includes a holding device 1401 and a plurality (36) of containers 103 serving as syringes. The syringes are held in an inverted orientation by the receiving portion of the holding device 1401.

[0221] Explanation of reference numerals in the attached figures:

[0222] 100 Components according to the invention

[0223] 101 Holding device

[0224] 102 Holding element

[0225] 103 Container

[0226] 104 matrix

[0227] 105 First Surface

[0228] 106 Another surface

[0229] 107 holes

[0230] 201 Packaging Containers

[0231] 202 Packaging container wall

[0232] 203 Inside the packaging container

[0233] 204 Cover

[0234] 205 Bottom of packaging container

[0235] 301 First end

[0236] 302 Main Body

[0237] 303 The other end

[0238] 304 discharge port

[0239] 305 Luer connector protrusion

[0240] 306 Plug

[0241] 307 container wall

[0242] 308 Inside the container

[0243] 309 Edge

[0244] 310 Another hole

[0245] 311 plunger

[0246] 401 Retaining element in the structure

[0247] 402 Release the retaining element in the structure

[0248] 801 Stepped protrusions

[0249] 901 flange

[0250] 902 Neck

[0251] 903 Shoulder

[0252] 904 Root

[0253] 905 Upright Base

[0254] 1100 Method for preparing the components of the present invention according to the present invention

[0255] 1101 Method and Steps A)

[0256] 1102 Method and Step B)

[0257] 1103 Method and Step C)

[0258] 1104 Method and Steps D)

[0259] 1105 Method and Steps E)

[0260] 1106 Method and Steps F)

[0261] 1200 includes the method according to the invention for filling containers with a pharmaceutical composition.

[0262] 1201 Method Step A.

[0263] 1202 Method Step B.

[0264] 1300 includes the method according to the invention for shaking the components of the invention and determining the particle load.

[0265] 1301 Method and Steps A]

[0266] 1302 Method and Steps B]

[0267] 1303 Method and Steps C]

[0268] 1304 Method and Steps D]

[0269] 1400 Details of components not conforming to the present invention

[0270] 1401 Holding device that does not conform to the present invention

[0271] 1501 Closed spring clip

[0272] 1502 Open the spring clip

[0273] 1601 cups

Claims

1. An assembly (100) of a nested plurality of pharmaceutical or cosmetic packaging containers, the assembly comprising a) a holding device (101) comprising a plurality of holding elements (102), and b) a plurality of containers (103); wherein each container (103) of the plurality of containers (103) comprises a container wall (307) at least partially surrounding a container interior (308), wherein the container wall (307) has an outer surface facing away from the container interior (308); wherein each container (103) of the plurality of containers (103) is detachably held by at least one of the holding elements (102) in contact with the outer surface of the container wall (307) of the respective container (103) of the plurality of containers (103); immediately after a transport simulation of the assembly (100), the number of particles having a particle size of at least 5 pm on the outer surface of all containers (103) of the plurality of containers (103) does not exceed 2.7 particles per square centimeter of the sum of the surface area of the outer surface of all containers (103) of the plurality of containers (103); wherein the transport simulation consists of a rotational plane drop test and a random vibration test successively in this order. wherein immediately after a transport simulation of the assembly (100), the number of particles having a particle size of at least 2 pm on the outer surface of all containers (103) of the plurality of containers (103) does not exceed 8.7 particles per square centimeter of the sum of the surface area of the outer surface of all containers (103) of the plurality of containers (103). the holding device (101) comprises at least one base body (104); 2. The assembly (100) according to claim 1, wherein wherein the at least one base body (104) comprises the holding elements (102), or the holding elements (102) of the plurality of holding elements (102) are arranged at the at least one base body (104).

3. The assembly (100) of claim 1, wherein, the at least one base body (104) comprises a plurality of holes (107) in a first surface (105); wherein each container (103) of the plurality of containers (103) extends at least through the first surface (105) into one of the plurality of holes (107).

4. The assembly (100) according to claim 3, wherein each container (103) of the plurality of containers (103) is detachably held by at least one holding element (102) in a form- or friction- or combination fit with the outer surface of the container wall (307) of the respective container (103) of the plurality of containers (103). the assembly (100) further comprises a packaging container (201); 5. The assembly (100) according to any one of claims 1 to 4, wherein, wherein the packaging container (201) comprises a packaging container wall (202) at least partially surrounding a packaging container interior (203); 6. The assembly (100) according to any one of claims 1 to 4, wherein wherein the holding device (101) and the containers (103) are arranged in the packaging container interior (203).

7. The assembly (100) according to claim 6, wherein the packaging container (201) is closed by a lid (204) joined to the packaging container (201), ​ ​ and / or The assembly (100) further comprises an outer packaging, wherein the packaging container (201) is arranged in the outer packaging, and / or The container (103) has been decontaminated.

8. The assembly (100) according to claim 7, wherein the assembly (100) further comprises a closed outer packaging, and / or the container (103) has been sterilized.

9. The assembly (100) according to any one of claims 1 to 4, wherein, The containers (103) of the plurality of containers (103) are packaging containers for pharmaceutical or cosmetic packaging items or both.

10. The assembly (100) according to any one of claims 1 to 4, wherein, Each container (103) of the plurality of containers (103) comprises in the following order a. a first end (301) comprising a discharge aperture (304), b. a body portion (302), and c. a further end (303).

11. The assembly (100) according to claim 10, wherein The further end (303) of the containers (103) of the plurality of containers (103) faces the bottom (205) of the packaging container (201).

12. The assembly (100) according to any one of claims 1 to 4, wherein, The containers (103) are selected from the group consisting of at least one of a vial, a syringe, a cartridge, and an ampoule.

13. The assembly (100) according to any one of claims 1 to 4, wherein, For each container (103) of the plurality of containers (103), the container wall (307) comprises glass or a polymer, wherein the polymer is a cyclic olefin copolymer, or a cyclic olefin polymer, or a mixture thereof, wherein the type of glass is selected from the group consisting of at least one of: a borosilicate glass; an aluminosilicate glass; and fused quartz.

14. The assembly (100) according to claim 13, wherein the borosilicate glass comprises Type I glass.

15. A method (1100) for producing the assembly (100) according to any one of claims 1 to 14, the method comprising the following method steps A) providing I) the holding device (101), and II) the plurality of containers (103); B) loading the holding device (101) with the containers (103) of the plurality of containers (103) such that each container (103) of the plurality of containers (103) is held detachably by at least one of the holding elements (102) by contact of the outer surface of the container wall (307) of the respective container (103) of the plurality of containers (103) with the at least one holding element (102).

16. A method (1200) for filling containers, the method comprising the following method steps A. providing the assembly (100) according to any one of claims 1 to 14; B. filling at least some of the containers (103) of the plurality of containers (103) with a pharmaceutical composition or a cosmetic composition or both.

17. Use of the assembly (100) according to any one of claims 1 to 14 for storing or transporting at least some of the containers (103) of the plurality of containers (103).

18. Use of a filling machine for filling at least some of the containers (103) of the plurality of containers (103) of the assembly (100) according to any one of claims 1 to 14 with a pharmaceutical composition or a cosmetic composition or both.

Images