Freeze-drying container

Abstract

Freeze-drying container comprising a dimensionally stable tray (1) for receiving the product to be freeze-dried, with a filling opening, preferably in the form of a connecting nozzle (5), for filling the product to be freeze-dried, preferably in the form of an aqueous product solution or suspension, wherein the dimensionally stable tray (1) has a flange (2) surrounding an access opening (1b), preferably a flat flange, and wherein a water vapor-permeable cover (3) is attached or attachable to the flange (2) such that it closes the access opening (1b). The water vapor-permeable cover (3) is furthermore detachably attached or attachable to the flange such that it can be removed from the flange (2) without damage or residue in order to expose the access opening (1b).

Description

[0001] The present application relates to a container for freeze-drying a product, preferably under sterile conditions.

[0002] In freeze-drying (also called "lyophilization") of an aqueous product solution or suspension, most of the water is removed by direct sublimation from a solid (ice) to a gaseous (water vapor) phase.

[0003] Freeze-drying of pharmaceutical products is generally carried out under sterile conditions to prevent bacterial or other contamination. Similar conditions apply if the freeze-dried product needs to be sealed, for example, because it is potentially hazardous.

[0004] Conventional freeze-drying is carried out in a pharmaceutical cleanroom with an HVAC air supply. The room must be kept extremely clean and regularly tested for particle and microbial counts.

[0005] The prior art includes a number of freeze-drying containers into which the product to be freeze-dried, preferably in the form of an aqueous product solution or suspension, is placed and introduced into a freeze-drying system. US 5,309,649 A describes a method and a container for freeze-drying under sterile conditions. In this method, the freeze-drying of a bulk product takes place in a bag, tube, or trough that consists partly of synthetic resin and partly of a hydrophobic, porous membrane that is impermeable to microorganisms and permeable to water vapor. These components are hermetically and tightly sealed at the edges by welding or bonding.From EP 2 157 387 A1, a generic container for the lyophilization of a product is known, comprising a dimensionally stable and non-folding, open-ended polypropylene plastic tray with a circumferential, flat rim or flange projecting outwards, and an upper wall completely closing the opening of the tray. This upper wall has a vapor-permeable and bacteria-impermeable polypropylene membrane and is attached to the circumferential flange by welding or gluing. The container also includes a separate, impermeable snap-on lid that covers the upper wall and the membrane for protection and is detachably attached to the circumferential rim.The snap-on lid can be positioned in a first, upper position, where sterilization, filling with the product to be freeze-dried, and freeze-drying take place, and in a second, lower position, where it is in contact with the surrounding rim and can be welded to it to create a permanent connection and seal the opening of the tray. One side wall of the tray is provided with one or more connections or ports for filling and removing the product to be freeze-dried.

[0006] Another example of a container for use in sterile freeze-drying is the LYOGUARDO tray (WL Gore and Associates, Livingston, UK). The tray's top is made of a GORE-TEX® membrane of expanded PTFE (polytetrafluoroethylene), specifically designed for lyophilization. The membrane and tray are thermally welded together, with the tray having a thin, flexible bottom that fits snugly against the drying tray to ensure efficient heat transfer. A protruding filling opening in one corner of the tray allows for the addition of the liquid product to be freeze-dried. For long-term storage of the freeze-dried product in the LYOGUARDO tray, each tray must be placed in a foil bag to prevent degradation of the dried product due to ambient humidity, oxygen, or carbon dioxide.

[0007] WO 2006 / 013360 A1 discloses a container for freeze-drying a product, comprising a tray, a lid, and a membrane. The lid and tray interact to form a hermetic seal between them, and the lid can move relative to the tray to seal vials placed upright in the tray. The membrane is permeable to water vapor and atmospheric gases, allowing vapor molecules to escape the container through the membrane. The hermetic seal is maintained during the movement of the lid relative to the tray. In one embodiment, a seal is clamped over the entire upper rim of the tray. In another embodiment, a seal is placed around the upper and outer side of the tray, similar to a thick rubber band. A groove or ridge on the outside of the tray holds the seal in place when the lid is pressed down.The exact type of seal depends on the conditions of the freeze-drying cycle and the sterilization process, for example, if the seal must withstand temperatures as low as -50 degrees Celsius. The membrane can form part or all of one or more lids, bottoms, and / or walls. If the membrane forms the entire lid, it is preferably rigid enough to allow the vials to be sealed when compressed between the trays of the freeze-drying unit. The membrane can also cover one or more holes in the lid or container (e.g., in the top, side walls, or bottom of the container) that allow the free passage of water vapor and atmospheric gases from the container, and is welded to the inner surface of the lid for this purpose.

[0008] One disadvantage of tightly sealed, especially welded, containers is that the freeze-dried material can only be accessed for removal from the container either through a relatively small filling opening, so that a relatively large residual amount of expensive end material remains in the container, especially in the corners, or the container has to be cut open for complete emptying, which is generally not permissible due to possible contamination of the end material.

[0009] It is therefore an object of the invention to propose a container for freeze-drying a product that can be manufactured cost-effectively and with which a higher yield of end material can be achieved or complete emptying can be achieved without an increased risk of contamination.

[0010] The invention proposes a container for freeze-drying a product with the features of claim 1. Preferred embodiments are specified in the dependent claims.

[0011] The invention relates in particular to a freeze-drying container comprising a dimensionally stable tray for receiving freeze-dried material, with a filling opening, preferably in the form of a connecting nozzle, for filling the freeze-dried material, preferably in the form of an aqueous product solution or suspension, wherein the dimensionally stable tray has a flange surrounding an access opening, preferably a flat flange, and wherein a water vapor-permeable cover is attached or can be attached to the flange by an adhesive in such a way that it closes the access opening. The container according to the invention is characterized in that the water vapor-permeable cover is detachably attached or can be attached to the flange in such a way that it can be removed from the flange without damage in order to expose the access opening.

[0012] The invention is based on the fundamental idea of ​​providing a stable tray for freeze-drying goods, which has a relatively large access opening on one side. This opening can be detachably closed or sealed by the water vapor-permeable cover, for example, by allowing the cover to be removed without damage or residue, similar to a snap-on lid. This allows the access opening to be practically completely exposed, providing easy and unobstructed access to the interior of the tray. As a result, the expensive end product can be easily and completely removed after freeze-drying, and the container can be completely emptied without any risk of soiling or contamination of the end product.

[0013] Furthermore, the dimensionally stable tray allows for safe and reliable handling even with protective clothing in a cleanroom environment, and the cover, which remains sealed until removal, prevents unintentional spillage of the freeze-dried product.

[0014] The connection of the water vapor-permeable cover and the shell by a detachable, non-destructive connection, preferably a positive-locking connection, preferably in the form of a snap-fit ​​connection, which is detachably or mechanically fastened to the flange, also allows the selection of suitable covers according to material and porosity for the respective application, even without having to resort to PFAS. The complete, non-destructive, and, if necessary, residue-free separation of the cover and shell at the positive-locking mechanical connection also facilitates the material-separated disposal of the components after the process and, if necessary, reuse, for example, of the stable shell after thermal treatment in an autoclave and / or sterilization by gamma radiation, without the need to remove any residue from the cover beforehand.The flat design of the flange increases the stiffness of the shell, which is helpful for the mechanical separation of the cover and shell, and creates a sealing contact surface between the cover and shell, reducing the risk of potentially unintentional leakage due to partial leakage or spillage during handling when opening due to excessive deformation.

[0015] Preferably, the water vapor-permeable cover comprises a textile structure, such as a woven fabric and / or a membrane and / or a film, which covers at least 50% of the area covering the access opening. The use of the textile structure and / or the membrane and / or the film opens up a wide selection of fabrics and materials with varying porosities. However, the invention is not limited to purely textile structures; a membrane and / or film made of PTFE, ePTFE, or PFAS-free materials with the desired porosity and vapor permeability, with or without fabric reinforcement, can also be used. For the purposes of the invention, a textile structure can be understood to be a woven fabric, but also a nonwoven fabric, knitted fabric, or similar structure.

[0016] The cover can have a circumferential edge banding designed for detachable attachment to the flange, preferably in the form of a snap-fit ​​connection and without the use of adhesive or a weld that can only be broken by destruction. The edge banding is preferably integrally molded or cast into the textile fabric and / or membrane and / or film, for example, using an in-mold process. The edge banding can provide the textile fabric (and / or membrane and / or film) with the necessary reinforcement of strength, stiffness, and, if necessary, density to create the sealing, yet detachable, connection between the cover and the flange of the shell and to allow the cover to be removed as a whole without damage or tearing, even if the textile fabric or membrane / film is relatively thin and not particularly tear-resistant.

[0017] To facilitate the removal of the cover, the edge trim can extend beyond the flange in sections, or a type of grip tab can be integrally formed on the edge trim to allow the cover to be gripped and removed from the flange, if necessary with a suitable tool, at a defined angle and with a defined pulling force.

[0018] The surrounding edge banding can be made of an elastic polymer or elastomer, for example, soft polypropylene or polyamide, silicone, etc.

[0019] The textile surface structure and / or the membrane and / or the film of the cover is permeable to water vapor and preferably also impermeable to bacteria and is made of a plastic material, preferably a PTFE, ePTFE or PFAS-free plastic material, in particular a polymer comprising polyetheretherketone (PEEK), polypropylene (PP), polyester or polyamide, wherein preferably, especially in the case of a woven fabric, a yarn diameter in µm is from 10 to 320 and / or a mesh opening in µm is from 5 to 1000 and / or an open screen area in % is from 1 to 70 and / or a basis weight in g / m² is from 20 to 200 and / or a fabric thickness in µm is from 30 to 585 and / or a screen fineness in the warp direction in n / cm is from 8 to 350 and / or a screen fineness in the weft direction in n / cm is from 8 to 350.

[0020] The tray preferably has a cuboid base, open on one side, preferably with a volume of 0.5 to 10 liters, and the access opening forms the open side of the tray facing a base surface. The cuboid base facilitates the arrangement and space utilization in a freeze-drying system and the most complete possible emptying and removal of the freeze-dried end product after the cover has been detached and removed.

[0021] The access opening can be bridged by one or more struts, the strut(s) preferably being formed from the same material as the flange. The struts can prevent deformation of the possibly flexible cover in an otherwise unsupported area between the flange sections, particularly in larger shells, and thus prevent unintentional detachment of the adhesive due to displacement of the cover in the edge areas.

[0022] Preferably, the cover and the tray are made of the same base material, for example, polypropylene, which is preferably autoclavable and / or gamma-sterilizable. Using the same or a related material simplifies the manufacturing, processing, and, if applicable, material recycling of the components after use. By selecting a suitable sterilizable material for the tray, it can also be designed for multiple uses. If the tray is intended for single use, the choice of material can optimize recycling and proper disposal.

[0023] The filling opening, preferably the connecting nozzle, can be attached to or molded onto a side wall of the tray, preferably projecting outwards from the side wall, preferably at an angle different from the perpendicular to the side wall, preferably less than 45 degrees, and further preferably inclined towards the top of the tray. This facilitates access to the filling opening without requiring the space above the container.

[0024] Preferably, the filling opening, more preferably the connection nozzle, is detachably coupled to a supply line for the freeze-dried material via a mechanical connection, preferably in the form of a threaded or bayonet connection molded onto the connection nozzle. This ensures a quick, intuitive, defined, and leak-proof detachable connection to an external line for filling the freeze-dried material in the form of an aqueous product solution or suspension.

[0025] Preferably, the filling opening, more preferably the connection nozzle, is closed by a membrane that can be pierced or removed for filling with the freeze-dried material. For this purpose, the membrane can, for example, have a predefined opening for piercing, which can be precisely cut with a pointed object, such as a filling needle or nozzle. Until the membrane is cut, the sterility of the interior is ensured, and contamination is prevented even during temporary storage of empty containers.

[0026] Furthermore, the membrane can be designed to have a self-sealing property after being punctured. For this purpose, the membrane can be made of a rubber material, at least in the area to be punctured.

[0027] The invention is described below with reference to the drawing shown in the attached illustration. Fig. 1 A highly schematic embodiment is described. This shows: Fig. 1 a perspective partial view of the container in its closed state; Fig. 2 a side view of the container of Fig. 1 on average (although a connection nozzle for filling the freeze-dried material is omitted in this illustration); and Fig. 3 A side view of the container without a cover but with a connection port on one side wall of the container.

[0028] The container for freeze-drying shown schematically in the figures according to an exemplary embodiment comprises a dimensionally stable tray or tub 1 for receiving freeze-dried material, with a filling opening, preferably in the form of a connecting nozzle 5, for filling the freeze-dried material, preferably in the form of an aqueous product solution or suspension.

[0029] The dimensionally stable shell 1 has a flange 2, preferably flat, surrounding an access opening 1b. In the exemplary embodiment, the flange 2 defines a horizontal plane in which the access opening 1b lies, and the flange may also be inclined relative to such a plane. Furthermore, the flange projects outwards from the surrounding side walls of the container 1, and may also project outwards and be curved or angled downwards to improve mechanical engagement with the cover, which will be described later.

[0030] The container then has a cover 3 which is at least partially permeable to water vapor and which can be detachably attached to the flange 2 by a positive locking mechanism.

[0031] The connection, for example in the form of a snap-in connection 8, is fastened in such a way that it tightly seals the access opening 1b and can be removed from the flange 2 without damage or residue in order to fully release the access opening 1b of the shell 1.

[0032] The water vapor-permeable cover 3 has a textile surface structure, for example a woven fabric, which covers at least 50% of the area covering the access opening 1b. However, the cover can also be formed entirely from the textile surface structure if it is sufficiently rigid.

[0033] In the Fig. 1 It is indicated by other hatching that the textile surface structure of the water vapor-permeable cover 3 has a circumferential edge 4 designed for detachable, form-fitting attachment to the flange. This edge 4 is preferably integrally molded or cast into the textile surface structure, preferably using an in-mold process. The edge 4 thus forms a kind of reinforcement of the textile surface structure to ensure the mechanical connection to the flange and non-destructive removal. Furthermore, the material of the edge 4 can have a structure that is less porous than the textile surface structure, so that sealing at a contact surface with the flange is easier to achieve.

[0034] The edge trim 4 of the cover 3 can (not shown) extend from the circumferential edge into the surface of the cover above the access opening, segmenting it, for example in the form of a grid, to achieve overall surface stiffening. The edge trim also integrally incorporates the circumferential, form-fitting, and releasable snap-in connection 8, which, for example, engages an outer edge of the flange and can be released from the flange by manually lifting it at one end and pulling it along the circumference, as shown in Fig. 2 as indicated by an arrow. The circumferential edge 4 is preferably formed from an elastic polymer or elastomer.

[0035] The textile fabric, in particular the woven fabric, is permeable to water vapor and preferably also impermeable to bacteria and is made of a plastic material, preferably a PTFE, ePTFE or PFAS-free plastic material, in particular a polymer comprising polyetheretherketone (PEEK), polypropylene (PP), polyester or polyamide, wherein preferably a yarn diameter in µm is from 10 to 320 and / or a mesh opening in µm is from 5 to 1000 and / or an open sieve area in % is from 1 to 70 and / or a basis weight in g / m² is from 20 to 200 and / or a woven thickness in µm is from 30 to 585 and / or a sieve fineness in the warp direction in n / cm is from 8 to 350 and / or a sieve fineness in the weft direction in n / cm is from 8 to 350.

[0036] However, the invention is not limited to purely textile surface structures, but a membrane and / or film (also made of a PTFE, ePTFE or PFAS-free plastic material) with the desired porosity and vapor permeability can also be used, with or without (fabric) reinforcement.

[0037] The design of the detachable, form-fitting connection between the cover and the tray (the flange) is based on the principle that, on the one hand, the cover remains tightly sealed and securely attached under the conditions of the freeze-drying cycle and any subsequent sterilization process, and on the other hand, that the cover can be removed from the container's flange without damage after the freeze-drying process. The term "without damage" refers to both the tray and the cover, ensuring that no components of either end up in the final product or that contaminants adhering to the outside of the cover enter the tray and thus come into contact with the final product.

[0038] The tray or container 1 has a cuboid base, open on one side, preferably with a volume of 0.5 to 10 liters, and the access opening 1b forms the open side of the tray 1 facing a base surface. For example, the tray can have dimensions according to standard sizes for such production containers, for example 480 mm (width) x 240 mm (depth) x 50 mm (height) or fractions or multiples of these dimensions.

[0039] The access opening 1b can be bridged by one or more struts (not shown), wherein the strut(s) are preferably formed from the same material as the flange 2 or the shell 1 and have at least one bearing surface for the cover in the plane of the access opening 1b. This provides a support for the cover that prevents downward deflection, particularly in the case of larger container dimensions and / or less rigid covers. Attaching the cover to this strut(s) is possible, but not mandatory.

[0040] Preferably, the tray 1 is made of polypropylene and is heat-resistant to allow autoclaving and / or gamma sterilization. A particularly preferred variant is one in which both the cover 3 and the tray 1 are made of the same base material.

[0041] The filling opening for the freeze-dried material, preferably in the form of an aqueous product solution or suspension, can be designed in any shape and structure. The preferred design is the one described in Fig. 3 The illustrated variant features a filling opening designed as a connecting nozzle 5, which is attached to or integrally formed on a narrow side wall 1a of the shell 1 and projects outwards from this side wall 1a. The connecting nozzle 5 extends, at least in sections, at an angle different from the perpendicular to the side wall 1a, preferably at 45 degrees upwards and / or to the side, so that the connecting nozzle 5 is more easily accessible but does not project upwards above the plane defined by the flange 2.

[0042] For connection to an external line or other supply for the freeze-dried material, the filling opening, specifically the connection nozzle 5, can be detachably coupled to the line via a mechanical connection, preferably in the form of a threaded or bayonet connection 6 molded onto the connection nozzle. The size of the connection nozzle 5 can be based on the usual standardized sizes for fluid connections and may be, for example, ½ inch, ¾ inch or 1 inch.

[0043] To ensure the sterility of the interior of the container sealed with the cover until use or filling, the filling opening, preferably the connection nozzle 5, can be closed by a membrane which is punctureable or removable for filling with the freeze-dried material, and wherein the membrane preferably has a predefined opening for piercing. The membrane can, for example, be made of a suitable plastic or rubber material, and can be designed to have a self-sealing property after piercing.

Claims

1. Freeze-drying container comprising: a dimensionally stable tray (1) for receiving freeze-dried material, with a filling opening, preferably in the form of a connecting nozzle (5), for filling the freeze-dried material, preferably in the form of an aqueous product solution or suspension, wherein the dimensionally stable tray (1) has a flange (2) surrounding an access opening (1b), preferably a flat flange, and wherein a water vapor permeable cover (3) is attached or attachable to the flange (2) in such a way that it closes the access opening (1b), characterized by the fact that the water vapor permeable cover (3) is detachably attached or attachable to the flange in such a way that it can be removed from the flange (2) without damage in order to expose the access opening (1b).

2. Freeze-drying container according to claim 1, wherein the water vapor permeable cover (3) is detachably attached or attachable to the flange (2) by a positive-locking connection, preferably in the form of a snap-in connection (8).

3. Freeze-drying container according to claim 1 or 2, wherein the water vapor permeable cover (3) comprises a textile surface structure and / or a membrane and / or a film which covers at least 50% of the area covering the access opening (1b).

4. Freeze-drying container according to any one of claims 1 to 3, wherein the water vapor permeable cover (3) has a circumferential edge trim (4) which is designed for detachable attachment to the flange (2), preferably in the form of a snap-fit ​​connection, wherein the edge trim (4) is preferably integrally molded or cast in with the textile surface structure and / or the membrane and / or the film, preferably in an in-mold process.

5. Freeze-drying container according to claim 4, wherein the circumferential rim (4) is formed from an elastic polymer or elastomer.

6. Freeze-drying container according to any one of claims 1 to 5, wherein the textile fabric and / or the membrane and / or the film is made of plastic, preferably of PTFE, ePTFE or of PFAS-free materials, in particular of a polymer comprising polyetheretherketone (PEEK), polypropylene (PP), polyester or polyamide, wherein preferably, particularly in the case of a woven fabric, a yarn diameter in µm of 10 to 320 and / or a mesh opening in µm of 5 to 1000 and / or an open mesh area in % of 1 to 70 and / or a basis weight in g / m² 2 from 20 to 200 and / or a fabric thickness in µm from 30 to 585 and / or a sieve fineness in warp direction in n / cm from 8 to 350 and / or a sieve fineness in weft direction in n / cm from 8 to 350.

7. Freeze-drying container according to any one of claims 1 to 6, wherein the tray (1) has a cuboid, open-ended base shape, preferably with a volume of 0.5 to 10 liters, and the access opening (1b) forms the open side of the tray (1) opposite a bottom surface.

8. Freeze-drying container according to any one of claims 1 to 7, wherein the access opening (1b) is bridged by one or more struts, wherein the strut(s) is / are preferably formed of the same material as the flange (2).

9. Freeze-drying container according to any one of claims 1 to 8, wherein the cover (3) and the tray (1) are made of the same base material.

10. Freeze-drying container according to any one of claims 1 to 9, wherein the tray (1) is made of polypropylene, preferably autoclavable and / or gamma-sterilizable.

11. Freeze-drying container according to any one of claims 1 to 10, wherein the filling opening, preferably the connecting nozzle (5), is attached or formed on a side wall (1a) of the tray (1), preferably projecting outwards from the side wall (1a), preferably at an angle different from the perpendicular to the side wall (1a), preferably at 45 degrees.

12. Freeze-drying container according to any one of claims 1 to 11, wherein the filling opening, preferably the connection nozzle (5), can be detachably coupled to a supply line for the freeze-dried material via a mechanical connection, preferably in the form of a threaded or bayonet connection (6) molded onto the connection nozzle (5).

13. Freeze-drying container according to any one of claims 1 to 12, wherein the filling opening, preferably the connection nozzle (5), is closed by a membrane which is pierceable or removable for filling with the freeze-dried material, and wherein the membrane preferably has a predefined opening for piercing.

14. Freeze-drying container according to claim 13, wherein the membrane is designed to have a self-sealing property after being punctured.

15. Freeze-drying container according to claim 13 or 14, wherein the membrane is made of a rubber material at least in the area to be penetrated.

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