EP4357709A1 - Lyophilisierungsstopfen mit einer membran - Google Patents

Lyophilisierungsstopfen mit einer membran Download PDF

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Publication number
EP4357709A1
EP4357709A1 EP22202491.1A EP22202491A EP4357709A1 EP 4357709 A1 EP4357709 A1 EP 4357709A1 EP 22202491 A EP22202491 A EP 22202491A EP 4357709 A1 EP4357709 A1 EP 4357709A1
Authority
EP
European Patent Office
Prior art keywords
stopper
water vapor
vial
permeable membrane
lyophilization
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP22202491.1A
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English (en)
French (fr)
Inventor
José Martins ASCENSAO
Francisco CARETTO
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ead Sarl
Original Assignee
Ead Sarl
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ead Sarl filed Critical Ead Sarl
Priority to EP22202491.1A priority Critical patent/EP4357709A1/de
Priority to PCT/EP2023/078781 priority patent/WO2024083794A1/en
Publication of EP4357709A1 publication Critical patent/EP4357709A1/de
Pending legal-status Critical Current

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B5/00—Drying solid materials or objects by processes not involving the application of heat
    • F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
    • F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing

Definitions

  • the present invention is directed to a lyophilization stopper comprising a water vapor-permeable membrane.
  • Lyophilization i.e. freeze-drying
  • the solvent is removed by sublimation.
  • several containment systems are known in the prior art.
  • WO 2019/012512 A1 describes a container that has been designed to protect product from contamination during lyophilization.
  • the container has at least one water vapor-permeable side through which water vapor can escape during lyophilization.
  • a container is unsuitable for long-term storage, as water can re-hydrate the product in the container in a humid environment.
  • such a container is unsuitable for easy handling, as a needle pierceable region for reconstitution is missing.
  • Vials with rubber stoppers are commonly used, wherein the stopper has a first configuration that allows the sublimation of the solvent and a second configuration for sealing the vial with the stopper.
  • the product itself may potentially be hazardous and may contaminate the process facility.
  • Such a risk of contamination is in particular worrisome for crosscontamination between batches of different products, wherein trace amounts of a first product may cross-contaminate a batch of a second product. It is, in particular for lyophilization in vials, a drawback that contamination can occur when the stopper is the above-mentioned first configuration and the vial is not yet sealed.
  • Lyophilization products are especially concerned given the need for the vial to be partially open (“pre-plugged") during the lyophilization process in order to allow the water that sublimates during the process to escape the vial.
  • the lyophilization can take several days in those products that require long freeze-drying cycles, thereby increasing the risk for contamination.
  • a stopper comprising a stopper body and a water vapor-permeable membrane.
  • this stopper allows the sublimation of solvent, such as water, during a lyophilization process while at the same time providing a barrier that lowers the risk of contamination.
  • the membrane used in the stopper of the present invention is permeable to water vapor, thereby allowing the water that sublimates during the lyophilization process to escape the vial.
  • the membrane used in the stopper of the present invention is furthermore impermeable to liquid water and impermeable to microorganisms, thereby reducing, preferably avoiding the risk of contamination such as microbiological contamination with microorganisms, such as bacteria, viruses, and fungi, in particular bacteria, of the lyophilized product.
  • the stopper of the present invention can maintain the container closure integrity (CCI) of the prior art container systems.
  • the stopper can be used with a vial for ready-to-use formulations, wherein the stopper can be pierced by a needle without interference of the water vapor-permeable membrane.
  • the invention in another aspect, relates to a kit of parts comprising the stopper of the present invention, a lyophilization container, and preferably a cap assembly.
  • the present invention relates to the use of the stopper of the present invention for lyophilization.
  • the present invention relates to a method for preparing the stopper of the present invention, comprising the steps of
  • compositions wherein the active ingredient fulfils all necessary pharmaceutical standards/monographs of the USP-NF (United States Pharmacopoeia National Formulary) or Ph. Eur. (European Pharmacopoeia) reference standard with regard to purity of the active ingredient and/or amount of pathogens and/or bacterial contamination.
  • stopper body refers to the part of the stopper of the present invention not comprising a water vapor-permeable membrane.
  • stopper generally refers to a device for closing a container or vial.
  • stopper head refers to the part of the stopper body that is configured to not be inserted into the lyophilization vial.
  • the stopper head has a larger diameter than the stopper leg and a larger diameter than the vial opening.
  • stopper leg refers to the part of the stopper body that is configured to be pushed into the lyophilization vial.
  • the stopper leg preferably protrudes essentially orthogonal to the main surface area of the stopper head.
  • water vapor-permeable refers to a water vapor permeability of 1000 g/m 2 /24 h or more.
  • essentially orthogonal refers to an angle of 70° to 110°.
  • essentially parallel refers to an angle of -20° to +20°.
  • wt.-% refers to the amount of the respective ingredient by weight based on the total amount of the element it refers to, unless noted otherwise.
  • a stopper leg means one stopper leg or more than one stopper leg.
  • vent area is to be understood as the area on the outer surface of the stopper of a vent passageway.
  • the vent passageway is a passageway for gas that goes through the stopper and is used for venting gas during the lyophilization process.
  • the vial is "pre-plugged" when the stopper is not completely inserted into the vial. With conventional stoppers, this configuration leaves vent areas allowing water vapor resulting from sublimation to escape the vial during lyophilization.
  • the stopper is a lyophilization stopper.
  • the stopper is a stopper for lyophilization, i.e. the stopper is for sealing and venting a lyophilization container, preferably a vial.
  • the stopper of the present invention is a vial stopper.
  • the stopper of the present invention is a two-legged stopper, a three-legged stopper or an Igloo stopper.
  • These stoppers are commercially available, e.g. from West Pharmaceutical Services Inc. or DWK life Sciences Co. Ltd.
  • a two-legged stopper of the prior art is schematically depicted in Figures 1 and 2 .
  • Igloo stoppers comprise a vent area comprising one vent portion through which gas can be removed during the lyophilization process.
  • Two-legged stoppers comprise a vent area consisting of two vent portions through which gas can be removed during the lyophilization process.
  • Three-legged stopper comprise a vent area consisting of three vent portions through which gas can be removed during the lyophilization process. These stoppers are typically sold having an outer diameter of the stopper leg of e.g. 12 mm, 13 mm, 15 mm or 20 mm. These stoppers are advantageous due to the large vent area that allows efficient and fast lyophilization. In addition, such stoppers are compatible with automated loading unloading systems (ALUS). The compatibility with automated systems, such as ALUS, is beneficial, since the use of automated systems increases production efficiency and further minimizes the risk of contamination before and after freeze-drying.
  • ALUS automated loading unloading systems
  • the stopper of the present invention is a bunker stopper.
  • a bunker stopper is schematically depicted in Figure 7 .
  • Bunker stoppers comprise a vent area on the stopper leg, preferably near the stopper head. In the present invention, the vent area is completely covered by the water vapor-permeable membrane.
  • the bunker stopper In the pre-plugged state, the bunker stopper is configured so that the water vapor-permeable membrane is not in the vial and is not in contact with the surface of the vial. After lyophilization, the bunker stopper is fully inserted so that the vent area and the water vapor-permeable membrane is inside the vial and the vial is sealed by the stopper.
  • vent area is near the stopper head to minimize the amount of surface exposed to the outside in the pre-plugged state to further minimize the risk of contamination.
  • This configuration is particularly preferred, as there is even less risk of contamination, as there is no contact point between the water vapor-permeable membrane and the vial's surface in the pre-plugged state.
  • the bunker stopper is configured in that the water-vapor permeable membrane is essentially orthogonal to the stopper head and/or the needle penetration area.
  • the stopper body comprises a stopper head.
  • the stopper head is configured to prevent the stopper from sliding or falling into a vial.
  • the stopper head comprises a main surface area. Said main surface area is preferably circular.
  • the stopper head preferably comprises a needle penetration region, i.e. a needle pierceable area.
  • the needle penetration area is configured so that a needle can penetrate through the stopper. This region is preferably centrally located on the stopper head, i.e. the stopper comprises a centrally located needle penetration region. This is useful for reconstituting the lyophilized product and emptying the vial without removing the stopper.
  • the stopper comprises a vent passageway for venting gas during the lyophilization process.
  • the stopper body may further comprise a stopper leg that protrudes essentially orthogonal to the main surface area of the stopper head.
  • the leg is configured to be inserted into the vial.
  • the leg is configured to span a vent area on the outer surface of the stopper that allows gas to flow through the vent passageway through the stopper when the stopper is only partially inserted into a vial.
  • the water vapor-permeable membrane is not parallel to the main surface area of the stopper head or the needle penetration area.
  • the water vapor-permeable membrane is essentially orthogonal, i.e. horizontal, to the main surface area of the stopper head and/or the needle penetration area.
  • the water vapor-permeable membrane covers the vent passageway.
  • the water vapor-permeable membrane is placed in the path of any gas traveling through the vent passageway. It is preferred that the water vapor-permeable membrane completely or partially covers the vent area.
  • the stopper of the present invention is a lyophilization vial stopper comprising a stopper body and a water vapor-permeable membrane, wherein
  • the stopper comprises nubs and/or recesses. Nubs and/or recesses facilitate fastening of the stopper to the vial and prevent the stopper from slipping off the vial. When the stopper is inserted into the vial, the stopper needs to be in a proper position. The nubs and/or recesses prevent angled or misplaced positioning of the stopper.
  • the stopper comprises a sealing ring.
  • the sealing ring facilitates fastening of the stopper in the "open" configuration and stabilizes the legs of the stopper.
  • the sealing ring prevents microcanals between the stopper and the vial from forming in the open configuration and helps to stabilize the legs during the insertion of the stopper into a vial.
  • the sealing band comprises preferably the same rubber as the stopper.
  • the stopper does not comprise any moving parts.
  • the absence of moving parts leads to a more stable and reliable stopper.
  • the absence of moving parts decreases the probability of errors due to malfunctioning of the moving parts during the lyophilization process. As many lyophilized products are complex molecules that are difficult to manufacture, even a small decrease in errors during the lyophilization process results in substantial cost savings.
  • the stopper of the present invention comprises a stopper body that is laminated with a fluoropolymer or a silicone polymer.
  • a laminated stopper can reduce the migration of leachables from the stopper and can facilitate the insertion of the stopper into the vial.
  • the water vapor-permeable membrane comprises expanded polytetrafluoroethylene (ePTFE) and/or a polymer selected from the group consisting of polyether esters, polyether amides, polyether urethanes, and mixtures thereof. It is preferred that the water vapor-permeable membrane comprises ePTFE. In an embodiment, the membrane comprises 50 to 100 wt.-% of ePTFE, preferably 70 to 100 wt.-% of ePTFE, and more preferably 90 to 100 wt.-% of ePTFE. In an embodiment, the water vapor-permeable membrane consists of ePTFE.
  • Extractables are chemical entities that may be released from container systems under stressed conditions with various solvents.
  • Leachables are chemical entities that can migrate from the container system into the drug product under standard conditions.
  • ePTFE is obtained by the steps of extrusion of a PTFE resin with a lubricant, usually a naptha solvent. After extrusion to provide a film, the film is calendared, dried to evaporate the lubricant and subsequently expanded (either uniaxially or biaxially) at elevated temperatures, to provide a ePTFE membrane.
  • a ePTFE membrane is porous. The size of the pores are larger than molecules of water molecules but significantly smaller than water droplets, thus making the ePTFE membrane water vapor-permeable but impermeable to liquid water.
  • the expanded polytetrafluoroethylene is an uniaxially expanded membrane.
  • An uniaxially expanded membrane is obtainable by calendaring in the machine direction (MD).
  • the expanded polytetrafluoroethylene is a biaxially expanded membrane.
  • a biaxial expanded membrane is obtainable by calendaring in the machine direction (MD) and in transverse or cross direction (CD).
  • the ePTFE membrane preferably has a microstructure of nodes and fibrils, wherein the fibrils connect the nodes.
  • the water vapor-permeable membrane comprises a polyether polyester copolymer or a polyester polymer. Such membranes are commercially available as Sympatex ® and Futurelight TM .
  • the water vapor-permeable membrane is a polyurethane. Suitable polyurethanes are described in US 6,790,926 B1 .
  • the water vapor-permeable membrane has a thickness of 0.1 to 500 ⁇ m, preferably of 1 to 200 ⁇ m, more preferably of 5 to 100 ⁇ m.
  • the membrane has a thickness of less than 0.1 ⁇ m, the processing can be difficult and the stability of the membrane suffers.
  • the thickness of the membrane exceeds 500 ⁇ m, the water vapor permeability may decrease leading to a less efficient lyophilization process.
  • the water vapor-permeable membrane has a water vapor permeability of 1000 to 65000 g/m 2 /24 h, preferably of 3000 to 50000 g/m 2 /24 h.
  • the water vapor permeability can be measured according to ASTM E-96-95, procedure B.
  • the water vapor-permeable membrane has a water vapor permeability of 500 to 100000 g/m 2 /24 h, of 2000 to 40000 g/m 2 /24 h or of 4000 to 20000 g/m 2 /24 h.
  • the membrane can comprise one or more layers.
  • the membrane consists of a single layer.
  • the membrane consists of a single layer and the membrane comprises 70 to 100 wt.-% expanded polytetrafluoroethylene.
  • the membrane is a multi-layer construction, comprising, two, three, four or more layers. The layers can be attached to each other by lamination.
  • the membrane comprises polyethylene, polyethylene terephthalate, and/or mixtures thereof.
  • the stopper body comprises a rubber.
  • the rubber is selected from the group consisting of natural rubber, isoprene rubber, ethylene propylene diene rubber, butyl rubber, bromobutyl rubber, chlorobutyl rubber and mixtures thereof as well as copolymers thereof.
  • the rubber stopper may be coated by a hydrophobic coating agent, such as silicone polymers or may contain a desiccant.
  • a hydrophobic coating agent such as silicone polymers or may contain a desiccant.
  • the rubber stopper is coated with a polytetrafluoroethylene (PTFE) coating. The coating is preferable on the inside of the stopper.
  • PTFE polytetrafluoroethylene
  • the stopper body comprises a filler, an accelerator, an activator, a plasticizer, a pigment, and/or a stabilizer.
  • the stopper is sterile in accordance with the European Pharmacopoeia 5.1.1, edition 10.0, 2019.
  • the invention relates to a kit of parts comprising the stopper of the present invention, a lyophilization container, and preferably a cap assembly.
  • the lyophilization container is a vial.
  • the vial can be a plastic or a glass vial. Examples for glass are soda-lime glass and borosilicate.
  • the vial has a hole opening with an inner diameter of 5 to 100 mm, preferably of 10 to 50 mm.
  • the stopper has an outer diameter that is slightly larger of the inner diameter of the vial.
  • the outer diameter of the stopper refers to the diameter of the portion of the stopper that is inserted into the vial, i.e.
  • the outer diameter does not refer to the diameter of the stopper head.
  • the outer diameter of the stopper refers to the outer diameter of the stopper legs, i.e. the portion of the stopper that is inserted into the vial.
  • a rubber stopper with an outer diameter of e.g. 13 mm can be used.
  • the stopper is configured to have
  • the water vapor can vent through the vent area.
  • the vent area is completely covered by the water vapor-permeable membrane.
  • This configuration is used during the lyophilization process. Usually, this configuration is achieved by inserting the stopper into an intermediate position into the vial.
  • the vial is hermetically sealed by the stopper. This position is used for storage. Usually, this configuration is achieved by inserting the stopper further into the vial until the stopper head touches the vial.
  • the water vapor-permeable membrane is configured to substantially only cover the area on the outer surface of the stopper in the first position that allows water vapor through, i.e. the water vapor-permeable membrane covers the opening of the stopper body (the vent area), when inserted into the vial.
  • the water vapor-permeable membrane is not coated continuously over the surface of the stopper body or the stopper leg.
  • the stopper is configured so that the stopper body can be pierced to reconstitute the lyophilized product by a needle without piercing the water vapor-permeable membrane.
  • the water-permeable membrane is not connected in such a way to the stopper body that the water vapor-permeable membrane can be pierced by a needle.
  • the water-permeable membrane is not essentially parallel to the main surface area of the stopper head.
  • Such a configuration, as depicted in Figures 3 , 4, and 6 is preferred, as the membrane is not damaged by the piercing with the needle.
  • a thin membrane can be used and the stopper can be re-used.
  • the water vapor-permeable membrane is parallel to the main surface area of the stopper head and is pierced when the lyophilized product is reconstituted.
  • the membrane may be damaged, in particular if the membrane is too thin.
  • this configuration wherein the water-permeable membrane is not parallel to the main surface area of the stopper head, improves safety during reconstitution.
  • the vent area that is covered by the water vapor-permeable membrane has a large surface area and therefore results in a time-efficient lyophilization process. It is preferred that the vent area has a surface of 0.01 cm 2 to 10 cm 2 , of 0.05 cm 2 to 5 cm 2 , of 0.1 cm 2 to 5 cm 2 , of 0.25 cm 2 to 5 cm 2 , of 0.5 cm 2 to 5 cm 2 , of 0.75 cm 2 to 5 cm 2 , of 1 cm 2 to 4 cm 2 , or of 1.5 cm 2 to 3 cm 2 . It is to be understood that the surface area of the vent area corresponds to the surface of the membrane which completely covers the vent area.
  • the membrane of the present invention likewise has a surface area of preferably 0.01 cm 2 to 10 cm 2 , of 0.05 cm 2 to 5 cm 2 , of 0.1 cm 2 to 5 cm 2 , of 0.25 cm 2 to 5 cm 2 , of 0.5 cm 2 to 5 cm 2 , of 0.75 cm 2 to 5 cm 2 , of 1 cm 2 to 4 cm 2 , or of 1.5 cm 2 to 3 cm 2
  • the kit of parts of the present invention comprises a cap system.
  • the cap system also known as crimp seal, can comprise a metal seal, such as aluminum, and preferably a polymer button, and is configured to surround both the stopper and a neck of the vial in a sealed position.
  • the cap system comprises a plastic cap, the plastic cap preferably comprising polypropylene.
  • the cap comprises a polymer selected from the group of PE (polyethylene), PET (polyethylene terephthalate), PETG (polyethylene terephthalate glycol), PEHD (polyethylene high-density), PP (polypropylene), ABS (acrylonitrile butadiene styrene) polymer, and mixtures thereof.
  • Cap systems act as an additional seal (the contact between stopper and vial acting as the primary seal) and are advantageous for further sealing the vial and increasing the container closure integrity (CCI). The cap system can then be removed prior to use.
  • the stopper of the present invention is used for lyophilization.
  • the stopper is used to lyophilize a pharmaceutically active agent or a pharmaceutical composition, which typically comprises one or more pharmaceutically acceptable excipients besides the pharmaceutically active agent(s).
  • the use of the stopper comprises the step of filling a pharmaceutical composition in a syringe, cartridge, vial or container.
  • the stopper can then be inserted into the syringe, cartridge, vial or container so that gas can vent through the vent passageway.
  • the syringe, cartridge, vial or container is hermetically sealed with the stopper.
  • a cap system is additionally used for sealing the syringe, cartridge, vial or container.
  • the pharmaceutical composition can be reconstituted with solvent prior to use. This allows for the administration by intravenous infusion or injection as well as subcutaneous injection. However, it is also possible to provide the pharmaceutical composition as a suspension which is used for subcutaneous injection.
  • the invention relates to a method for preparing the stopper of the present invention, the method comprising the steps of
  • the method further comprises the step of (c) sterilization of the stopper by gamma ray irradiation, by water vapor sterilization or by chemical sterilization, preferably by using chemical sterilization with ethylene oxide.
  • the stopper and/or the pharmaceutical composition is sterile in accordance with the European Pharmacopoeia 5.1.1, edition 10.0, 2019 .
  • the composition is sterile, i.e. it contains less than 10 -4 wt.-% of nonsterile material, such as microbial contamination. Sterility of the composition can be ensured by a number of processes, such as thermal, chemical, and radiation steps.
  • the stopper complies with the good manufacturing practice (GMP) standard for primary packaging materials for medicinal products DIN EN ISO 15378. It is preferred that all steps are performed under aseptic conditions.
  • GMP good manufacturing practice
  • the stopper is a stopper for a vial, preferably a glass or plastic vial. Any composition contained in the vial may be removed from the vial by puncturing the stopper with a needle.
  • stoppers according to the present invention comprising an ePTFE membrane with conventional stoppers (not comprising a membrane) in terms of their ability to evacuate different volumes of water during a freeze-drying cycle.
  • Vials were filled with different filling volume of water (2 mL and 5 mL) and stoppered with a stopper in accordance with the present invention or without a stopper.
  • the vials were then lyophilized using the following freeze-drying cycle, launched in the 100ST freeze dryer (Table 1): Table 1: Cycle for lyophilization Phase Temperature [°C] Vacuum [mBar] Time [hours:minutes] Freezing -50.0 --- 0:10 Freezing -50.0 --- 3:0 Condenser preparation --- --- 0:10 Primary drying 50.0 0.200 0:10 Primary drying 50.0 0.200 10:0 Secondary drying 50.0 --- 0:1 Secondary drying 50.0 --- 1:0
  • Vials were filled with different filling volume of water (2 mL and 5 mL) and either (i) stoppered with a stopper in accordance with the present invention, comprising an ePTFE membrane covering the vent area using different surface areas between 3.14 mm 2 and 176.63 mm 2 (Vials 1-7, 11-17); or (ii) not stoppered and used as open vials without a stopper (Vials 8-10, 18-20).
  • stoppers of the present invention have a similar capacity to evacuate water than open vials.
  • stoppers of the present invention offer the additional advantage that it will not be necessary to modify established freeze-drying cycles for existing pharmaceutical products, at the same time dramatically reducing the risk of microbiological contamination.
EP22202491.1A 2022-10-19 2022-10-19 Lyophilisierungsstopfen mit einer membran Pending EP4357709A1 (de)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP22202491.1A EP4357709A1 (de) 2022-10-19 2022-10-19 Lyophilisierungsstopfen mit einer membran
PCT/EP2023/078781 WO2024083794A1 (en) 2022-10-19 2023-10-17 Lyophilization stopper comprising a membrane

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP22202491.1A EP4357709A1 (de) 2022-10-19 2022-10-19 Lyophilisierungsstopfen mit einer membran

Publications (1)

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EP4357709A1 true EP4357709A1 (de) 2024-04-24

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EP22202491.1A Pending EP4357709A1 (de) 2022-10-19 2022-10-19 Lyophilisierungsstopfen mit einer membran

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EP (1) EP4357709A1 (de)
WO (1) WO2024083794A1 (de)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5522155A (en) * 1994-08-19 1996-06-04 W. L. Gore & Associates, Inc. Vented vial method of minimizing contamination of freeze-dried products
US5596814A (en) * 1995-11-06 1997-01-28 W. L. Gore & Associates, Inc. Vented vial stopper for processing freeze-dried products
US6790926B1 (en) 1998-10-21 2004-09-14 Sympatex Technologies Gmbh Water vapor permeable thermoplastic polyurethane film
WO2007127286A2 (en) * 2006-04-24 2007-11-08 Medical Instill Technologies, Inc. Needle penetrable and laser resealable lyophilization device and related method
US20090175315A1 (en) * 2005-04-26 2009-07-09 John Jeffrey Schwegman Wireless temperature sensing system for lyophilization processes
WO2013164422A2 (de) * 2012-05-03 2013-11-07 Schott Ag Verfahren und vorrichtung zur behandlung von behältern und in diesen aufbewahrten substanzen für medizinische, pharmazeutische oder kosmetische anwendungen
WO2019012512A1 (en) 2017-07-14 2019-01-17 4D Pharma León, S.L.U. PRODUCT LYOPHILIZATION METHOD

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5522155A (en) * 1994-08-19 1996-06-04 W. L. Gore & Associates, Inc. Vented vial method of minimizing contamination of freeze-dried products
US5596814A (en) * 1995-11-06 1997-01-28 W. L. Gore & Associates, Inc. Vented vial stopper for processing freeze-dried products
US6790926B1 (en) 1998-10-21 2004-09-14 Sympatex Technologies Gmbh Water vapor permeable thermoplastic polyurethane film
US20090175315A1 (en) * 2005-04-26 2009-07-09 John Jeffrey Schwegman Wireless temperature sensing system for lyophilization processes
WO2007127286A2 (en) * 2006-04-24 2007-11-08 Medical Instill Technologies, Inc. Needle penetrable and laser resealable lyophilization device and related method
WO2013164422A2 (de) * 2012-05-03 2013-11-07 Schott Ag Verfahren und vorrichtung zur behandlung von behältern und in diesen aufbewahrten substanzen für medizinische, pharmazeutische oder kosmetische anwendungen
WO2019012512A1 (en) 2017-07-14 2019-01-17 4D Pharma León, S.L.U. PRODUCT LYOPHILIZATION METHOD

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"European Pharmacopoeia", 2019

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