US20150107195A1 - Container and Method of Manufacture of Container - Google Patents
Container and Method of Manufacture of Container Download PDFInfo
- Publication number
- US20150107195A1 US20150107195A1 US14/119,280 US201114119280A US2015107195A1 US 20150107195 A1 US20150107195 A1 US 20150107195A1 US 201114119280 A US201114119280 A US 201114119280A US 2015107195 A1 US2015107195 A1 US 2015107195A1
- Authority
- US
- United States
- Prior art keywords
- closure
- container
- piston
- active agents
- recess
- 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.)
- Abandoned
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 title claims description 25
- 239000013543 active substance Substances 0.000 claims abstract description 73
- 239000003085 diluting agent Substances 0.000 claims abstract description 39
- 229960005486 vaccine Drugs 0.000 claims description 20
- 238000007789 sealing Methods 0.000 claims description 18
- 238000004108 freeze drying Methods 0.000 claims description 7
- 230000000717 retained effect Effects 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 18
- 238000003860 storage Methods 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000011109 contamination Methods 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/202—Separating means
- A61J1/2027—Separating means having frangible parts
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B3/00—Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans, or jars
- B65B3/003—Filling medical containers such as ampoules, vials, syringes or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/1412—Containers with closing means, e.g. caps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2003—Accessories used in combination with means for transfer or mixing of fluids, e.g. for activating fluid flow, separating fluids, filtering fluid or venting
- A61J1/2068—Venting means
- A61J1/2072—Venting means for internal venting
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2093—Containers having several compartments for products to be mixed
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B29/00—Packaging of materials presenting special problems
- B65B29/10—Packaging two or more different substances isolated from one another in the package but capable of being mixed without opening the package, e.g. forming packages containing a resin and hardener isolated by a frangible partition
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B55/00—Preserving, protecting or purifying packages or package contents in association with packaging
- B65B55/02—Sterilising, e.g. of complete packages
- B65B55/04—Sterilising wrappers or receptacles prior to, or during, packaging
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B63/00—Auxiliary devices, not otherwise provided for, for operating on articles or materials to be packaged
- B65B63/08—Auxiliary devices, not otherwise provided for, for operating on articles or materials to be packaged for heating or cooling articles or materials to facilitate packaging
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B7/00—Closing containers or receptacles after filling
- B65B7/16—Closing semi-rigid or rigid containers or receptacles not deformed by, or not taking-up shape of, contents, e.g. boxes or cartons
- B65B7/28—Closing semi-rigid or rigid containers or receptacles not deformed by, or not taking-up shape of, contents, e.g. boxes or cartons by applying separate preformed closures, e.g. lids, covers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D51/00—Closures not otherwise provided for
- B65D51/24—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes
- B65D51/241—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes provided with freeze-drying means
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D51/00—Closures not otherwise provided for
- B65D51/24—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes
- B65D51/28—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes with auxiliary containers for additional articles or materials
- B65D51/2807—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes with auxiliary containers for additional articles or materials the closure presenting means for placing the additional articles or materials in contact with the main contents by acting on a part of the closure without removing the closure, e.g. by pushing down, pulling up, rotating or turning a part of the closure, or upon initial opening of the container
- B65D51/2814—Closures not otherwise provided for combined or co-operating with auxiliary devices for non-closing purposes with auxiliary containers for additional articles or materials the closure presenting means for placing the additional articles or materials in contact with the main contents by acting on a part of the closure without removing the closure, e.g. by pushing down, pulling up, rotating or turning a part of the closure, or upon initial opening of the container the additional article or materials being released by piercing, cutting or tearing an element enclosing it
Definitions
- Methods of manufacturing sterile liquid containers and sterile liquid containers more specifically methods of manufacturing vials and vials.
- the one or more active agents is an unstable species in solution
- the one or more active agents and the diluent are often stored separately in two sterile storage units before administration.
- the one or more active agents and the diluent are stored separately and combined immediately prior to administration, there is a risk of contamination of the medicament. To ensure that contamination does not occur, the combination of the one or more active agents and diluent is carried out using a lengthy and time consuming procedure.
- a method of manufacturing a pre-loaded container for use in dispensing one or more active agents comprising the steps of;
- the step of sealing the closure comprises sealedly mounting a sealing element comprising a piston.
- the piston may comprise a hollow column retained within a cylinder in the closure.
- the piston may comprise apertures suitable for ventilating the recess of the closure during the step of lyophilisation.
- the step of sealing the closure may seal the apertures of the piston.
- the piston may comprise a deformable feature extending from the outer surface of the closure such that deformation of the piston by the application of pressure to the said outer surface releases the lyophilised one or more active agents from the closure into the diluent of the container.
- lyophilised active agent and diluent are stored in separate sterile containers. Therefore, for any one active agent to be available for use, two components must be sourced and stored.
- the active agent is to be used, the diluent is extracted from its packaging using a syringe and the syringe is then inserted into the packaging of the active agent. The diluent is then added to solubilise the active agent.
- the active agent packaging must then be agitated to ensure that the active agent is fully dissolved to reconstitute the active agent into its solubilised form. Finally, the solution is then drawn into the syringe ready for use.
- container made according to the above method allows the active agent and diluent to be stored as a single entity, conserving space.
- the process of reconstituting the active agent is greatly reduced to a two step process of breaking the closure to allow the lyophilised active agent to fall into the diluent and then agitating the vial to ensure the lyophilised one or more active agents are fully reconstituted, thereby ensuring that there is no risk of contamination and that the solubilised one or more active agents can be rendered ready for use much faster than convention methods.
- the provision of a container storing both the lyophilised active agent and the diluent required to reconstitute the active agent results in less packaging being required to be manufactured and produces less waste when the container is to be disgarded.
- the steps of adding the diluent to the container and sealing the container with the closure may be carried out before or after the steps of adding a portion of the solution into the recess of the closure, lyophilising the solution in the recess of the closure and sealing the closure.
- the container may be a vial.
- the closure may be a vial cap.
- the closure is sterilised before the step of adding the solution to it.
- the interior of the container and the interior of the closure are sterile after the container is sealed to the closure.
- a sterilised closure ensures that the one or more active agents are not contaminated before the lyophilisation process and therefore that the lyophilised one or more active agents will be contaminant free. Ensuring that the interior of the container and the interior of the closure are sterile after the container is sealed to the closure allows the user to be confident that the diluent and the lyophilised one or more active agents are contaminant free and the resultant solubilised one or more active agents are safe to use, especially important in embodiments where the one or more active agents are a vaccine, for example.
- the one or more active agents may be a biologically active species, such as artificially expressed or reconstituted proteins, nucleic acid sequences or their mixtures.
- the one or more active agents may be medically active agents, such as a vaccine, for example.
- the diluent is typically an aqueous solution.
- the diluent may be saline solution, for example.
- the method of the present aspect of the invention may be used to store proteins expressed in a laboratory or to store the one or more active agents of a medicament for transportation from the manufacturer to the site where it will be administered, for example.
- the closure immediately preceding the step of lyophilising the solution in the closure, the closure is covered.
- the closure may be covered by the sealing element comprising a piston and the piston may define at least one aperture to allow the recess of the closure to be ventilated during the step of lyophilisation.
- the step of sealedly mounting the sealing element to the closure may seal the at least one aperture, thereby sealing the recess of the closure.
- the closure may be covered by a cover comprising a material that is permeable to the solvent of the active agent solution, such that during lyophilisation the solvent may sublime into the applied vacuum.
- the closure may comprise a frangible member.
- the solution lyophilised within the recess of the closure may be in contact with the frangible member such that the lyophilised one or more active agents is in contact with the frangible member.
- the piston of the sealing element may be moved from a first position to a second position so that in the second position the piston breaks and extends beyond the frangible member such that the lyophilised one or more active agents is combined with the diluent.
- the piston of the sealing element is manually operable between the first position and the second position.
- a pre-loaded container comprising a container body and a closure; the closure having a recess, a frangible member and a piston arranged adjacent to the frangible member; the container body retaining a diluent and the closure recess retaining one or more active agents lyophilised within the closure by the method of the first aspect of the invention; wherein the piston of the closure may be moved from a first position to a second position so that in the second position the piston breaks and extends beyond the frangible member such that the lyophilised one or more active agent is combined with the diluent.
- the piston may be part of a sealing element sealedly mounted to the closure.
- a pre-loaded container allows the one or more active agents that have been lyophilised within the cap of the vial and the diluent to be stored in the same sterile environment within which mixing and solubilisation of the one or more active agents will occur.
- the piston of the closure is manually operable between the first position and the second position.
- the portion of the piston forming an outer surface of the closure may comprise an air tight permeable or semi-permeable material such that a needle may penetrate the outer surface to extract the reconstituted active agent, but ensure that the lyophilised one or more active agents remain sterile and sealed within the closure.
- the piston may move from a first position to a second position such that the piston displaces a floor element of the frangible member of the closure, thereby allowing the lyophilised one or more active agents resting on the said floor element to fall into the diluent in the vial.
- the floor element may be pivotally mounted to the vial cap such that the movement of the piston results in the floor element being moved from a horizontal orientation to a vertical orientation and the lyophilised one or more active agents falls into the diluent.
- the lyophilised one or more active agents are compressed into a cake or tablet for efficient storage.
- the closure recess may retain a cake or tablet of lyophilised active agent such that when the piston is moved from the first position to the second position the cake or tablet of lyophilised active agent is combined with the diluent.
- the cake or tablet of lyophilised active agent may comprise a single active agent.
- the cake or tablet of lyophilised active agent may comprise more than one active agent.
- the cake or tablet of lyophilised active agent may comprise a different active agent to the active agent lyophilised within the closure.
- FIG. 1 is a side view of a pre-loaded vial (a) as stored and (b) after the one or more active agents have been applied to the diluent;
- FIG. 2 is a scheme of the method of manufacture of a pre-loaded vial.
- a pre-loaded vial 1 comprises a vial (acting as a container) 2 and a vial cap 4 (acting as a closure).
- the vial cap comprises a piston 6 , a base 8 (acting as a frangible member) and a recess 10 retaining a lyophilised vaccine 12 (acting as an active agent).
- the vial retains a diluent 14 (for example, saline solution) suitable for solubilising the lyophilised vaccine.
- the piston of the vial cap defines apertures, which are sealed after manufacture.
- the pre-loaded vial is manufactured by the following method, shown in FIG. 2 .
- the vial and vial cap are sterilised.
- a solution of the vaccine is prepared and one dose of the vaccine is placed into the recess of the vial cap.
- the recess of the vial cap is then covered by the piston.
- the apertures defined by the piston allow the recess of the vial cap to be ventilated.
- the vaccine solution within the vial cap is then lyophilised. That is, the vaccine solution is frozen and then warmed in vacuum to allow solvent in the vial cap to sublime into the vacuum through the apertures defined by the piston, leaving the vaccine protein behind in the vial cap.
- the advantage of lyophilisation is that the vaccine protein left behind in the vial cap is not structurally altered and is much more stable than the solubilised vaccine.
- the vial cap is then sealed such that the apertures of the piston are sealed and the recess of the vial cap is sealed to ensure that the lyophilised vaccine retained within the recess remains sterile.
- the diluent is added to the vial.
- the vial cap is then sealed to the vial such that the diluent within the vial is sealed from the outside and that the lyophilised vaccine is sealed from the diluent in the vial and the outside, thereby ensuring that the diluent and vaccine are retained in sterile conditions.
- a pre-loaded vial prepared by the above method may then be stored within a refrigerator or according to its recommended storage conditions to await use.
- the piston of the vial cap is pressed by the user (a) such that the piston moves through and extends beyond the base of the vial cap, thereby breaking the said base and allowing the lyophilised vaccine to fall into the diluent within the vial (b).
- the vial is then agitated to ensure that the vaccine is fully solubilised.
- the vaccine is then ready for use, and may be extracted by piercing the seal of the piston of the vial cap with a syringe and drawing the newly solubilised vaccine into the syringe after sterilisation of the outer surface of the vial cap.
- a lyophilised biologic may be stored in the pre-loaded vial using the method of the present invention for storage within a refrigerator or according to its recommended storage conditions.
- the piston may move from a first position to a second position such that the piston displaces the base of the vial, thereby allowing the lyophilised active agent resting on the said base to fall into the diluent in the vial.
- the base may be hinged such that the base is moved from a horizontal orientation to a vertical orientation such that the lyophilised active agent falls into the diluent.
Abstract
A pre-loaded container and a method of manufacturing a pre-loaded vial is provided wherein one or more active agents is lyophilised within the vial cap and the vial cap is then sealed onto a vial retaining a suitable diluent to form the pre-loaded vial. Lyophilising the one or more active agents within the vial cap ensures that the one or more active agents are retained in sterile conditions, that the lyophilised one or more active agents and the diluent may be stored efficiently, and that the one or more active agents may be solubilised in a sterile and efficient manner.
Description
- Methods of manufacturing sterile liquid containers and sterile liquid containers, more specifically methods of manufacturing vials and vials.
- In a number of scientific fields, such as medicine and biochemistry, for example, it is common to handle and use biological species in solution. Many of the biological species used are unstable and short lived in solution in vitro without the supporting infrastructure found in vivo, for example. Examples of such biological species include proteins, enzymes, nucleic acid sequences and vaccines. Many species that are unstable in solution have been found to be relatively stable if stored out of solution, that is, if the diluent used in their synthesis or extraction is removed.
- One way of doing this is lyophilisation, where the sample is frozen and then warmed in vacuum so that the solvent sublimes, leaving the species of interest intact. Therefore, for administration of a medicament where the one or more active agents is an unstable species in solution, for example, the one or more active agents and the diluent are often stored separately in two sterile storage units before administration.
- However, when the one or more active agents and the diluent are stored separately and combined immediately prior to administration, there is a risk of contamination of the medicament. To ensure that contamination does not occur, the combination of the one or more active agents and diluent is carried out using a lengthy and time consuming procedure.
- Accordingly, it is one object of the invention to provide a method of preparing active agents and an appropriate diluent for efficient and safe storage.
- In addition, the use of two containers and two sets of packaging is wasteful and harmful to the environment, creating twice the waste than that created for active agents stored in a single container.
- Accordingly, it is one object of the invention to provide a method of preparing active agents that produces less waste than conventional methods and is therefore more environmentally friendly.
- According to a first aspect of the invention there is provided a method of manufacturing a pre-loaded container for use in dispensing one or more active agents comprising the steps of;
- providing a container, a closure having a recess, and a solution containing one or more active agents;
- adding a portion of the solution into the recess of the closure;
- lyophilising the solution in the recess of the closure;
- sealing the closure; and
- adding a suitable diluent to the container and sealing the container with the closure.
- Preferably, the step of sealing the closure comprises sealedly mounting a sealing element comprising a piston.
- The piston may comprise a hollow column retained within a cylinder in the closure. The piston may comprise apertures suitable for ventilating the recess of the closure during the step of lyophilisation. The step of sealing the closure may seal the apertures of the piston. The piston may comprise a deformable feature extending from the outer surface of the closure such that deformation of the piston by the application of pressure to the said outer surface releases the lyophilised one or more active agents from the closure into the diluent of the container.
- Typically, in the prior art lyophilised active agent and diluent are stored in separate sterile containers. Therefore, for any one active agent to be available for use, two components must be sourced and stored. Generally, when the active agent is to be used, the diluent is extracted from its packaging using a syringe and the syringe is then inserted into the packaging of the active agent. The diluent is then added to solubilise the active agent. The active agent packaging must then be agitated to ensure that the active agent is fully dissolved to reconstitute the active agent into its solubilised form. Finally, the solution is then drawn into the syringe ready for use.
- The provision of container made according to the above method allows the active agent and diluent to be stored as a single entity, conserving space. In addition, the process of reconstituting the active agent is greatly reduced to a two step process of breaking the closure to allow the lyophilised active agent to fall into the diluent and then agitating the vial to ensure the lyophilised one or more active agents are fully reconstituted, thereby ensuring that there is no risk of contamination and that the solubilised one or more active agents can be rendered ready for use much faster than convention methods.
- Furthermore, the provision of a container storing both the lyophilised active agent and the diluent required to reconstitute the active agent results in less packaging being required to be manufactured and produces less waste when the container is to be disgarded.
- The steps of adding the diluent to the container and sealing the container with the closure may be carried out before or after the steps of adding a portion of the solution into the recess of the closure, lyophilising the solution in the recess of the closure and sealing the closure.
- The container may be a vial. The closure may be a vial cap.
- The closure is sterilised before the step of adding the solution to it.
- The interior of the container and the interior of the closure are sterile after the container is sealed to the closure.
- The provision of a sterilised closure ensures that the one or more active agents are not contaminated before the lyophilisation process and therefore that the lyophilised one or more active agents will be contaminant free. Ensuring that the interior of the container and the interior of the closure are sterile after the container is sealed to the closure allows the user to be confident that the diluent and the lyophilised one or more active agents are contaminant free and the resultant solubilised one or more active agents are safe to use, especially important in embodiments where the one or more active agents are a vaccine, for example.
- The one or more active agents may be a biologically active species, such as artificially expressed or reconstituted proteins, nucleic acid sequences or their mixtures. The one or more active agents may be medically active agents, such as a vaccine, for example.
- The diluent is typically an aqueous solution. The diluent may be saline solution, for example.
- Therefore, the method of the present aspect of the invention may be used to store proteins expressed in a laboratory or to store the one or more active agents of a medicament for transportation from the manufacturer to the site where it will be administered, for example.
- Preferably, immediately preceding the step of lyophilising the solution in the closure, the closure is covered. The closure may be covered by the sealing element comprising a piston and the piston may define at least one aperture to allow the recess of the closure to be ventilated during the step of lyophilisation. The step of sealedly mounting the sealing element to the closure may seal the at least one aperture, thereby sealing the recess of the closure. Alternatively, the closure may be covered by a cover comprising a material that is permeable to the solvent of the active agent solution, such that during lyophilisation the solvent may sublime into the applied vacuum.
- The closure may comprise a frangible member. The solution lyophilised within the recess of the closure may be in contact with the frangible member such that the lyophilised one or more active agents is in contact with the frangible member. The piston of the sealing element may be moved from a first position to a second position so that in the second position the piston breaks and extends beyond the frangible member such that the lyophilised one or more active agents is combined with the diluent.
- Preferably, the piston of the sealing element is manually operable between the first position and the second position.
- According to a second aspect of the invention there is provided a pre-loaded container comprising a container body and a closure; the closure having a recess, a frangible member and a piston arranged adjacent to the frangible member; the container body retaining a diluent and the closure recess retaining one or more active agents lyophilised within the closure by the method of the first aspect of the invention; wherein the piston of the closure may be moved from a first position to a second position so that in the second position the piston breaks and extends beyond the frangible member such that the lyophilised one or more active agent is combined with the diluent.
- The piston may be part of a sealing element sealedly mounted to the closure.
- The provision of a pre-loaded container according to the second aspect of the invention allows the one or more active agents that have been lyophilised within the cap of the vial and the diluent to be stored in the same sterile environment within which mixing and solubilisation of the one or more active agents will occur.
- Preferably, the piston of the closure is manually operable between the first position and the second position.
- The portion of the piston forming an outer surface of the closure may comprise an air tight permeable or semi-permeable material such that a needle may penetrate the outer surface to extract the reconstituted active agent, but ensure that the lyophilised one or more active agents remain sterile and sealed within the closure.
- The piston may move from a first position to a second position such that the piston displaces a floor element of the frangible member of the closure, thereby allowing the lyophilised one or more active agents resting on the said floor element to fall into the diluent in the vial. For example, the floor element may be pivotally mounted to the vial cap such that the movement of the piston results in the floor element being moved from a horizontal orientation to a vertical orientation and the lyophilised one or more active agents falls into the diluent.
- Often during the distribution of the lyophilised one or more active agents in methods of the art the lyophilised one or more active agents are compressed into a cake or tablet for efficient storage.
- The closure recess may retain a cake or tablet of lyophilised active agent such that when the piston is moved from the first position to the second position the cake or tablet of lyophilised active agent is combined with the diluent.
- The cake or tablet of lyophilised active agent may comprise a single active agent. The cake or tablet of lyophilised active agent may comprise more than one active agent.
- The cake or tablet of lyophilised active agent may comprise a different active agent to the active agent lyophilised within the closure.
- Optional features set out above in respect of the first and second aspects of the invention are optional features of either or both of the first and second aspects.
- An example embodiment of the present invention will now be illustrated with reference to the following Figures in which:
-
FIG. 1 is a side view of a pre-loaded vial (a) as stored and (b) after the one or more active agents have been applied to the diluent; and -
FIG. 2 is a scheme of the method of manufacture of a pre-loaded vial. - With reference to
FIG. 1 , apre-loaded vial 1 comprises a vial (acting as a container) 2 and a vial cap 4 (acting as a closure). The vial cap comprises apiston 6, a base 8 (acting as a frangible member) and arecess 10 retaining a lyophilised vaccine 12 (acting as an active agent). The vial retains a diluent 14 (for example, saline solution) suitable for solubilising the lyophilised vaccine. The piston of the vial cap defines apertures, which are sealed after manufacture. - The pre-loaded vial is manufactured by the following method, shown in
FIG. 2 . - The vial and vial cap are sterilised. A solution of the vaccine is prepared and one dose of the vaccine is placed into the recess of the vial cap. The recess of the vial cap is then covered by the piston. The apertures defined by the piston allow the recess of the vial cap to be ventilated. The vaccine solution within the vial cap is then lyophilised. That is, the vaccine solution is frozen and then warmed in vacuum to allow solvent in the vial cap to sublime into the vacuum through the apertures defined by the piston, leaving the vaccine protein behind in the vial cap. The advantage of lyophilisation is that the vaccine protein left behind in the vial cap is not structurally altered and is much more stable than the solubilised vaccine.
- The vial cap is then sealed such that the apertures of the piston are sealed and the recess of the vial cap is sealed to ensure that the lyophilised vaccine retained within the recess remains sterile.
- The diluent is added to the vial. The vial cap is then sealed to the vial such that the diluent within the vial is sealed from the outside and that the lyophilised vaccine is sealed from the diluent in the vial and the outside, thereby ensuring that the diluent and vaccine are retained in sterile conditions.
- A pre-loaded vial prepared by the above method may then be stored within a refrigerator or according to its recommended storage conditions to await use.
- With reference to
FIG. 1 , during use, the piston of the vial cap is pressed by the user (a) such that the piston moves through and extends beyond the base of the vial cap, thereby breaking the said base and allowing the lyophilised vaccine to fall into the diluent within the vial (b). The vial is then agitated to ensure that the vaccine is fully solubilised. The vaccine is then ready for use, and may be extracted by piercing the seal of the piston of the vial cap with a syringe and drawing the newly solubilised vaccine into the syringe after sterilisation of the outer surface of the vial cap. - In alternative embodiments, a lyophilised biologic may be stored in the pre-loaded vial using the method of the present invention for storage within a refrigerator or according to its recommended storage conditions.
- In further alternative embodiments, the piston may move from a first position to a second position such that the piston displaces the base of the vial, thereby allowing the lyophilised active agent resting on the said base to fall into the diluent in the vial. For example, the base may be hinged such that the base is moved from a horizontal orientation to a vertical orientation such that the lyophilised active agent falls into the diluent.
- Further modifications and variations may be made within the scope of the invention herein disclosed.
Claims (10)
1. A method of manufacturing a pre-loaded container for use in dispensing one or more active agents comprising the steps of;
providing a container, a closure having a recess, and a solution containing one or more active agents;
adding a portion of the solution into the recess of the closure;
covering the closure with a sealing element comprising a piston, the piston having at least one aperture to allow the recess of the closure to be ventilated during the step of lyophilisation;
lyophilising the solution in the recess of the closure;
sealing the closure by sealedly mounting the sealing element to the closure such that the at least one aperture of the piston is sealed, thereby sealing the recess of the closure; and
adding a suitable diluent to the container and sealing the container with the closure.
2. A method according to claim 1 , wherein the container is a vial and the closure is a vial cap.
3. A method according to any one preceding claim, wherein at least one of the one or more active agents is a biologic.
4. A method according to any one preceding claim, wherein at least one of the one or more active agents is a vaccine.
5. A method according to any one preceding claim, wherein the closure is sterilised before the solution is added to it.
6. A method according to any one preceding claim, wherein the interior of the container and the interior of the closure are sterile after the container is sealed to the closure.
7. A method according to any one preceding claim, wherein immediately preceding the step of lyophilising the solution in the closure, the closure is covered.
8. A pre-loaded container comprising a container body and a closure; the closure having a recess, a frangible member and a piston arranged adjacent to the frangible member; the container body retaining a diluent and the closure recess retaining one or more active agents lyophilised within the closure by the method of any one of claims 1 to 7 ; wherein the piston of the closure may be moved from a first position to a second position so that in the second position the piston breaks and extends beyond the frangible member such that the lyophilised one or more active agents is combined with the diluent.
9. A pre-loaded container according to claim 8 , wherein the piston of the closure is manually operable between the first position and the second position.
10. A pre-loaded container according to either one of claim 8 or 9 , wherein the closure recess retains a cake or tablet of lyophilised active agent such that when the piston is moved from the first position to the second position the cake or tablet of lyophilised active agent is combined with the diluent.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1114432.6 | 2011-08-22 | ||
GB201114432A GB2485254C (en) | 2011-08-22 | 2011-08-22 | A container having a recessed closure for drying and storing one or more active agents |
PCT/GB2011/052453 WO2013026995A1 (en) | 2011-08-22 | 2011-12-09 | Container and method of manufacture of container |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB2011/052453 A-371-Of-International WO2013026995A1 (en) | 2011-08-22 | 2011-12-09 | Container and method of manufacture of container |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/439,722 Continuation US20170224586A1 (en) | 2011-08-22 | 2017-02-22 | Container and method of manufacture of container |
Publications (1)
Publication Number | Publication Date |
---|---|
US20150107195A1 true US20150107195A1 (en) | 2015-04-23 |
Family
ID=44800654
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/119,280 Abandoned US20150107195A1 (en) | 2011-08-22 | 2011-12-09 | Container and Method of Manufacture of Container |
US15/439,722 Abandoned US20170224586A1 (en) | 2011-08-22 | 2017-02-22 | Container and method of manufacture of container |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/439,722 Abandoned US20170224586A1 (en) | 2011-08-22 | 2017-02-22 | Container and method of manufacture of container |
Country Status (3)
Country | Link |
---|---|
US (2) | US20150107195A1 (en) |
GB (1) | GB2485254C (en) |
WO (1) | WO2013026995A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020109194A1 (en) * | 2018-11-26 | 2020-06-04 | F. Hoffmann-La Roche Ag | Lyophilisate container and infusion kit |
WO2020109195A1 (en) * | 2018-11-26 | 2020-06-04 | F. Hoffmann-La Roche Ag | Manufacturing a flexible container |
CN111885990A (en) * | 2018-01-05 | 2020-11-03 | 太平洋有限公司 | Method and apparatus |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB201415869D0 (en) * | 2014-09-08 | 2014-10-22 | Eulysis Uk Ltd | Container And Closure |
JP7379158B2 (en) * | 2017-10-10 | 2023-11-14 | 大日本印刷株式会社 | Drug storage container, closing member, manufacturing method of drug storage container, microbial contaminant testing method, and solid preparation for buffer solution preparation |
Citations (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3603469A (en) * | 1968-04-11 | 1971-09-07 | Ambrogio Magni | Guarantee cap |
US3946732A (en) * | 1973-08-08 | 1976-03-30 | Ampoules, Inc. | Two-chamber mixing syringe |
US4601704A (en) * | 1983-10-27 | 1986-07-22 | Abbott Laboratories | Container mixing system with externally mounted drug container |
US4793475A (en) * | 1985-01-26 | 1988-12-27 | Celamerck Gmbh & Co. Kg | Closure caps for two-component packaging systems |
US5320603A (en) * | 1991-08-21 | 1994-06-14 | Arzneimitel Gmbh Apotheker Vetter & Co. | Hypodermic syringe for lyophilized medicament |
US5522155A (en) * | 1994-08-19 | 1996-06-04 | W. L. Gore & Associates, Inc. | Vented vial method of minimizing contamination of freeze-dried products |
US5533994A (en) * | 1988-12-27 | 1996-07-09 | Becton Dickinson France S.A. | Storage and transfer bottle designed for storing two components of a medicamental substance |
US5641010A (en) * | 1994-07-14 | 1997-06-24 | International Medication Systems, Limited | Mixing and dispensing apparatus |
US6786330B2 (en) * | 1997-10-14 | 2004-09-07 | Biogaia Ab | Two-compartment container |
US6840373B2 (en) * | 2002-05-16 | 2005-01-11 | Gregory A Gibler | Beverage storage and discharge cap assembly |
US6921087B2 (en) * | 2002-08-20 | 2005-07-26 | Nippon Tansan Gas Co., Ltd. | Sealing mechanism for vessel and cap to be used in the mechanism |
US20050211579A1 (en) * | 2004-03-29 | 2005-09-29 | Masayuki Makita And Bzi Co., Ltd. | Bottle cap |
US7325676B2 (en) * | 2003-07-11 | 2008-02-05 | Jose Luis Galaz Rodriguez | Container for containing two different separate products and mixing them |
US7473399B2 (en) * | 2003-05-22 | 2009-01-06 | Agilent Technologies, Inc. | Dispensing volumes of liquids using a flap septum |
US20090139951A1 (en) * | 2007-10-25 | 2009-06-04 | The Sunrider Corporation D.B.A. Sunrider International | Safety sealed reservoir cap |
US7748550B2 (en) * | 2004-11-23 | 2010-07-06 | Young Kook Cho | Sanitary double cap allowing addition of adjunct to contents of a container |
US8418865B2 (en) * | 2003-11-28 | 2013-04-16 | Young-Kook Cho | Bottle having two separated spaces in a bottle body |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3441179A (en) * | 1967-05-29 | 1969-04-29 | Ways & Means Inc | Mixing container |
US3578195A (en) * | 1969-01-16 | 1971-05-11 | Lyoflo Stopper Corp | Lyoflo-stopper |
US3802604A (en) * | 1972-02-28 | 1974-04-09 | Oreal | Device for storing two products separately and dispensing them simultaneously |
US3834571A (en) * | 1972-11-20 | 1974-09-10 | Warner Lambert Co | Container closure for lyophilized products |
US3881626A (en) * | 1972-11-20 | 1975-05-06 | Warner Lambert Co | Container closure for lyophilized products |
US4060911A (en) * | 1975-08-07 | 1977-12-06 | Behringwerke Aktiengesellschaft | Process for the preparation of a container closed under sterile conditions and containing lyophilized material |
US4084330A (en) * | 1976-07-02 | 1978-04-18 | Fts Systems, Inc. | Flask for freeze drying with adjustable seal |
US4089432A (en) * | 1977-05-06 | 1978-05-16 | The Upjohn Company | Vial and closure |
US4172457A (en) * | 1977-10-06 | 1979-10-30 | American Hospital Supply Corporation | Plural component mixing system and method |
US4550825A (en) * | 1983-07-27 | 1985-11-05 | The West Company | Multicompartment medicament container |
US4727985A (en) * | 1986-02-24 | 1988-03-01 | The Boc Group, Inc. | Mixing and dispensing apparatus |
US5303835A (en) * | 1992-06-24 | 1994-04-19 | Habley Medical Technology Corporation | Lyophilization cap and method |
US5447374A (en) * | 1994-01-03 | 1995-09-05 | Fts Systems, Inc. | Positioning device for temperature sensor in freeze drying |
US5958778A (en) * | 1995-09-22 | 1999-09-28 | The United States Of America As Represented By The Department Of Health And Human Services | Container for drying biological samples, method of making such container, and method of using same |
US5596814A (en) * | 1995-11-06 | 1997-01-28 | W. L. Gore & Associates, Inc. | Vented vial stopper for processing freeze-dried products |
JPH09278051A (en) * | 1996-04-09 | 1997-10-28 | Taisei Kako Kk | Crown-form lid having locking mechanism |
FI102642B1 (en) * | 1996-06-19 | 1999-01-15 | Orion Yhtymae Oyj | Reaction vessel or similar stopper |
US6199297B1 (en) * | 1999-02-01 | 2001-03-13 | Integrated Biosystems, Inc. | Lyophilization apparatus and methods |
EP1243245A4 (en) * | 1999-09-30 | 2006-10-18 | Astellas Pharma Inc | Infusion container and method of storing freeze-dried medicine |
CA2490358A1 (en) * | 2002-06-25 | 2003-12-31 | The Government Of The United States Of America, As Represented By The Se Cretary Of The Department Of Health And Human Services, Centers For Dise | Mixing vial |
US20050086830A1 (en) * | 2003-10-24 | 2005-04-28 | Zukor Kenneth S. | Processing cap assembly for isolating contents of a container |
PE20060672A1 (en) * | 2004-10-27 | 2006-08-28 | Glaxosmithkline Biolog Sa | PROCEDURE TO PREPARE A LYOPHILIZED MATERIAL |
DE102005038368A1 (en) * | 2005-08-13 | 2007-02-15 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Double chamber container for lyophilization, method for its filling and its use |
CN201436243U (en) * | 2007-12-20 | 2010-04-07 | 仙妮蕾德公司 | Storage room cover with safe seal |
FR2927316B1 (en) * | 2008-02-11 | 2010-05-14 | Biocorp Rech Et Dev | CLAMPING DEVICE HAVING A SUPPORT HAT AND CONTAINER EQUIPPED WITH SUCH A DEVICE |
JP2011530377A (en) * | 2008-08-11 | 2011-12-22 | アストラゼネカ・アクチエボラーグ | Filled insert for containers for mixing two or more components used in drug container systems |
FR2950035B1 (en) * | 2009-09-15 | 2011-09-02 | Raymond A & Cie | LOCKING COIFFE FOR CONTAINER WITH COLLAR |
FR2950865B1 (en) * | 2009-10-01 | 2011-10-28 | Raymond A & Cie | LOCKING CAP FOR A COLLARED CONTAINER WITH A FASTENING CAPSULE |
FR2967655B1 (en) * | 2010-11-24 | 2014-03-14 | Biocorp Rech Et Dev | DEVICE FOR CLOSING A CONTAINER, CONTAINER EQUIPPED WITH SUCH A DEVICE AND METHOD FOR CLOSING A BATCH OF SUCH CONTAINERS |
-
2011
- 2011-08-22 GB GB201114432A patent/GB2485254C/en active Active
- 2011-12-09 WO PCT/GB2011/052453 patent/WO2013026995A1/en active Application Filing
- 2011-12-09 US US14/119,280 patent/US20150107195A1/en not_active Abandoned
-
2017
- 2017-02-22 US US15/439,722 patent/US20170224586A1/en not_active Abandoned
Patent Citations (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3603469A (en) * | 1968-04-11 | 1971-09-07 | Ambrogio Magni | Guarantee cap |
US3946732A (en) * | 1973-08-08 | 1976-03-30 | Ampoules, Inc. | Two-chamber mixing syringe |
US4031892A (en) * | 1974-07-18 | 1977-06-28 | Ampoules Corporation | Two-chamber mixing syringe |
US4601704A (en) * | 1983-10-27 | 1986-07-22 | Abbott Laboratories | Container mixing system with externally mounted drug container |
US4793475A (en) * | 1985-01-26 | 1988-12-27 | Celamerck Gmbh & Co. Kg | Closure caps for two-component packaging systems |
US5533994A (en) * | 1988-12-27 | 1996-07-09 | Becton Dickinson France S.A. | Storage and transfer bottle designed for storing two components of a medicamental substance |
US5320603A (en) * | 1991-08-21 | 1994-06-14 | Arzneimitel Gmbh Apotheker Vetter & Co. | Hypodermic syringe for lyophilized medicament |
US5641010A (en) * | 1994-07-14 | 1997-06-24 | International Medication Systems, Limited | Mixing and dispensing apparatus |
US5522155A (en) * | 1994-08-19 | 1996-06-04 | W. L. Gore & Associates, Inc. | Vented vial method of minimizing contamination of freeze-dried products |
US6786330B2 (en) * | 1997-10-14 | 2004-09-07 | Biogaia Ab | Two-compartment container |
US6840373B2 (en) * | 2002-05-16 | 2005-01-11 | Gregory A Gibler | Beverage storage and discharge cap assembly |
US6921087B2 (en) * | 2002-08-20 | 2005-07-26 | Nippon Tansan Gas Co., Ltd. | Sealing mechanism for vessel and cap to be used in the mechanism |
US7473399B2 (en) * | 2003-05-22 | 2009-01-06 | Agilent Technologies, Inc. | Dispensing volumes of liquids using a flap septum |
US7325676B2 (en) * | 2003-07-11 | 2008-02-05 | Jose Luis Galaz Rodriguez | Container for containing two different separate products and mixing them |
US8418865B2 (en) * | 2003-11-28 | 2013-04-16 | Young-Kook Cho | Bottle having two separated spaces in a bottle body |
US20050211579A1 (en) * | 2004-03-29 | 2005-09-29 | Masayuki Makita And Bzi Co., Ltd. | Bottle cap |
US7748550B2 (en) * | 2004-11-23 | 2010-07-06 | Young Kook Cho | Sanitary double cap allowing addition of adjunct to contents of a container |
US20090139951A1 (en) * | 2007-10-25 | 2009-06-04 | The Sunrider Corporation D.B.A. Sunrider International | Safety sealed reservoir cap |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111885990A (en) * | 2018-01-05 | 2020-11-03 | 太平洋有限公司 | Method and apparatus |
WO2020109194A1 (en) * | 2018-11-26 | 2020-06-04 | F. Hoffmann-La Roche Ag | Lyophilisate container and infusion kit |
WO2020109195A1 (en) * | 2018-11-26 | 2020-06-04 | F. Hoffmann-La Roche Ag | Manufacturing a flexible container |
CN113164322A (en) * | 2018-11-26 | 2021-07-23 | 豪夫迈·罗氏有限公司 | Freeze-dried substance container and infusion set |
US11952155B2 (en) | 2018-11-26 | 2024-04-09 | Hoffmann-La Roche Inc. | Manufacturing a flexible container |
Also Published As
Publication number | Publication date |
---|---|
GB2485254B (en) | 2013-01-23 |
WO2013026995A1 (en) | 2013-02-28 |
GB2485254A (en) | 2012-05-09 |
US20170224586A1 (en) | 2017-08-10 |
GB2485254C (en) | 2013-12-25 |
GB201114432D0 (en) | 2011-10-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20170224586A1 (en) | Container and method of manufacture of container | |
US11246802B2 (en) | Container and closure | |
JP6223999B2 (en) | Method and apparatus for rapidly dissolving solid protein compositions | |
EP2812053B1 (en) | Device for accommodating a freeze-dried pharmaceutical product and method of manufacturing a sealed vessel accommodating a freeze-dried pharmaceutical product | |
RU2719937C1 (en) | Microneedles and methods for their production | |
JP4749328B2 (en) | Method for lyophilizing active factors | |
US20020104584A1 (en) | Reconstitution device and method of use | |
JP6985141B2 (en) | Container for mixing and dispensing fluid drug components | |
JPH11512014A (en) | Drug conversion device | |
JP2008526300A (en) | Airtight container delivery system | |
US20130035666A1 (en) | Stopper/Plunger for Carpules of Syringe-Carpule assembly | |
JP4536825B1 (en) | Manufacturing method of two-chamber type syringe for combined use and sleeve containing preparation | |
US20160158716A1 (en) | Novel reconstitution assembly | |
JP2018042997A (en) | Chamber for freeze-drying machine | |
ES2836828T3 (en) | Equipment to produce a vaccine | |
Zhuchenko et al. | Freeze-drying of biopreparations in dual-chamber syringes | |
CN201061615Y (en) | Ampule filled with injection | |
US20140257204A1 (en) | Apparatus for reconstituting and dispensing drugs for topical application |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |