US20220071844A1 - Filing system and methods for aseptic cartridge and dispenser arrangement - Google Patents

Abstract

A package for use with a beneficial agent delivery device. The package includes at least one filling chamber having a sealed penetrable access region, at least one compartment configured to hold a content, wherein the content includes at least one of a beneficial agent or a constituent of a beneficial agent, and at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment. At least a portion of the package is resealable to contain the content.

Description

TECHNICAL FIELD
• The present disclosure preferably, but without limitation, generally pertains to sealed packages, and more specifically pertains pre-fillable sterile packages and method of filling thereof.
BACKGROUND
• Medications, and in particular injectable medications, need to be stored sterile in aseptic commercial packages until the time of use. Some medications are stored in pre-filled single dose dispensing devices such as pre-filled syringes, for example, the pre-filled syringes from Vetter (Ravensburg, Germany). Yet most of injectable medication are stored in aseptic packages and are transferred to a dispensing device (i.e., drug delivery device) shortly before use. The term dispensing device include without limitation hypodermic syringes, micro needle syringes, micropumps, autoinjectors, jet injectors, topical dispensers, intradermal delivery devices, patch pumps, auricular dispensers, oral dispensers, eye droppers, autoinjectors, infusers, prefillable syringes, pre-filled syringes, cartridges for pen injectors, cartridges for auto-injectors, or any other type of drug delivery device.
• Several aseptic packages for storing injectable medications are commercially available. Perhaps the most common aseptic package for injectable products is glass vials. Some medications are stored in separate vials and are mixed just prior to use. Often this is done to improve the medication's stability or to extend the medication's shelf life. In one example, the medication is a vaccine that is kept dry in one vial to extend the vaccine thermo stability, and a companion vial stores a diluent that is dispensed to the vaccine vial via a syringe and needle prior to injection. In another example, the medication is a vaccine where one vial stores the formulated antigen and the second vial stores an adjuvant.
• Several existing products include a flexible package made from film or foils in which a product can be stored in an aseptic manner until the time of use. Some of these products further include a dispensing port communicating with the product in the dispensing package. In some cases, a rupturable barrier is presented between the port and the product to enhance the integrity of the package until the time of use. These flexible packages may comprise at least two product compartments that are mergeable prior to use to allow the substances from the different compartments to mix and form the dispensable product. In some cases, these packages are made from a film or a foil (together referred to as webs or web walls) where a first web wall is sealed to a second web wall to define the boundaries of a product compartment. These packages are sometimes referred to as bags, blisters, pouches or sachets.
• Packages for drugs, pharmaceutical agents or other beneficial agents are sometimes referred to as containers, primary containers, and container-closure systems. Packages are typically filled using a filling system. In the broader sense, fillings systems are configured to receive a package empty, fill the package, seal the package, and in some instances further arrange the package in a secondary package. At the filling step, the package is filled with one or more materials that are typically measured to receive a precise dose in the package. For liquids and other flowable substances, metering pumps are used to measure a precise dose into the package. Weighing the package is another common method of measuring a dose into a package. For powders, solids, and non-fluidic substances, filling systems may incorporate a volumetric transfer instrument or an acoustic measuring system to facilitate filling a precisely measured dose into a package.
• In most cases, the package is received at the filling system open, or it is open during the filling step such that the interior of the package is exposed to the surrounding environment. For pharmaceutical products, and particularly for sterile products that are administered parenteral such as by intravenous (IV) infusion and injection, rigorous measures are taken to prevent contamination, foreign biologic matter, and foreign particulates from entering into the container. In several cases, the pharmaceutical ingredient cannot be sterilized after filling, hence the filling process is executed using pre-sterilized packages in a controlled clean environment. Several types of filling systems incorporate the steps of receiving open packages, washing, drying, sterilizing, and inspecting the packages prior to filling. After filling, the packages are sealed, still in the controlled environment, by joining the walls of the package or by introducing a closure to the package.
• The filling process described above requires a sophisticated filling system that involves very high capital equipment expenditures and operation costs to the pharmaceutical filling company. These systems typically occupy significant and expensive clean-room space at the filling site while having a limited production throughput.
• Some of the foregoing shortfalls have been partially addressed by several packaging suppliers. The Stevanato Group, Nuovo Ompi division (Padua, Italy) provides pre-fillable containers that have been pre-washed, sterilized and inspected, in sterile nesting trays, hence avoiding some of the upstream steps of preparation steps prior to filling.
• Aseptic Technologies S.A. (Les Isnes, Belgium), and Medinstill (New Milford, Conn.) provide a pre-sterilized, sealed containers, particularly vials, and filling systems for accessing the container by piercing a rubber stopper with a piercing member, in a form of a needle, by which the package is filled; and resealing the access region after the package has been filled and the piercing member has been removed. Using such methods, these containers and filling systems avoid a number of upstream preparations typically required as filling steps at the filling site. Accessing the package for filling in a fluid-tight fashion, while the package is otherwise closed, reduces the risk of exposure of the interior of the package to contaminants, and can potentially reduce the controlled environment requirements during filling. The foregoing technologies have the potential of reducing capital equipment and filling operation complexities and costs while reducing contamination risks. However, such filling systems would benefit from further simplification and minimization of downstream operations after filling.
• One limitation that is common to the foregoing filling systems is the challenge to scale up production on a single line because of the filling metering systems. Whether the filled dose requires weighing or metering with a pump, manufacturing scale up require more measuring systems installed and operated on a single line, thereby resulting in more expensive, larger, and less reliable filling systems. Therefore, filling metering systems that allow manufacturing scale up without compromising reliability or increasing the system size and costs would be an important advance in this field.
• In some package applications, another limitation is the presence of air bubbles in the package after filling (i.e., sometimes referred to as headspace). Head space, and particularly inconsistency of head space, in a package may affect the accuracy of the dose received by a patient. This is particularly true with cartridges for pen injectors and auto injectors with limited options for removing air bubbles prior to injection, and where air may be injected to the patient in place of the actual drug. Another problem with headspace in the package is that some pharmaceutical products are sensitive to interaction with air, hence the presence of air bubbles may adversely affect the drug stability and efficacy.
• The packages and packaging limitation listed above are valid in other industries beside the pharmaceutical industry, including, for example, medical device packaging, food packaging, cosmetic packaging, and nutraceuticals packaging.
SUMMARY
• At least some aspects of the present disclosure overcome the disadvantages and limitations of the prior art by providing, for example, a low cost, simple and easy to fill package. Some aspects of the present disclosure provides an improved package and filling method thereof that simplify and minimizes the filling process avoiding several upstream and downstream steps to the filling step. Some aspects of the present disclosure provide a package and filling method thereof that eliminates headspace. Some aspects of the present disclosure eliminate and package or pre-filled delivery device assembly steps on the filling line. Another aspect of the present disclosure is to provide a package and a filling method thereof that allows economic scale up without compromising the filling system reliability.
• The terms dispenser, dispensing device, delivery device and delivering device are used interchangeably herein. The terms package, container, primary container, and container-closure system are used interchangeably herein. The term beneficial agent in pharmaceutical application may refer to a pharmaceutical product such as drug, a biologic drug, a substance of a drug, a vaccine, an adjuvant, a preservative, a diluent, a buffer and other materials that may need to be in the package for a specific application. Furthermore, in pharmaceutical applications the beneficial agent may be a material introduced to the package in the process of filling the package for filling or after filling including, a flushing material, a washing material, a chemical agent, a decontamination agent, a cleaning agent, a surfactant, a sterilization agent, hydrogen peroxide vapor, ethylene oxide, steam, sterile water, sterile air, nitrogen, solid object to enhance mechanical mixing during agitation, etc. The beneficial agent and its constituents may be in one or more formats including, a fluid, a liquid, a vapor, a solution, a suspension, a paste, a gel, a slurry, a frozen liquid, a gas, a solid, a powder, a lyophilized cake, granules, pellets, capsules, and tablets.
• The term filling refers to accessing the package to introduce material to the package. Filling further refers to introducing a beneficial agent to be sealed in the package and introducing a beneficial agent that is instantly removed from the package. Filling also refers to introducing or removing a beneficial agent after it has interacted with other materials in the package and after it has been contained in the package for a certain time. Filling refers to introducing a material to the package flowing through an accessing device or by releasing it from the surface or from within the accessing device.
• One aspect of the present disclosure relates to a package for use with a beneficial agent delivery device. The package includes at least one filling chamber having a sealed penetrable access region, at least one compartment configured to hold a content, wherein the content includes at least one of a beneficial agent or a constituent of a beneficial agent, and at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment. At least a portion of the package is resealable to contain the content.
• The package may include a delivery member operable to remove at least some of the content from the at least one compartment. The delivery member may be operable between a retracted position and a delivery position. The at least one filling chamber may include a plurality of filling chambers. At least one of the filling chambers may be configured for filling the at least one compartment. At least one of the filling chambers may be configured for removing content from the at least one compartment. The at least one compartment may include a plurality of compartments. The plurality of compartments may be separated by at least one frangible seal. The at least one channel may include a plurality of channels. At least one of the channels may be configured for filling the at least one compartment. At least one of the channels may be configured for removing content from the at least one compartment.
• The package may include a pre-formed port associated with each of the plurality of filling chambers. The package may include a fitment configured to deliver the content from the at least one compartment. The fitment may include one of a needle, a canula, a catheter, a tube, a connector, a Luer connector, a nozzle, a spray nozzle, a jet nozzle, a dispenser, an oral dispenser, a auricular dispenser, an ocular dispenser, a topical dispenser, or a coupler. The package may include at least first and second walls, the first wall at least partially defining the at least one filling chamber, the at least one channel, and the at least one compartment formed therein. At least a portion of one of the first and second walls may include a flexible material. At least a portion of one of the first and second walls may include one of a film and a foil material.
• The package may include a weakened portion to facilitate detaching the at least one chamber from the package. The package may include an insert positioned in one of the at least one chamber and the at least one channel. The insert may be configured to direct flow of the content into a predetermined area of the at least one compartment. The insert may be configured to facilitate sealing of the at least one channel. The package may include a sealing insert portion in the at least one chamber. The at least one channel may be configured to direct flow of the content onto a wall that defines a portion of the at least one compartment to minimize air mixing in the content during filling. At least one of the at least one channel, the at least one chamber, and the at least one compartment may be sealable.
• The package may include a resealable region, the resealable region being different from the access region. At least a portion of the package may be resealable. The portion of the package may be the at least one filling chamber. The portion of the package may be the at least one channel. The portion of the package may be the at least one compartment. The package may be supported by a backing. The backing may include a syringe. The package may include at least one pre-formed port formed in the backing and aligned with the at least one filling chamber. The package may be connectable to a delivery device. The package may include a cap removably positioned on the delivery device. The package may include a blow molded container. The package may include a molded container. The package may include a blister construction. The package may be formed as a single, unitary body.
• The plurality of channel may be arranged in fluid communication with one another. The plurality of chambers may be arranged in fluid communication with one another. The package may include a fitment, at least a portion of the fitment being positioned between the first and second layers. The package may include a fitment connected to an external surface of the package. The package may include a plurality of compartments and a plurality of channels, wherein the at least one filling chamber may be connected in flow communication with the plurality of compartments using the plurality of channels. The package may include a plurality of filling chambers and a plurality of channels, wherein the plurality of filing chambers are connected in flow communication with the at least one compartment using the plurality of channels. The package may include at least a portion of a heating element arranged in contact with a wall that defines at least a portion of the at least one compartment. The package may include a wall defining at least a portion of the at least one compartment, the wall comprising at least a portion of a heating element. The package may include at least a portion of a sensor configured to sense the presence of the content in the package. The package may include a seal configured to seal the access region, the seal being position externally to the at least one chamber. The seal may be configured to seal the access region, the seal being positioned internally of the at least one chamber. The at least one compartment may be connected in flow communication with a delivery device.
• The package may include a syringe. At least a portion of the at least one compartment may be defined between a plunger and a barrel of the syringe. The package may include a cartridge. At least a portion of the at least one compartment may be defined by one of a barrel and a plunger of the cartridge. The package may include an adapter comprising the at least one channel and the at least one chamber. The at least one channel may be movable to seal the at least one channel. The at least one channel may move linearly. The at least one channel may move rotationally. The syringe may include a plurality of plungers. The plungers may be movable during filling of the package with the content. The syringe may include a single plunger, the single plunger being may be immovable during filling of the package. At least one of the plungers may be immovable during filling of the package. At least one of the compartments may evacuate at one end and fills at an opposite end. The package may include a dual compartment syringe. At least one separate channel may be in fluid communication with each compartment of the syringe.
• The at least one channel may penetrate through a septum of the package into the at least one compartment. The at least one channel may penetrates through a wall of the package. The wall may include a rubber stopper. The rubber stopper may be a closure for the package. The at least a portion of the package may have a reduced structural integrity as compared to a structural integrity of a surrounding portion of the package so that the at least one chamber may be removable from the package. The at least one channel may be biased away from a wall of the at least one compartment. The at least one access region may include an openable barrier, the openable barrier comprising one of a a film, a foil, a rubber, and a molded part. The openable barrier may form a fluid tight seal around a device that pierces the access region.
• The at least one chamber may be configured to receive at least one of a flashing fluid, air, gas, dry gas, a decontamination fluid, benfeicial agent or a constituent thereof. The at least one chamber may be configured to remove from the package at least one of a flashing fluid, air, gas, dry gas, a decontamination fluid, benfeicial agent or a constituent thereof. At least a portion of at least one of the at least one channel and the at least one chamber may be collapsible to deliver content held therein into one of the at least one compartment and an external device. At least a portion of the at least one chamber may be collapsible to deliver content held therein into one of the at least one compartment and an external device.
• The package may be structurally joined to at least one other package. At least one compartment of at least a first package and at least one compartment of at least a second package share a at least one of the at least one channel and the at least one chamber. The package may include a delivery device connected to the package and operable to deliver the content from the package. The delivery device may include a syringe. The package may include a sealing insert positioned in at least one of the at least one channel and the at least one chamber, the sealing insert being configured to move from an opened position to a sealed position. The at least one channel may include a tubular structure with a pointed tip.
• Another aspect of the present disclosure relates to a package for use with a beneficial agent delivery device. The package includes at least one filling chamber, at least one compartment for receiving a content via the filling chamber, the content comprising at least one of a beneficial agent or a constituent of a beneficial agent, at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment, and a content sealed in the at least one compartment.
• The at least one compartment may include a first compartment holding a liquid content, and a second compartment holding anon-fluidic content. The at least one channel may be sealed. The at least one filling chamber may be resealable. The content may be a powder. The at least one filling chamber may include a plurality of filling chambers. The at least one channel may include a plurality of channels. The package may include a sealing insert positioned in at least one of the at least one channel and the at least one chamber, the sealing insert being configured to move from an opened position to a sealed position.
• Another aspect of the present disclosure relates to a device for delivery of a content. The device includes a package and a delivery device. The package includes at least one compartment configured to hold the content, wherein the content includes at least one of a beneficial agent and a constituent of a beneficial agent, at least one filling chamber having a sealed penetrable access region, and at least one channel connecting the at least one compartment in flow communication with the at least one filling chamber. The delivery device is connected to the package and operable to deliver the content from the package.
• The delivery device may include a syringe. The package may be configured to direct the content from the at least one filling chamber, through the at least one channel, and into the at least one compartment. The at least one compartment may include a plurality of compartments. The at least one filling chamber may include a plurality of filling chambers. The at least one channel may include a plurality of channels. The access region may provide fluid communication between the filling channel and an external system. At least one of the at least one filling channel, the at least one filling chamber, and the at least one compartment may be sealable. The access region may be configured to wipe a piercing member extending there through to limit foreign particles and contamination from reaching the at least one filling channel. The device may include a sealing insert positioned in at least one of the at least one channel and the at least one chamber, the sealing insert being configured to move from an opened position to a sealed position. One of the filling chambers may be used to evacuate the at least one compartment. One of the filling chambers may be used to fill the at least one compartment.
• Another aspect of the present disclosure relates to a filling adapter for use in filling a package that includes at least one compartment for storing a content, the content including at least one of a beneficial agent or a constituent thereof. The filling adapter includes an adapter body comprising at least one channel connectable to at least one compartment of the package, and at least one filling chamber in flow communication with the at least one channel, the at least one filling chamber having a sealed penetrable access region.
• The access region may be configured to be opened by a piercing member. The access region provides a fluid-tight seal with the piercing member. The barrier may include at least one of a foil, rubber, and molded plastic. At least one of the at least one channel, the at least one filling chamber, and the at least one compartment may be resealable. The adapter may include a resealing member configured to move from an opened position to a sealed position. The resealing member may be configured to heat seal one of the at least one channel and the at least one filling chamber. The adapter may be supported by a backing.
• The adapter may include a sealing insert positioned in at least one of the at least one channel and the at least one chamber, the sealing insert being configured to move from an opened position to a sealed position. The resealing member may be different from the access region. The adapter may be configured to fill the at least one compartment of the package with the content. The adapter may be configured to remove gas from the at least one compartment of the package. The filling adapter may be formed integrally with at least a portion of the package.
• Another aspect of the present disclosure relates to a filling system that includes at least one body for receiving a package, the package comprising at least one filling chamber, at least one channel, and at least one compartment, at least one piercing element operable to pierce the sealed package at an access region, and at least one sealing member operable to seal the package.
• The body may include a cavity for holding a package, comprising a region for at least one of at least one filling chamber, at least one channel, and at least one compartment. The piercing element may be configured to at least one of fill content into the package and remove content from the package. The piercing element pierces the package to access the at least one filling chamber. The cavity and the at least one compartment may be congruent. The filling system may have a controllable pressure therein configured to retain a wall of the package congurently in the cavity. The vacuum force may maintain at least a portion of a wall of the compartment congruent with the cavity. The filling system may provide a vacuum force that enhances a fluid-tight seal between the filling system and the access region.
• The sealing member may be operable to seal the at least one channel with a heat seal. The sealing member may be operable to seal by at least one one of heat sealing, pinching, linear actuation, and rotational actuation. The filling system may include a sensor operable to to sense a fluid in at least one the channel and chamber. The filling system may include a valve operable to stop filling of the at least one compartment. The filling system may include a washing device operable to wash the package. The at least one sealing member may be configured to seal the package while the access region may be being accessed. The filling system may include a plurality of piercing elements. The filling system may include a plurality of sealing members. The filling system may include at least one piercing element and the at least one sealing member are configured to pierce a plurality of access regions and perform plurality of seals in sequence. The sequence may include at least one of filling and removing at least one of air, a content, a beneficial agent, a decontamination agent, a disinfectant agent, a cleaning agent, a sterilization agent, a flushing fluid, a fluid, a liquid, a gas, a suspension, a gel, a paste, a powder, pellet, granules, a dry substance, a drying agent, vapor, moisture, and a constituent. The filling system may provide inspecting content removed from the package. The filling system may provide inspecting the content of the package by analyzing at least one of chemical composition, chemical concentrations, presence and concentration of particles, presence and concentration of particles larger than 50 microns, color, optical absorbance, optical reflectance, optical scattering, optical interference, pH, oxidation, conductivity, total organic carbons, and turbidity of the material. The filling system may include an instrument for substantially emptying the at least one filling chamber by one of collapsing the at least one filling chamber and removing conent with the piercing element. The at least one filling chamber may be sealed from the at least one compartment prior to emptying the at least one filling chamber. The at least one filling chamber may be sealed from the at least one compartment after emptying the at least one filling chamber.
• The filling system may include a fluidic system comprising at least one reservoir for at least one of receiving content from and delivering content to the package. The fluidic system may include the at least one piercing element. The at least one piercing element may be in fluid communication with the at least one reservoir via a tube. At least a portion of the fluidic system may be disposable. The filling system may include a preparation system for preparing the at least one piercing element and the access region for access by the at least one piercing element. The preparation system may include at least one of wipping, radiating, UV illumating, IR radiating, flushing, purging, puffing, and dispensing at least one of a cleaning agent, decontamination agent, sterilization agent, hydrogen-peroxide vapor, ethylene-oxide, sterile water, sterile air, water vapor, gas, and nitrogen gas to at least one of the at least one piercing element and the access region.
• Another aspect of the present disclosure relates to an adapter for a package. The adapter includes an interface to the package maintaining the sealed integrity of the package, at least one channel having a sealable portion, and at least one chamber comprising an openable access region, the access region being configured to open by insertion of a piercing member through the access region. The sealable portion is sealable while the access region is pierced by the piercing member.
• The access region may provide a fluid-tight seal with the piercing member. The access region may include at least one of a web portion, molded plastic, and rubber, pierceable by the piercing member. The adapter may include a resealing insert positioned in the at least one channel and the at least one chamber. The access region may be configured to receive a plurality of piercing members. At least a portion the adapter may be removable after sealing the sealing portion. The interface may be configured to be connected to one of a syringe, a cartridge, a vial, a plunger, a blister, a pouch, a bag, a sachet a cap, a syringe cap, and a needle cap, an infusion bag, a can, a canister, and a tube.
• The adapter may include a portion of one of a syringe, a cartridge, a vial, a plunger, a blister, a pouch, a bag, a sachet a cap, a syringe cap, and a needle cap, an infusion bag, a can, a canister, and a tube. At least a portion of the adapter may be integrated into one of a flexible package, a blister, a pouch, a film, a foil, a syringe, a cartride, a vial, a plunger, a blister, a pouch, a bag, a cap, a syringe cap, and a needle cap. At least a portion of the adapter may be formed in a blow-molded package. The adapter may be configured to be joined to a plunger of a delivery device. At least a portion of the at least one channel may be moveable from an open position to a sealed position. At least a portion of the at least one channel may be heat sealable.
• The adapter may be supported by a backing. The backing facilitates forming a seal with the piercing member that pierces the access region. The adapter may be arranged in flow communication with a plurality of compartments. The adapter may be arranged in flow communication with a plurality of packages. A portion of the adapter may be collapsible. At least a portion of the adapter may be movable from a storage configuration to a ready configuration wherein the chamber receives the piercing member. At least one wall of the package may be a flexible wall. The package may include one of a blister, a pouch, a sachet, a bag, a tube, a sleeve, a reservoir, a reservoir of a pump, a reservoir of an injector, a reservoir of an infusor, an infusion bag, and a blow-molded container.
• The present disclosure may also be directed to a syringe, a cartridge, a multi-chamber syringe, and a flexible package comprising the adapter disclosed herein.
• A further aspect of the present disclosure relates to a method of creating a sealed package containing a sterile content, the content comprising at least one of a beneficial agent or a constituent thereof. The method includes forming a package comprising at least one filling chamber, at least one compartment configured to hold the content, and at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment, and filling the package with the content while maintaining the at least one filling chamber, at least one compartment, and at least one channel immovable relative to each other.
• Another aspect of the present disclosure is directed to a method of creating a package containing a sterile content, the content comprising at least one of a beneficial agent or a constituent thereof. The method providing a sealed, sterile package comprising at least one filling chamber, at least one compartment configured to hold the content, and at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment, and filling the package with the content while maintaining a fixed volume for the package.
• The method may include providing a cavity sized to hold the package during filling, the cavity maintaining the fixed volume for the package. The package may be tilted relative to a horizontal plane during filling. The at least one filling chamber may include first and second filling chambers and the at least one channel may include first and second channels, the second filling chamber communicating with the at least one compartment via the second channel, and material may be removed from the package through the second channel during filling. The material may be a gas. During filling, the second channel may be oriented such that a connection of the second channel with the at least one compartment may be elevated relative to a connection of the first channel with the at least one compartment.
• Another aspect of the present disclosure relates to a method of sterile filling a pre-sealed package with a content, the content comprising at least one of a beneficial agent or a constituent thereof, wherein the package comprises at least one filling chamber, at least one compartment configured to hold the content, and at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment. The method includes opening the pre-sealed package at a penetrable access region to access the at least one filling chamber, filling the at least one compartment via the at least one filling chamber and at least one channel, and resealing the package.
• The method may include maintaining sterility of the package while opening, filling and resealing the package. The package may be opened by piercing the at least one chamber with a piercing member. The package may be resealed by sealing the at least one channel. The penetrable access region of the package may be pierced by a piercing member and may be filled through the piercing member. The method may include removing material from the package. Removing material from the package may occur during filling. The method may include inspecting the material that may be removed from the package. The method may include disqualifying the package based on the inspection.
• The at least one filling chamber may include first and second filling chambers, and the at least one channel may include first and second channels, and the material may be removed through the second chamber and the second channel. The method may include, prior to filling, at least one of introducing and removing at least one of a flushing fluid, a rinsing fluid, a decontamination fluid, a sterilization fluid, a chemical agent and a test reagent from the at least one compartment. The method may include resealing after the at least one of introducing and removing and prior to filling. The method may include filling through one of the at least one channel, and at least one of introducing and removing through another of the at least one channel. The method may include filling and at least one of introducing and removing through a common one of the at least one channels. The method may include piercing the at least one chamber with a piercing member, the method comprising at least one of filling and exhausting the at least one compartment and removing from the at least one compartment through the piercing member. The method may include inspecting the removed material.
• The at least one channel includes a first channel for filling the at least one compartment and a second channel for exhausting gas from the at least one compartment, the method further comprising tilting the package prior to filling the at least one compartment to orient the second channel vertically higher than the first channel. The method may include maintain a fixed volume of the package during filling. The method may include moving a wall of the container prior or during filling to define the container filled configuration. Moving the wall may include one of moving a plunger or holding a flexible wall in a cavity of the package. The method may include detaining a plunger in a filled position prior to or during filling. The method may include inspecting the package after resealing. The method may include drying the content after filling the at least one compartment. The at least one chamber may include a plurality of chambers, and drying occurs through separate of the plurality of chambers. The method may include joining the package to a backing prior to at least one of sterilizing the package and filling the at least one compartment. The method may include joining the package to a backing after at least one of sterilizing the package and filling the at least one compartment. The method may include removing a portion of the package after resealing. The method may include inspecting the package prior to opening.
• The method may include inspecting the package after resealing. The method may include providing a sensor and sensing a fill state of the at least one compartment with the sensor. The at least one channel includes a first channel configured to delivery the content to the at least one compartment, and a second channel configured to remove gas from the at least one compartment, the sensor sensing at least one property of a fluid in the second channel. Resealing may include one of displacing a portion of the at least one channel, heat sealing a portion of the package, and melting a fuse. Filling may include filling through a port formed in the backing. The method may include forming a fluid-tight seal between the piercing member and the package. The at least one compartment includes a plurality of compartments, and filling includes filling at least two of the plurality of compartments. At least one of filling and removing material may occur while the package may be joined to at least one other package. The method may include simultaneously at least one of filling and removing material from the package and the at least one other package. At least one of filling and removing material may occur through a common one of the at least one filling chamber or a common one of the at least one channel. The package may be resealed while the at least one filling chamber may be open. The method may include preparing at least one of the penetrable access region and the piercing member for aseptic filling. Preparing may include at least one of applying UV radiation, wiping, swabbing, or puffing at least one of a cleaning agent, a disinfectant, or a decontamination agent.
• The method may include wiping the piercing member while passing the piercing member through the penetrable access region into the at least one filling chamber, and wiping may remove foreign particulates from the piercing member. The at least one compartment may include at least first and second compartments, the method further comprising at least one of filling and removing for the second compartment by a different method than at least one of filling and removing for the first compartment. The method may include removing all air from the at least one compartment. The method may include substantially emptying the at least one filling chamber after resealing the package by at least one of removing material with the piercing member and collapsing the at least one filling chamber. The method may include substantially emptying the at least one filling chamber before resealing the package by collapsing the at least one filling chamber. The method may include providing the package sterile for filling.
• The package further may include a delivery device, and the method includes providing the package sterile to filling. The penetrable access region may include a web barrier, the method comprising forming a fluid-tight seal between the piercing member and the web barrier. The method may include moving the at least one channel from a first position to a second position to establish fluid communication between the at least one chamber and the at least one compartment. The at least one channel may be moved to provide access into the at least one compartment. The method may include drying the content in the at least one compartment by introducing a drying agent through the at least one channel and removing moisture through the at least one channel. The method may include controlling at least one of the pressure and temperature in the at least one compartment. The at least one channel includes a plurality of channels, the method further comprising sealing at least one of the plurality of channels. The method may include stopping the filling in response to signals from the sensor. Stopping the filling may include closing a valve.
• The method may include moving the at least one filling chamber from a storage position to a filling position to configure the at least one filling chamber to receive the piercing member. The method may include at least one of applying a vacuum and deforming a portion of the package to move the at least one filling chamber from the storage position to the filling position.
• Another aspect of the present disclosure relates to a method of forming a sealed package configured to hold a content, the content comprising at least one of a beneficial agent or a constituent thereof. The method includes forming a package having at least one filling chamber, at least one compartment configured to hold the content, and at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment, and concurrently sealing the package.
• The method may include forming at least one of the at least one filling chamber, the at least one compartment, and the at least one channel using a blow molding process. All of the compartments, channels and filling chambers may be integrally formed using a blow molding process. The method may include providing a web material defining first wall of the package, forming a cavity in the web material, integrally sealing the cavity to a second wall of the package to at least partially define at least one of the at least one channel, the at least one filling chamber, and the at least one compartment. All of the channels, chambers may be integrally formed between the sealed walls. The method may include providing a molded part defining a first wall of the package, the method comprising forming a cavity in the molded part, and sealing the cavity to a second wall of the package to at least partially define at least one of the at least one channel, the at least one filling chamber, and the at least one compartment. The method may include aseptically forming the sealed package from sterile components. The method may include sterilizing the pre-sealed package after forming. The method may include sterilizing the package by at least one of exposure to heat, radiation, gamma-radiation, e-beam irradiation, UV illumination, chemical agents, decontamination fluid, hydrogen peroxide vapor, or Ethylene Oxide, and flashing fluid.
• The package may include a semi-permeable region configured to allow chemical agents to penetrate into the at least one compartment. The semi-permeable region may be positioned in the at least one filling chamber. The method may include penetrating the at least one filling chamber and at least one of introducing chemical agent to the at least one compartment, introducing flashing fluid to the at least one compartment, and removing material from the at least one compartment. The method may include resealing the package. The method may include removing material from the package and inspecting the removed material, wherein the inspection includes analyzing at least one of chemical composition, chemical concentrations, presence and concentration of particles, presence and concentration of particles larger than 50 microns, color, optical absorbance, optical reflectance, optical scattering, optical interference, pH, oxidation, conductivity, total organic carbons, and turbidity of the material.
• The method may include penetrating an access region of the at least one chamber with a piercing member in a fluid-tight fashion, the piercing member being configured to perform at least one of introducing chemical agent, introducing flashing fluid, and removing material from the compartment. The method may include introducing at least two materials to the container. The at least two materials are introduced simultaneously. The at least two materials are introduced to the at least one compartment through a common one of the at least one channel and a common one of the at least one filling chamber. The at least one channel includes at least two channels, and the at least one filling chamber includes at least two filling chambers, and the at least two materials are removed from or introduced to the at least one compartment via the at least two channels and the at least two filling chambers. The method may include introducing material to and removing material from the at least one compartment occurs simultaneously.
• The method may include removing at least a portion of the at least one filling chamber of the package after sealing the package. The at least one compartment includes at least first and second compartments, the method comprising introducing material to or removing material from the first and second compartments via the at least one filling chamber. The method may include inspecting the content of the package. The method may include inspecting material removed from the at least one compartment. Inspecting may include analyzing at least one of chemical composition, chemical concentrations, presence and concentration of particles, presence and concentration of particles larger than 50 microns, color, optical absorbance, optical reflectance, optical scattering, optical interference, pH, oxidation, conductivity, total organic carbons, and turbidity of the content.
• The at least one filling chamber may include a penetrable access region, and the method may include penetrating the access region with a piercing member. The method may include forming a fluid-tight connection between the piercing member and the access region. The piercing device may be configured to perform at least one of introducing material to and removing material from the at least one compartment. Inspecting may include non-contact inspecting of the content of the package. The method may include moving the material in the package during inspecting. The method may include moving the material in the package by at least one of agitation, gravity, acceleration, electric field, magnetic field, pressure, and acoustic wave manipulation. The method may include at least one of attributing, disqualifying, rejecting, or approving the package based on the inspecting.
• The method may include forming a plurality of packages that are joined to one another. The plurality of packages may include at least one of a joined channel and a joined chamber. The plurality of packages include first and second packages, wherein at least one of the joined channel and the joined filling chamber may be connected in fluid communication with the at least one compartment of the first package and the at least one compartment of the second package. The method may include at least one of introducing and removing material from at least the first and the second compartments through at least one of the joined chamber and the joined channel. The packages may be resealed. The method may include joining the package to at least one of a backing and a delivery device. The backing may be pre-sterilized and may be aseptically joined with the package. The package may be sterilized after the step of joining the backing. The method may include establishing fluid communication with the package through at least one access port formed in the backing. The fluid communication may be established by at least one piercing member accessing the package through the access port. The at least one piercing member establishes fluid-tight communication with at least one of the package and the backing.
• The method may include joining the package to a delivery device. The delivery device may be pre-sterilized and may be aseptically joined with the package. The package may be sterilized after the step of joining the delivery device. The delivery device may be a syringe and the package may be joined at a dispensing end of the syringe. The method may include disposing an insert in the package prior to sealing. The at least one insert may be disposed in at least one of the at least one channel and the at least one chamber. The at least one insert may include at least one of a seal, a flow deflector, a flow director, a fuse, a fitment, and a plug. The method may include creating an opening in the package and positioning the insert such that at least a portion of the insert may be exposed externally from the package. The method may include separating the insert from the compartment by a frangible seal.
• A further aspect of the present disclosure relates to a method of creating a sealed package, the packing comprising a compartment containing a sterile content, the content comprising at least one of a beneficial agent or a constituent thereof, and a portion of the compartment being moveable from a first configuration to a second configuration to change a volume of the package and to remove at least a portion of the content after opening the package. The method includes forming the sealed package and maintaining the package in substantially the first configuration while filling the package with the content.
• The package may include a penetrable access region and a resealing region, the access region being different than the sealing region, and the method includes filling the package via the access region. The method may include opening the access region, filling the package through the access region, and sealing the resealing region. The method may include removing material from the package during filling. Sealing the resealing region may occur while the access region is open. The package may include a barrel and plunger arrangement at least partially defining the compartment, and the method further includes maintaining the plunger in a fixed position relative to the barrel to provide the filled configuration before, during, and after filling. The package may include at least one filling chamber and at least one channel providing flow communication between the at least one filling chamber and the compartment, and the method further includes accessing the package by piercing the at least one chamber, and resealing the package by sealing the at least one channel.
• The at least one filling chamber may include first and second filling chambers, and the at least one channel may include first and second channels, the second channel providing flow communication between the second chamber and the compartment, the method further comprising accessing the second chamber. The method may include maintaining the package in the first configuration during filling of the compartment. The package may include a flexible wall, the flexible wall being a portion of the compartment, the method further comprising maintaining the flexible wall in a cavity to define the first configuration of the package. The flexible wall may be maintained in the cavity by applying vacuum to the external surface of the package. The flexible wall may be maintained in the cavity by applying pressure in the package. The flexible wall congruently maintains the cavity shape by one of applying vacuum to the external side of the flexible wall and applying pressure to the inner side of the flexible wall.
• The package may include a plurality of compartments, and filling the package includes filling the plurality of compartments with the content. The method may include filling the plurality of compartments simultaneously. The method may include filling and resealing the plurality of compartments consecutively. The method may include tilting the package during filling to remove gas from the compartment. The method may include providing at least one sensor, and sensing when the compartment may be full of the content. The package may include at least one filling chamber and at least one channel providing flow communication between the compartment and the at least one filling chamber, wherein the sensor senses the content may be being removed in at least one of the at least one filling chamber and the at least one channel.
• The method may include providing a plurality of package layers, and forming the sealed package may include forming the compartment between the plurality of layers. The method may include sealing the plurality of layers together to enclose the compartment. The method may include forming at least one of at least one channel and at least one filling chamber between the plurality of layers, the at least one channel providing flow communication between the at least one filling chamber and the compartment. The method may include maintaining the package in substantially the first configuration while filling the package with the content includes fixing the first configuration during filling.
• Another aspect of the present disclosure relates to a method of creating a sealed package containing a sterile content, wherein the content includes at least one of a beneficial agent or a constituent thereof. The method includes forming a package comprising at least one filling chamber, at least one compartment configured to hold the content, and at least one channel connecting the at least one filling chamber in fluid communication with the at least one compartment, and filling the package with the content while maintaining the at least one filling chamber, at least one compartment, and at least one channel immovable relative to each other.
• A further aspect of the disclosure relates to a method for filling a sealed package, the package comprising at least one compartment, at least one access region, and at least one dispensing portion for removing at least a portion of the content. The method includes providing the package sealed, maintaining the at least one compartment and all the dispensing portions uninterruptedly sealed, filling the at least one compartment through the at least one access region, and resealing the package.
• The access region may be accessed for filling in a fluid-tight fashion. The package may include a barrel, and a plunger disposed in the barrel to at least partially define a sealed compartment between the barrel and plunger, and wherein the plunger may be moveable between a dispensed position and a filled position, the method may include moving the plunger from a dispensed position to a filled position during filling. The method may include removing material from the package through an access port. The material may be at least one air bubble. The package may be one of a blister, a pouch, a sachet, a can, a bottle, a vial, a syringe, a cartridge, a blown-container, and a molded container. The package may be resealed at a different region than the access region.
• The package may be resealed while the access region may be open. The package may include first and second walls sealable there between by a frangible seal portion and a permanent seal portion, the permanent seal portion having a peeling force greater than a peeling force of the frangible seal portion, and the method may further includes joining the first wall and the second wall along a closed contour defining therein at least one compartment and at least one access region, which are in fluid communication, and sealing between the at least one access region and at least one compartment by a permanent seal.
• The method may include creating a frangible seal between the compartment and the at least one dispending portion. The method may include creating a permanent seal around the at least one compartment and the at least one dispensing portion. The permanent seal may circumscribe the at least one compartment and the at least one dispensing portion.
• Another aspect of the present disclosure relates to a method for accessing a sealed package, the package comprising at least one compartment and at least one access region for at least one of filling and removing material from the at least one compartment, and the method including providing the package sealed, accessing the package to form a fluid-tight communication with the at least one compartment, and resealing the sealed package at a region different than the at least one access region.
• The package may be resealed while the at least one access region may be open. The package may be accessed to remove a sample. The package may be accessed by a piercing member. The material may be at least one of filled and removed from the package by flowing through the piercing member. The material may be at least one of filled and removed from the package by detaching from or attaching to the piercing member, respectively. The package may include a seal between the at least one access region and the at least one compartment, the seal being openable to establish fluid communication between the at least one compartment and the at least one access region, and the method further includes opening the openable seal, transferring content from the package to the at least one access region, resealing the openable seal, and accessing the at least one access region. The method may include removing the at least one access region. The method may include at least one of removing material from and introducing material to the at least one access region when accessed.
• The applications of the present invention are not limited to drug delivery, which is provided herein by way of example. The teachings described herein can be applied to packages and dispensing devices in other areas such as, for example, glue dispensing, chemicals dispensing, etc., and medical device packaging, food packaging, electronics packaging, chemical packaging, biologic packaging, cosmetic and nutraceuticals packaging, etc. The present disclosure provides various configurations for accomplishing this.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIGS. 1aand 1bare top and bottom perspective views of an example package in accordance with the present disclosure.
• FIG. 1cis an exploded perspective view of the package shown inFIG. 1b.
• FIG. 1dis a close-up view of a filling chamber and filling channel of the package ofFIG. 1a.
• FIG. 1eis a close-up view of the filling chamber and filling channel ofFIG. 1dwith the filling channel sealed closed.
• FIG. 1fis a perspective view of the package ofFIG. 1atrimmed to remove the filling chambers.
• FIG. 1gis a perspective view of an alternative version of the package ofFIG. 1A with a fitment removed.
• FIGS. 2a-2cshow steps of sealing the package shown inFIG. 1a.
• FIGS. 3a-3fshow another example package in accordance with the present disclosure being filled with a filling device.
• FIG. 4 is a close-up view of the package and filling device ofFIG. 3bwith an insert positioned therein.
• FIGS. 5a-5dshow an example delivery assembly including a package and a delivery device in accordance with the present disclosure.
• FIGS. 6aand 6bare perspective views of another example package in accordance with the present disclosure.
• FIG. 6cis an end view of the package ofFIGS. 6aand6b.
• FIGS. 6dand 6eare cross-sectional views of the package ofFIG. 6abeing filled with a filling device.
• FIGS. 7a-7cshow alternative package embodiments being filled by various filling devices in accordance with the present disclosure.
• FIGS. 8a-8fshow another example package in accordance with the present disclosure.
• FIGS. 9 and 10 show alternative embodiments of the package shown inFIGS. 8a-8e.
• FIG. 11 is a perspective view of a plurality of the packages ofFIGS. 8a-8fconnected together as a web.
• FIGS. 12aand 12bshow alternative embodiments of the web shown inFIG. 11.
• FIGS. 13a-13fare flow diagrams showing various methods of forming the packages disclosed herein.
• FIGS. 14a-14fshow another example package in the form of a cartridge in accordance with the present disclosure.
• FIGS. 15a-15eshown another example package in the form of a cartridge in accordance with the present disclosure.
• FIGS. 16a-16fshow another example package in the form of a cartridge in accordance with the present disclosure.
• FIG. 17ashows another example package formed using a blow-mold- fill method in accordance with the present disclosure.
• FIG. 17bis a cross-sectional view of the package shown inFIG. 17a.
• FIGS. 18aand 18care perspective views showing another example package having a syringe construction in accordance with the present disclosure.
• FIG. 18bis a cross-sectional view of the package ofFIG. 18a.
• FIG. 18dis a cross-sectional view of an alternative version of the package ofFIGS. 18a-18c.
• FIGS. 19a-19eshow cross-sectional views of an alternative embodiment of the package shown inFIGS. 18a-18bhaving a plurality of plungers in accordance with the present disclosure.
• FIG. 20ais a perspective view of another example package in the form of a syringe in accordance with the present disclosure.
• FIGS. 20b-20dare cross-sectional views of the package ofFIG. 20a.
• FIG. 21ais a perspective view of another example package in the form of a syringe in accordance with the present disclosure.
• FIG. 21bis a cross-sectional view of the package ofFIG. 21a.
• FIGS. 21cand 21dare perspective views of the package ofFIG. 21awith the adapter removed.
• FIGS. 22a-22dshow cross-sectional views of an example package in the form of a vial in accordance with the present disclosure.
• FIGS. 23aand 23bshow another example package in the form of a vial in accordance with the present disclosure.
• FIGS. 24a-24cshow another example package having a heating element in accordance with the present disclosure.
• FIGS. 25a-25eare perspective views of an example package in the form of a syringe in accordance with the present disclosure.
• FIG. 26 is a side view of the package ofFIGS. 25a-25e.
• FIG. 27 is a cross-sectional view of the package ofFIG. 26 and a filling station of an example filling system in accordance with the present disclosure.
• FIGS. 28aand 28bare cross-sectional views of an example filling head for use with the filling station ofFIG. 27 for filling the package ofFIG. 26.
• FIGS. 29aand 29bare cross-sectional views of another example filling head for use in filling the package ofFIGS. 25a-26b.
• FIGS. 30a-30eshow filling of the package ofFIGS. 25a-25eusing the filling station ofFIG. 27 and the filling head ofFIGS. 28aand28b.
• FIGS. 31aand 31bare a perspective views of another example package in the form of an infusion bag in accordance with the present disclosure.
• FIG. 31cshows a filling chamber of the package ofFIGS. 31aand 31bcollapsed prior to filling of the package.
• FIGS. 32aand 32bare perspective views of another example package in the form of an infusion bag having an access insert in accordance with the present disclosure.
• FIGS. 33aand 33bare perspective view of another example package in the form of an infusion bag having an actuatable access member in accordance with the present disclosure.
• FIGS. 34a-34dshow another example actuatable access member for use in the infusion bag ofFIGS. 33aand33b.
DETAILED DESCRIPTION
• FIGS. 1a-1bshow anexample package10 in accordance with the present disclosure. Thepackage10 includes first andsecond compartments20a,20b,first andsecond filling chambers22a,22b,first andsecond filling channels24a,22b,and first and second layers orwalls26,28. Thepackage10 may also include at least first and secondfrangible seal portions30,32, first andsecond access regions34a,34b,and afitment36.
• FIG. 1cshows thefirst layer26 as a pre-formed flexible wall of thepackage10. Thefirst layer26 includes first and second compartment cavities40a,40b,which when later sealed using thesecond layer28 form the first andsecond compartments20a,40b.Thefirst compartment20areceives a first constituent (e.g., a beneficial agent or constituent of a beneficial agent). Thesecond compartment20breceives a second constituent (e.g., a beneficial agent or constituent of a beneficial agent) which is typically different from the first constituent. Thefirst layer26 also includes an uninterrupted area at a peripheral edge of the first compartment cavity40a,which is spaced between the first and second compartment cavities40a,40b,that subsequently becomes the firstfrangible seal portion30. A second uninterrupted area at the peripheral edge of the second compartment cavity40b,which is spaced between the first compartment cavity40band afitment cavity46, subsequently defines the secondfrangible seal portion32.
• The first andsecond layers26,28 may have flexible characteristics and may be referenced as flexible walls of thepackage10. A flexible wall may include a portion of the package that is deformable by pressure of force to substantially affect a configuration of the package and accuracy of a volume of at least one of the first andsecond compartment20a,20b.
• Typically, thefirst compartment20adefined by the first compartment cavity40areceives a liquid. Thesecond compartment20bdefined by the second compartment cavity40btypically receives a non-fluidic material or a poorly flowing material such as, for example, powder, compressed or agglomerated powder, granules, pellets, solid, tablets, capsules, slurries, paste, hibiscus fluid, emulsions, or a combination thereof. The substance received in thesecond compartment20bis filled into thesecond compartment20bby an appropriate filling system that provides the type of material that needs to be filled. Thesecond compartment20bmay also be filled with water or other viscosity fluid. In some examples, it may be challenging to completely fill thesecond compartment20bwith water or aqueous solution due to surface tension and other properties of the fluid, which may make it challenging to maintain the fluid in the compartment as the compartment is being sealed.
• Another challenge related to filling thepackage10 is that liquid filling is a relatively slow manufacturing process for a number of factors, one of which is avoiding foaming or bubble formation as the liquid is filling at least one of the first andsecond compartments20a,20b.
• The substance used to fill thesecond compartment20bmay be a loose powder or another form of disbursable dry substance, which may be challenging for filling asecond compartment20b.
• Thefirst compartment20atypically provides another arrangement for efficiently filling a low viscosity fluid to substantially fill thefirst compartment20a.In one example, thepackage10 includes the first andsecond filling chambers22a,22bprovided in flow communication with thefirst compartment20avia the first andsecond filling channels24a,24b,respectively. Portions of the first andsecond filling chambers22a,22bmay be pre-formed in afirst layer26 as first and second chamber cavities42a,42b.Portions of the first andsecond filling channels24a,24bmay be pre-formed in thefirst layer26 as first and second channel cavities44a,44b.The term pre-formed in the context of this figure may be at least one of thermoforming, vacuum forming, cold forming, plug assign forming and pressure forming, however similar package configurations may be made from materials and processes other than web material and processing thereof. Hence in some embodiments at least a portion of at least one of the cavities40a,40b,42a,42b,44a,44b,may by pre-formed using injection molding, blow molding, injection blow molding, stamping, machining, deposition and etching. Thefirst filling chamber22amay be referred to as an inlet filling chamber. Thesecond filling chamber22bmay be referred to as an outlet, exhaust, or evacuation filling chamber.
• The first filling channel24amay be referred to as an inlet channel or passageway, or a first pre-formed filling channel. Thesecond filling channel24bmay be referred to as an outlet passageway, or a channel, or a second pre-formed filling channel. The first andsecond filling channels24a,24bmay be collectively referred to as Tillable channels, filling channels, or passageways used to fill the first andsecond compartments20a,20b.
• The first andsecond layers26,28 may be portions of a web that have features of thepackage10 formed therein. It may be understood by those of skill in the art that in a normal manufacturing process an array of details for multiple cartridges may be formed in a large spread of thefirst layer26 and may be handled simultaneously at subsequent forming and filling steps. Thepackage10, or any portion thereof (e.g., the first orsecond layers26,28) may comprise a blister package construction that defines pre-formed cavities such as the first and second compartment cavities40a,40b.Thefirst layer26 may be pre-formed from a flat web by one or more of the processes including, for example, thermo forming, cold forming, vacuum forming, pressure forming, plug assist forming, or pre-forming from non-web raw material such as by injection molding, blow molding, injection-blow molding, blow-fill-seal, blow-fill-insert-seal, or other methods known in the art. In some embodiments at least one of thefirst compartment20a,a channel,24a,24b,and achamber22a,22bis not performed without affecting the generality of this disclosure.
• FIG. 1dis a close-up view of the first fillingchamber22aand first filling channel24ashown inFIG. 1aprior to sealing thepackage10.FIG. 1eis a close-up view of thepackage10 after being sealed along the first filling channel24a.Thesecond filling channel24bis typically also sealed. Thepackage10 may be sealed at other locations such as, for example, at the first andsecond filling chambers22a,22b,at the first compartment40 (e.g., adjacent to an inlet of the first andsecond filling channels24a,24b), or at a location overlapping any combination of the filling chambers, filling channels, and first compartment. Sealing the package may comprise deforming (or pinching) at least one portion of the package to bring thefirst wall26 and second wall of thepackage28 into contact than applying heat to cause the walls to join is a sealed fashion.
• FIG. 1fis a bottom perspective view of thepackage10 after a portion of the package has been removed.FIG. 1fshows a subsequent step of the manufacturing process of thepackage10. After the first andsecond compartments20a,20bhave been filled, the first andsecond layers26,28 are hermetically sealed to provide a permanent seal region38 around a periphery of thepackage10 as shown inFIGS. 2a-2cand first and secondfrangible seal portions30,32 positioned between the first andsecond compartments20a,20band between thesecond compartment20band thefitment36, respectively (seeFIGS. 2a-2c). In one arrangement, an adhesive is used to secure the first andsecond layers26,28 together to provide a controllable peeling (adhesion) force where a lower sealing temperature (for example, about 300° F.) results in a peelable adhesion (“frangible seal”) and a higher sealing temperature (for example, about 420° F.) results in a permanent, non-peelable adhesion. In one arrangement, the frangible seal peeling force is about 1000 g/in², and the permanent seal is greater than about 1600 g/in².
• In one example, the first sealing step provides adhering substantially all of the uninterrupted surface of thefirst layer26 to the second layer28 (e.g., extending around substantially an entire circumference of the first andsecond compartments20a,20bwith the exception of the first andsecond filling chambers22a,22band the first and secondfrangible seal portions30,32). The first andsecond filling channels24a,24bremain open and unsealed to permit fluid communication between the first andsecond compartments20a,20band the first andsecond filling chambers22a,22b.With the first andsecond layers26,28 now attached to each other, flow communication is provided between thefirst compartment20aand the first andsecond filling chambers22a,22bvia the first andsecond filling channels24a,24b,which are formed between the first andsecond layers26,28. Access regions are defined in thesecond wall28 in front of the first andsecond chambers22aand22b
• Thesecond layer28 may include first andsecond access regions34a,34bin the access regions, as shown inFIGS. 1band2b.The first andsecond access regions34a,34bmay be formed concurrently with accessing the first andsecond filling chambers22a,22bduring filling. The first andsecond access regions34a,34bmay be formed using any one of the means known in the art such as, for example, punching, die cutting, and laser cutting, and piercing with a piercing member or a filling member. In one example, the second layer22 is pierced by a filling device during a filling step when filling thefirst compartment20a.In another arrangement, thefirst compartment20ais filled with a first substance through thefirst access region34awhile thesecond access region34ballows for evacuation of gases from thefirst compartment20aduring filling. A filling source may be associated with at least one of the first andsecond access regions34a,34bduring the filling process to facilitate the introduction of a substance to thefirst compartment20a,and drawing the gases through thesecond filling chamber22b.At least one of the first andsecond access regions34a,34band second fillingchannel24bmay be sized to prevent the substance from reaching thesecond access region34b.In one arrangement the filling device includes a needle or a tube that is formed to reach into the first filling channel24a.The gases drawn through the first or second fillingchamber22a,22bor the first andsecond filling channels24a,24bmay be connected to an exhaust line (not shown) that draws the gases away from thepackage10. One of the first andsecond filling chambers22a,22bthrough which gas is evacuated may be referred to as a gas evacuation chamber. The gas evacuation characteristics achieved by the present designs are not known to exist in the prior art because prior art designs are typically not filling a pre-sealed package that maintains an aseptic environment prior to, during and after filling. The challenges associated with removing gas from an unsealed package are different, and in many scenarios less complicated than gas evacuation from a pre-sealed package in which an aseptic environment is maintained.
• In at least one example, the filling device (e.g.,device102 shown inFIGS. 3a-3f) may include a cylindrical filling tube with a diameter greater than that of the first orsecond access region34a,34bwithin which the tube is inserted. An interface between the filling device (e.g., acylindrical filling tube104 shown inFIGS. 3a-3f) and thepackage10 may provide a tight fit with a fluid-tight seal when introduced through one of the first andsecond access regions34a,34b.In one arrangement, the first andsecond access regions34a,34bare formed during the filling step by a sharp object such as a hollow needle or other piercing element of the filling device that pierces through thesecond layer28 and into one of the first andsecond filling chambers22a,22bin a fluid-tight manner. The sharp filling object may comprise a tube (e.g., a capillary tube) that is connected in fluid communication with a first constituent or beneficial agent. Thesecond layer28 may form a fluid-tight seal with the tube while the tube is positioned in flow communication with one of the first andsecond filling chambers22a,22b.
• This last arrangement may be particularly beneficial as thepackage10 is hermetically sealed prior to the introduction of the constituent or beneficial agent, which can be performed on a different portion of the manufacturing line or on a different line. Thepackages10 may be stacked between the sealing step and the filling step. In one arrangement, a rubber or semi-rigid sealing member is disposed within at least one of the first andsecond filling chambers22a,22b,thereby forming an interface with the filling device to facilitate the sealing of the filling members coupled to thepackage10. In at least one example, the cross-sectional shape and size of the first andsecond filling channels24a,24bmay be sufficiently small to prevent the substance filled into thefirst compartment20afrom returning out through the first andsecond filling channels24a,24bdue to surface tension or particle size of the substance.
• In one arrangement, a check valve is disposed in at least one of the first andsecond filling chambers22a,22bto control the flow of a substance into thefirst compartment20a.A semi-permeable object may be disposed in at least one of the first andsecond filling chambers22a,22band the first andsecond filling channels24a,24bto allow gases to escape during filling and prevent the substance from leaving thefirst compartment20aby backflow. In one arrangement, the flow evacuating thefirst compartment20aduring filling is monitored and filling is discontinued when the evacuated fluid switches from gas to the filling substance. A sensor may be positioned in or adjacent to one of the first andsecond filling channels24a,24bor the fillingchambers22a,22b,for detecting presence of the substance being filled into thefirst compartment20a.The sensor may indicate that thefirst compartment20ais filled. The sensor may comprise electrodes disposed on the first orsecond layer26,28, in the layers or between thelayers26,28. The electrodes and associated sensing circuitry may be configured to sense conductivity of the fluid in the second or evacuating fillingchamber22b,or change in capacitance of the media in a channel or a chamber. An example sensor arrangement is shown inFIGS. 24a-24cand described below.
• The first filling channel24amay be configured to direct the substance entering thefirst compartment20bto move along thesecond layer28 in a way that limits jetting that may result in undesirable bubbles or foaming being formed in the substance filling thefirst compartment20a.A dedicated flow deflector may be disposed in one of the first andsecond filling channels24a,24bor in one of the first andsecond filling chambers22a,22bto facilitate the gliding of the filled substance on the wall of thesecond layer28.
• In one arrangement thepackage10 is molded as a single body to the configuration shown inFIGS. 1a-1bby, for example, blow molding or gas assist molding.
• Thepackage10 may be sealed after being filled by sealing closed the first andsecond filling channels24a,24bfrom the open construction ofFIGS. 1a-1dto the closed or sealed arrangement ofFIGS. 1eand1f.The first andsecond filling channels24a,24bmay be changed from the open construction ofFIGS. 1aand 1dto the closed or sealed arrangement ofFIGS. 1eand1f.The first andsecond filling channels24a,24bmay be depressed and welded to completely seal the substance within thefirst compartment20a.The sealing temperature used to seal closed the first andsecond filling channels24a,24bmay be higher than the temperature used to form the first and secondfrangible seal portions30,32, thereby avoiding rupture of the first andsecond filling channels24a,24b(hereafter sometimes referred to as permanent seal verses frangible seal). In one arrangement, this sealing step is further applied to the circumference of thepackage10 to create the permanent seal38 described above to at least some of the areas where the frangible seal is unwanted.
• A sealable insert (e.g., insert150 shown inFIG. 4) may be disposed in the first andsecond filling channels24a,24bto facilitate sealing of the channels. The sealable insert may comprise of material with a lower melting temperature than the first andsecond layers26,28. The material of the sealable insert may be adherable to the surfaces of the first andsecond layers26,28 that form the first andsecond filling channels24a,24bto enhance the seal provided within the first andsecond filling channels24a,24bduring the sealing step. A sealable insert may be disposed in at least one of the first andsecond filling channels24a,24band in at least one of the first andsecond filling chambers22a,22bto provide at least a portion of a flow control device. The flow control device may be one of, for example, a valve (e.g., an isolation valve or check valve), a flow or pressure regulator, a flow or pressure restrictor, or a flow deflector.
• After thepackage10 is sealed to seal closed thefirst compartment20awith the constituent or beneficial agent retained therein, thepackage10 may be trimmed.FIG. 1fshows thepackage10 trimmed by methods known in the art such as, for example, punching, ruler steel cutting, laser cutting, etc. At least the first andsecond filling chambers22a,22bmay be removed from thepackage10 during the trimming step. Additional portions of the first andsecond layers26,28 may be trimmed to reduce an outer profile of thepackage10. Thepackage10 may be trimmed along the sealed portion of the first andsecond filling channels24a,24b.
• FIG. 1gshows another example package10athat does not include thefitment36 or thefitment cavity46 formed in thefirst layer26. The package10ahas been filled, sealed, and trimmed to provide the shape shown inFIG. 1g.
• It should be understood to those of skill in the art that the order of manufacturing steps disclosed above may be rearranged in whole or in part to best suit a particular design, application, and applicable manufacturing equipment. It should also be understood to those of skill in the art that additional manufacturing steps may be performed prior to, in between, and after the steps described with reference toFIGS. 1a-1f.
• Thefitment36 may be secured to (e.g., welded) and positioned between the first andsecond layers26,28. Thefitment36 may be secured to thepackage10 prior to or during the step of forming the first and secondfrangible seal portions30,32 or during the step of forming the permanent seal38. Thefitment36 may be secured to thepackage10 in any subsequent step by one of the fitment connecting methods known in the art including, for example, heat stake welding, impulse welding, vibration, ultrasonic, RF welding, and light beam welding.
• FIG. 2ashows a first welding step of securing the first andsecond layers26,28 together to form thepackage10. The seal pattern may completely circumscribe the first andsecond compartments20a,20b,the first andsecond filling chambers22a,22b,and the first andsecond filling channels24a,24b.In this first welding step, the welding is provided with a frangible seal type connection. The subsequent location of the first and second fillingports34a,34bmay be marked so that the first and second fillingports34a,34bmay be formed at a later manufacturing step (e.g., seeFIG. 2b). The first welding step may provide a hermetic seal that hermetically seals the first andsecond compartments20a,20b,the first andsecond filling chambers22a,22b,and the first andsecond filling channels24a,24b.FIG. 2bshows thepackage10 after the access area has been penetrated by a piercing member at first and second fillingports34a,34bopposite to the first andsecond filling chambers22a,22b.This step is typically done by an automated filling system.
• The portion ofpackage10 through which the first andsecond filling chambers22a,22bare accessed may be referred to as an access region or a penetrable access region. The access region may include the first andsecond access regions34a,34b.The access region may be resealable. The access region may provide a sealed interface with a device that accesses the first andsecond filling chambers22a,22bthrough the access region.
• FIG. 2cillustrates a further welding step in which a permanent seal is formed. The permanent seal38 is formed around an entire periphery of the first andsecond compartments20a,20band the area in which the first and secondfrangible seal portions30,32 are defined adjacent to the first andsecond compartments20a,20b.The permanent seal pattern38 surrounds the first andsecond compartments20a,20band overlaps most of the frangible seal pattern formed in the first welding steps shownFIG. 2a, leavingfrangible seals30 and32 unchanged. The first and second fillingports34a,34bat the access regions may be formed prior to filling or as part of filling thepackage10, and may be performed prior to or after the second weld step to form the permanent seal38, however thechannels24a,24b,would typically be sealed after the filling chamber has been used for filling or removing material from the package. In one example, the second weld step to form the permanent seal may also seal closed the first andsecond filling channels24a,24b.As such, it may be beneficial to provide the permanent seal in the second welding step after filling the first andsecond compartments20a,20b(e.g., filling thefirst compartment20ausing the filling methods described above).
• Referring now toFIGS. 3a-3f,anotherexample package100 is shown including acompartment120, a fillingchamber122, a fillingchannel124, first andsecond layers126,128, afrangible seal130, and afitment136.FIGS. 3a-3fillustrate filling steps of a method of filling thepackage10. Thepackage10 includes thefirst layer126 having a plurality of features formed therein such that when the first andsecond layers126 and128 are connected together thecompartment120, fillingchamber122, and fillingchannel124 are defined. The fillingchannel124 provides flow communication between thecompartment120 and the fillingchamber122.FIG. 3ashows thepackage100 prior to filling, wherein thecompartment120, fillingchamber122, and fillingchannel124 are integrally sealed to provide a hermetically sealed package. Thepackage100 may be sterilized by, for example, heat, radiation, or other sterilizing methods.
• FIG. 3billustrates thepackage100 having a fillingdevice102 that is engaged with thepackage100. The fillingdevice102 includes a fillingtube104 having a piercing feature at its distal end for piercing thesecond layer28 of thepackage100. The fillingdevice102 is engaged with thesecond layer28 in a fluid-tight fashion, and defines a access region where the fillingtube104 pierces thesecond layer128 to gain access to the fillingchamber122. The fillingtube104 and the access region may be disinfected prior to engagement to further reduce contamination risks for thepackage100. In one arrangement, thepackage100 and thefilling device102 are disinfected using, for example, hydrogen peroxide.
• FIG. 3cillustrates the fillingdevice102 starting the process of filling thepackage100. The fillingchannel124 directs a fluid106 along an inner surface127 of thesecond layer128. Directing the fluid106 along the inner surface127 may reduce jetting, bubbles and foaming of thefluid106.
• FIG. 3dillustrates a subsequent step in the filling process when thepackage100 is about half full. The fluid106 continues to flow along the inner surface127 of thesecond layer128 and avoids jetting and reduces bubbles, foaming and mixing of thefluid106. A gas content within thepackage100 may be evacuated through the fillingchamber122 or through a separate filling chamber and filling channel that is in flow communication with thecompartment120.
• FIG. 3eillustrates thecompartment120 completely filled and sealed. A sealing device (not shown) may collapse and thermally seal the fillingchannel124. In one arrangement, the fillingchamber122 is squeezed prior to sealing the fillingchannel124 to transfer the fluidic content of the fillingchamber122 into thecompartment120. In another arrangement, the fluidic content of the fillingchamber122 is sucked back into the fillingdevice102 via the fillingtube104 after sealing the fillingchannel124.
• FIG. 3fshows thepackage100 after thefilling device102 is retracted and the fillingchamber122 is trimmed from thepackage100. Thefitment36 may be connected to a delivery device, such as one of the syringes shown in the figures. Thefrangible seal130 may be ruptured to provide flow communications between thecompartment120 and thefitment136. Thefrangible seal130 may be ruptured by increasing pressure within thecompartment120, for example, by applying a compression force to an exterior of thecompartment120.
• Referring now toFIG. 4, another arrangement of a portion of a package110ais shown having first and second inserts150a,152adisposed in the filling chamber122aand filling channel124a.The first insert150amay serve as a seal to enhance a fluid-tight seal between the filling device102aand the package110a.The second insert152amay include an internal channel154aand an outlet155aconfigured to direct the fluid106ato the compartment120aonto an inner surface of the second layer of the package110a.In one arrangement, at least one of the first and second inserts152a,152bincludes a low melting temperature material that adheres with the first and second layers of the package110a.During the step of sealing the compartment120a,the second insert152amay melt, collapse, and seal the filling channel124a.
• Referring now toFIGS. 5a-5d,anotherexample package210 is shown in use with adelivery device212 as part of adelivery assembly200. Thedelivery device212 may include a Luer syringe that includes a piston and barrel syringe arrangement with aneedle215 for delivering medication. The delivery device also includes abarrel213, aplunger214, and acap216. Thepackage210 may be connected to thedelivery device212 with an aseptic engagement. Thedelivery device212 may be removable from thepackage210.FIGS. 5a-5cshow thepackage210 having asingle compartment220 configured to a beneficial agent or a constituent thereof. The beneficial agent or constituent thereof may have been activated to form a dose that can be drawn into thedelivery device212 via theneedle215. Thepackage210 may include abody256 having anopening258 that receives thedelivery device212 to provide flow communication between thepackage210 and thedelivery device212.
• Thepackage210 also includes first and second filling chambers222a,222band first andsecond filling channels224a,224bthat provide flow communication between thecompartment220 and the first and second filling chambers220a,220b.Thepackage210 may also include afrangible seal230 that is openable to provide flow communication between thecompartment220 and theneedle215 of thedelivery device212.FIG. 5bshows thefrangible seal230 closed.FIG. 5cshows thefrangible seal230 opened.
• Similar configurations may be operative with other needle arrangements known in the art including, for example, syringes with catheter, needle with protective soft sheathe, intramuscular (IM) needle, subcutaneous (SQ) needle, intradermal (ID) needle, micro needle, safety needles, retractable needles, irrigation needles, and applicators.
• Thedelivery device212 may include thecap216 that provides an aseptic closure to the space between thebarrel213 andplunger214. Thecap216 may help maintain thedelivery device212 as a sterile syringe assembly without the need of a sterile overwrap.FIG. 5dshows thecap216 removed with thedelivery device212 filled and removed from thepackage210. In at least some arrangements, thepackage210 anddelivery device212 may be generally referred to as a package or a package having delivery capability.
• Referring now toFIGS. 6a-6c,anotherexample package310 is shown including first andsecond compartments320a,320b,first, second, third and fourth filling chambers322a-322d,and first, second, third and fourth filling channels324a-324d.Package310 also includes first and secondfrangible seal portions330,332 and afitment336.FIG. 6cshows a cross-section view of the filling chambers322a-322d.The filling chambers are integrally sealed between first andsecond layers326,328 of thepackage310. Thepackage310 may be sealed empty or filled with air or gas (e.g., Nitrogen). Thepackage310 may be made in an aseptic fashion from sterile components. Alternatively, thepackage310 may be sterilized after formation using, for example, gamma irradiation or e-beam or autoclave. In one example, at least a portion of thesecond layer328 comprises a material that is semi-permeable to gas that allows sterilization of thepackage310 using a gas such as ETO. An example of such a semi-permeable material is Tyvek.
• FIG. 6bshows thepackage310 after filling, sealing, and trimming has occurred. The first, second, third and fourth filling channels324a-324dare sealed closed and a sacrificedportion321 carrying the first, second, third and fourth filling chambers322a-322dis removed. Thefitment336 may be connected to a delivery device such as a syringe to deliver contents of the first andsecond compartments320a,320b.
• FIGS. 6dand 6eillustrate methods of filling thepackage310. A fillingdevice302 comprises a plurality of filling tubes304a-304din the form of hollow needles is shown. The filling tubes304a-304dpierce through thesecond layer328 to establish fluid communication with the filling chambers322a-322d.A fluid-tight seal may be formed between thesecond layer328 and the filling tubes304a-304d.In one example, afirst filling tube304amay communicate with a first filling chamber322ato deliver a first constituent to thefirst compartment320avia a first filling channel324a.Asecond filling tube304bcommunicates with a second of the fillingchambers322bto exhaust gases from thefirst compartment320aduring filling of thefirst compartment320awith a first constituent.
• Vacuum may be applied at thesecond filling tube304bto facilitate the filling process. In some arrangements, counter pressure is applied to theexhaust filling chamber322bto inflate theconstituent compartment320aduring filling to maximize its holding volume. Similarly, thefirst compartment320amay be inflated by applying flow resistance in thesecond filling channel324b,thesecond filling chamber322b,thesecond filling tube304b,or elsewhere in the exhaust line. In one arrangement, thefirst compartment320ais inflated to its maximum holding volume by applying a vacuum external to thesecond filling chamber322b.Thecompartment320amay be held in a shaped mold while the vacuum is applied to define the inflatedfirst compartment320ashape while applying the vacuum.
• Thepackage310 may be tilted during filling such that theexhaust filling channel324bandexhaust filling chamber322bare elevated relative to the filling channel324aand filling chamber322ato allow all gases to exit out of thefirst compartment320abefore the constituent reaches theexhaust filling channel324b.An artificial gravity field may be applied by centrifuge motion. A detector may be embedded in thefilling device302 or in thepackage310, or elsewhere to sense that thefirst compartment320ais adequately filled and to indicate to halt the filling process.
• In one arrangement, thepackage310 is depressed against the fillingdevice302 by applying force with a body against thefirst layer326. In other arrangements, a surface of thefilling device302 comprisesvacuum grooves303 arranged adjacent to thepackage310 and in communication withvacuum ports305a,305b.The applied vacuum helps hold thepackage310 against the fillingdevice302.
• An additional sealing member may be disposed in the filling chambers322a-322dto enhance the aseptic seal between the fillingdevice302 and thepackage310. An environment around thepackage310 may not necessarily be aseptic or required to be aseptic because the internal compartments, chambers and channels of thepackage310 were previously integrally sealed during the process of forming thepackage310. Contamination or foreign particles may be avoided from the fillingdevice302 and associated filling tubes304a-304dby locally maintaining these objects and the portions of thepackage310 to interface with the fillingdevice302 as clean and disinfected. Dry wiping, wiping with alcohol, UV radiation, infrared radiation, heat, freezing, spraying, puffing, brushing, and local depyrogenation are some of the techniques that may be applied, individually or combined, to prevent foreign particles from being introduced into thecompartment320aas a result of the filling tubes304a-304dpiercing thesecond layer328.
• The filling channels324a-324dmay be designed such that the constituent flows along an inner surface of the second layer322 within thecompartment320a,320bby moving (e.g., gliding) along the inner surface thereby limiting undesirable jetting and foaming. A nozzle or other insert may be disposed in at least one of the fillingchambers322a,322cand filling channels324a,324cto enhance a desired flow pattern in thecompartments320a,320b.A valve or other regulator may be disposed in one of the fillingchambers322a,322cand filling channels324a,324cto control the flow to thecompartments320a,320b.Similar valves or regulators may be positioned in the outlet orexhaust filling chambers322b,322dand fillingchannels324b,324dto help provide flow control.
• The arrangement ofFIGS. 6dand 6emay provide concurrent filling and exhausting of both of thecompartments320a,320b.The elevated, angled orientation of thepackage310 and fillingdevice302 shown inFIGS. 7aand 7bmay help remove gases from thecompartments320a,320bduring filling.
• The arrangement ofFIGS. 6dand 6emay also be useful for lyophilizing a constituent in thecompartments320a,320b.In one example, the first constituent is introduced through the fillingchambers322a,322c,and humidity and pressure in thecompartments320a,320bare controlled through theexhaust filling chambers322b,322d.Filling of the constituent may be performed in one dose or in multiple smaller doses. Filling using multiple smaller doses may allow for better surface evaporation and also allow for more efficient filling of thecompartments320a,320bwith a lyophilized cake. Temperature may be controlled by controlling heat transfer through the first andsecond layers326,328, either by introducing the package in a lyophilizer or a controlled environment chamber, or by locally pumping heat to and/or from the first andsecond layers326,328. Because the package is aseptically sealed, the lyophilization environment may not necessarily be aseptic.
• The filling channels324a-324dmay be sealed closed by heat welding across all of the filling channels324a-324das shown inFIG. 6b. The filling channels324a-324dmay collapse so that thefirst layer326 is joined with thesecond layer328 to form a permanent closure. Inserts may be disposed in the filling channels324a-324dto facilitate an improved seal. In one arrangement, the inserts may at least partially melt during heat sealing. In one arrangement, the sealing is achieved by bringing the heating element and a counter surface in contact with opposing sides of thepackage310. The fillingdevice302 may comprise the heating element or the counter surface. In one arrangement, the heating element is embedded intopackage310 such as in the first orsecond layers326,328, or therebetween. Once the filling channels324a-324dare sealed, the filling chambers322a-322dare removed as shown inFIG. 6b. Residue of the constituents delivered to the first andsecond compartments320a,320bmay be evacuated either into the first andsecond compartments320a,320bor drawn out of the filling chambers322a-322band filling channels324a-324dprior to or during the process of sealing closed the filling channels324a-324d.
• Referring now toFIGS. 7a-7c,thepackage310 may include abacking356 and outer sealing members360a-360daligned with each of the filling chambers322a-322d.The sealing members360a-360dseal around the filling tubes304a-304das they are inserted into the filling chambers322a-322d.The sealing members360a-360dmay comprise a semi-rigid polymer or elastomer or a combination thereof. In some arrangements, thesecond layer328 may include pre-formed holes that are sealed closed by the sealing members360a-360dand ready to receive the filling tubes304a-304das the filling tubes are inserted through the sealing members360a-360d.
• FIG. 7billustrates an arrangement wherein thebacking356 includes through-holes357a-357d.The through-holes357a-357dmay help align the filling tubes304a-304dwith the filling chambers322a-322d.A portion of thebacking356 may remain between the through-holes357a-357dand thesecond layer328 to maintain the filling chambers322a-322dsealed closed. Thebacking356 may be configured to be pierced and may comprise, for example, a pierceable membrane designed to seal around the intruding filling tubes304a-304d.
• FIG. 7cshows a plurality of internal sealing members362a-362dpositioned within the filling chambers322a-322d.The internal sealing members362a-362dmay provide an additional fluid-tight seal between the filling tubes304a-304dand thepackage310 during filling. The internal sealing members362a-362dmay also provide improved closure of the filling chambers322a-322dupon removal of thefilling device302. The sealing members362a-362dmay be joined in a fluid-tight fashion such as by heat welding to the first orsecond layer326,328. Thesecond layer328 may include ports or through-holes pre-formed therein for receiving the filling tubes304a-304d.
• Referring now toFIGS. 8a-8f,anotherexample package410 is shown including acompartment420, first, second and third filling chambers422a-422c,and first, second and third filling channels424a-424c.Thepackage410 also includes first andsecond layers426,428, afitment cavity446, afitment opening429 formed in thesecond layer428, and afitment436 having a flange portion468, aprotrusion465 having aninternal conduit469, achannel466, and a knockoff portion467 (seeFIG. 8e).
• Thechannel466 of thefitment436 provides fluid communication with the interior of thecompartment420. Thefitment436 is positioned between the first andsecond layers426,428. Theflange portion464 retains thefitment436 between the first andsecond layers426,428. Theprotrusion465 extends through thefitment opening429. A fluid-tight seal is provided between the first andsecond layers426,428 and theflange portion464 andprotrusion465. Theprotrusion465 is configured to join with a fluid passageway of a dispensing system, a backing, or other external device. A force may be applied to theflange portion464 through thefirst layer426 when joining thepackage410 with an external device. In one arrangement, ultrasonic vibration, combined with axial force, is directed to theflange portion464 to ultrasonically weld theprotrusion465 to an external device. Other joining methods known in the art may be used to connect thefitment436 to an external device including, for example, gluing and adhesion.
• Thechannel466 in theflange portion464 may allow the constituent to flow from thecompartment420 to an outlet of thefitment436. Afrangible seal430 may be provided between thecompartment420 and thechannel466.
• Theknockoff portion467 may be optionally provided at a distal end of theprotrusion465. Theknockoff portion467 may help maintain thechannel466 aseptically sealed. Theknockoff portion467 may be removed prior to usage of thepackage410 or prior to integrating thepackage410 with an external device. Alternatively to use of theknockoff portion467, thefitment436 may be aseptically sealed with a twist-off closure, a flip-off closure, a plug, a cap, an adhered foil, or a welded foil.
• In one example, the first and second filling channels424a-424bmay be used to fill thecompartment420 by providing filling and exhausting as described above with previous examples. The first and second filling channels424a-424bmay be sealed at the end of the filling process after thecompartment420 is completely filled. Athird filling chamber422candthird filling channel424cmay be used at a later stage to establish communication of a device with the content ofcompartment420 by accessing (e.g., piercing) thethird filling chamber422c.Thethird filling channel424cmay be permanently sealed at the end of this later stage access of thecompartment420 via thethird filling chamber422c.In one arrangement, thethird filling chamber422cmay be used to sample the constituent held in thecompartment420 or to measure a property of that constituent or product in thecompartment420. In another example, thethird filling chamber422cand associatedthird filling channel424cmay be used to add a substance such as a third constituent to thecompartment420. In another example, thethird filling chamber422cand associatedthird filling channel424cmay be used to remove a substance from thecompartment420. In a still further example, thethird filling chamber422cand associatedthird filling channel424cmay be used to remove moisture from thecompartment420. Other example packages may include any number of additional filling chambers and filling channels that are used in subsequent steps to access thecompartment420 after thecompartment420 has been filled via the first and second fillingchambers422a,422band first andsecond filling channels424a,424b.
• According to one example, third and fourth filling chambers may be used to add a constituent to thecompartment420. This arrangement may be advantageous as thecompartment420 is integrally sealed after filling thecompartment420 with a first constituent, and a second constituent is filled via the third and fourth filling chambers at a later stage, such as on a different filling system or in the field of use by a user. In another example, third and fourth filling chambers and third and fourth filling channels may be used to drive a fluid through thecompartment420 to cause fluid exchange in thecompartment420. In a still further arrangement, a third filling chamber and associated third filling channel may provide injection of dry air or inert gas into thecompartment420, and a fourth filling chamber and associated fourth filling channel may be used to recover moist air from thecompartment420.
• In another example, a filling chamber and filling channel may introduce gas to a liquid phase constituent that is sealed within thecompartment420 at an entry point below the surface of the liquid constituent's surface within thecompartment420, and a further filling chamber and associated filling channel may be used to evacuate gas from thecompartment420 at a point above the liquid level of the constituent within thecompartment420. As is evident from these examples, a plurality of filling chambers and filling channels may be used to formulate a constituent in thecompartment420 during or after filling of the compartment and sealing the compartment. The introduction of, for example, light, heat, radiation, vibration, cooling or a combination thereof may be provided through one of the first andsecond layers426,428. A heating element may be implemented in the first andsecond layers426,428. In one example, a heating element is embedded in thesecond layer428.
• In another example manufacturing process, a plurality ofpackages410 are made on a web format as illustrated inFIG. 11, and a plurality of heating elements of neighboringpackages410 on the web may be connected in parallel. In one such arrangement, the heating element is a thin registered conductive layer joined to a nonconductive laminate. In one example, a conductive laminate of thesecond layer428 is used as a heating element. Electrodes may be connected to the ends of a large web format comprising a plurality ofpackages410 and heat cavities by conducting electric current through the conductive layer. A package having at least one heating element is shown and described with reference toFIGS. 24a-24c.
• FIG. 8fshowssemi-permeable wall portion425 aligned with at least one of the filling chambers424a-424c.Thesemi-permeable wall portion425 may provide an access region for insertion of a filling member (e.g., fillingtube104 ofFIGS. 3a-3f) through thesecond layer428 and into one of the filling chambers424a-424c.
• Thepackage410 may be accessed to remove material or introduce material from thecompartment420. In one example, the first and second fillingchambers422a,422bare accessed via thesemi-permeable wall portion425 for at least one of removing material (e.g., removing gas or removing a sample of the beneficial agent or constituent thereof) and introducing material (e.g., the beneficial agent or constituent thereof) from thecompartment420 or at least one of the first and second fillingchambers422a,422b.
• The forming ofpackage410 may be completed prior to accessing at least one of the first and second fillingchambers422a,422bto fill or remove content from thecompartment420. The forming ofpackage410 may occur currently with accessing thepackage410. The forming ofpackage410 may occur concurrently with any one of filling thepackage410 and sealing thepackage410.
• FIG. 9 shows an arrangement of a package410awherein afirst compartment420aand asecond compartment420bshare acommon filling chamber422b.FIG. 10 shows anotherexample package410bin which each of thecompartments420a,420bof a single package comprise asingle filling chamber422a,422b,respectively, and asingle filling channel424a,424b,respectively. Each of thecompartments420a,420bmay include a separatefrangible seal portion430,432, respectively.
• Referring again toFIG. 11, a plurality of first layers of a plurality ofpackages310 are formed of a single sheet of web material. The compartments, filling chambers and channels are formed in the first layer. The web advances in a production line to receive the second layer and a fitment. Filling of thecompartments320a,320binpackages310 may be performed simultaneously for a plurality of thepackages310. In one arrangement, adjacent cavities of separate packages on theweb307 may share a filling chamber322aas shown inFIG. 12a. Separate fillingchannels324aand324dmay provide flow communication between the filling chamber322aandseparate compartments320a,320bonadjacent packages310. Alternatively, the adjacent compartments may be on the same package. In one example, an exhaust filling chamber may communicate with a plurality of compartments. Thepackages310 may be arranged inrows308 andcolumns309 on theweb307.
• In another example, a joined communication channel or bus may communicate with multiple filling chambers for multiple packages as shown inFIG. 12b.FIG. 12billustrates an arrangement where a plurality of fillingchannels324a,324dassociated withadjacent compartments320a,320bare in communication via abus channel305 that provides flow communication between a plurality of (to be formed) packages310.
• FIGS. 13a-13fare flow diagrams showing example methods of creating a filled, sealed package in accordance with the various teachings provided herein.FIG. 13ashows amethod500aof first forming the package at501, sealing the package at502, sterilizing the package at503, filling the package at504, and singulating the packages from each other at505.
• FIG. 13bshows amethod500bof first forming the package at511, sealing the package at512, sterilizing the package at513, singulating the packages from each other at514, and filling the packages at515.
• FIG. 13cshows anexample method500cthat includes first forming the package at521, sealing the package at522, singulating the packages from each other at523, sterilizing the packages at524, and filling the packages at525.
• FIG. 13dshows amethod500dthat includes forming a package at531, sealing the package at532, joining the packages to a device at533, sterilizing the package (and the device) at534, singulating the packages from each other at535, and filling the packages at536.
• FIG. 13eshows anexample method500ethat includes forming a plurality of packages at541, sealing the packages at542, joining the packages to a device at543, sterilizing the packages at544, filling the packages at545, and singulating the packages at546.
• FIG. 13fshows anexample method500fthat includes forming a plurality of packages at551, sealing the packages to at least one device at552, singulating the packages at553, filling the packages at554, and sterilizing the packages at555.
• FIGS. 14a-14fshow anotherexample package610 in the form of a cartridge. The cartridge includes abarrel664, aplunger666, aplunger core668, and abarrier670 positioned at a proximal end of theplunger core668. Thepackage610 defines acompartment620 and may be sealed at its distal end with anend seal665. Theplunger666 andplunger core668 define first and second fillingchambers622a,622band first andsecond filling channels624a,624b.Thebarrel664 may comprise, for example, glass or polymer such as polyethylene, polypropylene, COC, COP, or polycarbonate.
• FIG. 14bshows theplunger core668 positioned within theplunger666. The plunger core may include a thermoplastic material. Thebarrier670 may maintain thepackage610 aseptically sealed prior to filling. Thebarrier670 may comprise any desired material including, for example, a film, foil, molded plastic or rubber, or a combination thereof. Thepackage610 may be sterilized using, for example, heat or irradiation.
• FIGS. 14cand 14dillustrate thepackage610 during filling. A fillingdevice602 having first andsecond filling tubes604a,604bmay be connected to thepackage610. The fillingtube604a,604bmay pierce through thebarrier670 to establish fluid communication with thecompartment620 via the first and second fillingchambers622a,622band the first andsecond filling channels624a,624b.In one arrangement, the fillingtube604ais used to deliver a drug or other beneficial agent into thecompartment620 and thesecond filling tube604bis used to exhaust or draw air or other gases from thecompartment620 prior to or during filling.
• The fillingtubes604a,604bmay seal against thebarrier670 to maintain thepackage610 aseptically sealed during filling. In one example, thebarrier670 comprises a multilayer foil having at least first andsecond layers670a,670b,as illustrated inFIG. 14d. Thesecond layer670bmay include an elastic material that is stretched to form a sheathe or a sleeve-like seal around the filling tube when thebarrier670 is pierced by the first andsecond filling tubes604a,604b(seeFIG. 14d). During filling, a pressure within the fillingchambers622a,622brises to further tighten the seal around the fillingtubes604a,604bto limit leaking. The first layer of the barrier670amay comprise a material that is more rigid or less deformable than the inner elastic layer to help maintain the structure and rigidity of thebarrier670 to inhibit collapsing of thebarrier670 when being pierced by the fillingtubes604a,604band during filling.
• The elastic layer of the barrier670 (e.g.,layer670b) may include, for example, EVA, EAA, or PE ionomer or ionomer blend such as Easy Peel. The more rigid layer of the barrier670 (e.g., layer670a) may comprise, for example, aluminum, PET, polyester, nylon, or an oriented film.
• In at least one example, the fillingtube604a,604bmay comprise a relatively dull piercing end that promotes stretching of the inner elastic layer thereby increasing the sleeve effect of the seal672 when thebarrier670 is being pierced.
• Thepackage610 may be tilted or arranged at an angle during filling so that the air or gas in thecompartment620, which needs to be evacuated during filling, will more readily travel towards theexhaust filling channel624b.The fillingdevice102 may include a sensor for detecting when thecompartment620 is completely filled. This may be detected by sensing the presence of the liquid or other substance being delivered intocompartment620 by the fillingdevice102. When thecompartment620 is filled, it may be resealed by deforming the fillingchannels624a,624bto form a fluid-tight seal or sealedchannels648a,648bas shown inFIG. 14e. The sealedchannels648a,648bmay be formed by pinching the fillingchannels624a,624bwith heated members to form a heat seal. In other arrangements, plugs or sealing members may be disposed in the fillingchannels624a,624bto facilitate sealing. The plugs may have a cross-sectional shape that is smaller than that of the fillingchannels624a,624bto allow flow around the plugs and seal against the inner wall of the fillingchannels624a,624bas the channels are collapsed. Alternatively, the plugs may comprise at least one through-hole allowing fluid flow to and from thecompartment620 and the path into thecompartment620 is sealed when the fillingchannels624a,624bcollapse.
• The plugs may comprise a rubber material or a low melting point polymer. After sealing the fillingchannels624a,624b,the portion ofplunger666 andplunger core668 that define the fillingchambers622a,622bmay be removed as illustrated inFIG. 14fThe sealedchannels648a,648bmay maintain thepackage610 aseptically sealed.
• The arrangement ofpackage610 in a cartridge form may allow a manufacturing method wherein thepackage610 can be transferred to a filling station (or filling line or filling site) fully assembled and sterilized, thereby substantially reducing capital equipment and filling operation costs and complexity.
• In one example, theplunger666 andplunger core668 comprise a common material that provides properties advantageous for sealing thebarrel664 and heat sealing the fillingchannels624a,624b.In one example, the fillingchambers622a,622bare merely extensions of the fillingchannels624a,624b.The fillingdevice102 may seal against a wall defining the fillingchambers622a,622binstead of against abarrier670. In another example, only a single one of the fillingchambers622a,622bis included in thepackage610. In another arrangement, more than two fillingchambers622a,622bmay be provided with thepackage610 for simultaneous or consecutive delivery of several substances to thecompartment620. In one example, only asingle filling channel624a,624bis provided in the device. In other examples, more than two fillingchannels624,624bare provided such that several substances may be filled simultaneously or consecutively into thecompartment620.
• In one arrangement, at least one filling chamber is sealed with a semi-permeable material to allow sterilization of thecompartment620 using sterilization fluid such as, for example, ETO or HPV. In one example, the fillingchambers622a,622bare sealed with a sealing component such as a rubber seal instead of or in addition to thebarrier670. A vacuum system may be used to attach thefilling device102 to the package610 (e.g., against the barrier670). The use of vacuum may help prevent leakage between the fillingdevice602 and thepackage610. In one example, the substance (drug) remaining in theplunger666 andplunger core668 after sealing the fillingchannels624a,624bmay be withdrawn by the fillingsystem602. Thepackage610 may be maintained under vacuum prior to piercing of thebarrier670 with thefilling system602 to facilitate delivery of the substance (e.g., drug) into thecompartment620.
• Referring now toFIGS. 15a-15b, anotherexample package710 is shown including many of the same or similar features as described above with reference topackage610. Thepackage710 includes abarrel764,plunger766 andplunger core768. Thepackage710 may define acompartment720 and may be sealed at its distal end with anend seal765. Theplunger766 andplunger core768 may define first and second fillingchambers722a,722b,first andsecond filling channels724a,724b,first and second filling bores774a,774b,and first andsecond passageways775a,775b.
• Theplunger core768 may be movable in an axial direction relative to theplunger766 from a first position wherein the first andsecond passageways775a,775bfrom the fillingchannels724a,724bthrough the filling bores774a,774bto thecompartment720 are open, to a second position wherein the first andsecond passageways775a,775bare sealed closed.
• The filling bores774a,774bmay be sized to receive distal tips of theplunger core768 within which the fillingchannels724a,724bare formed. Advancing theplunger core768 relative to theplunger766 seals closed fluid flow into thecompartment720. Retracting theplunger core768 relative to theplunger766 opens thecompartment720 in flow communication with the fillingchambers722a,722b.
• FIG. 15ashows thepackage710 prior to filling.FIG. 15bshows thepackage710 during filling as fillingtubes704a,704bof afilling system702 pierce through thebarrier770. Theplunger core768 is in a first position allowing fluid communication between the fillingsystem702 and thecompartment720. When filling of thecompartment720 is completed, theplunger core768 is advanced to the second position shown inFIG. 15c. The outer wall of theplunger core768 seals with the filling bores774a,774bwithin theplunger766 to form the seal.FIG. 15dshows thepackage710 after thefilling system702 has been removed and thecompartment720 is filled and aseptically sealed. In this arrangement, the fillingchannels724a,724bdo not need to be separately sealed using, for example, a heated member that compresses and seals closed the filling channels.
• Thepackage710 may be operable between sealed and unsealed states or conditions using a linear or axial actuation of theplunger766 relative to theplunger core768. The seal interface may occur within thebarrel764. Other arrangements are possible in which the seal is formed by relative movement between theplunger766 and thebarrel764, or between theplunger core768 and thebarrel764. The seal may be maintained by an interference fit between portions of theplunger766 andplunger core768. Once moved into the sealed or second position, theplunger core768 may be fixed in the sealed position and not be capable of removing to the first or unsealed position relative to theplunger766.
• FIGS. 15b, 15cand 15eshow an additional sealing interface between the fillingtubes704a,704band thepackage710. The fillingchambers722a,722bmay have a tapered shape that provides contact between theplunger core768 and distal end portions of the fillingtubes704a,704bto provide adistal seal771. Thedistal seal771 may be a fluid tight seal that is formed in place of or in addition to the seal provided between thebarrier770 and the fillingtubes704a,704b.In at least some embodiments, thedistal seal771 is provided between distal end portions of the fillingtubes704a,704band the fillingchannels724a,724b.The arrangement of the fillingtubes704a,704bshown inFIGS. 15b, 15cand 15emay be referred to as a double sealing or double piercing arrangement for accessing the fillingchambers722a,722b.
• Referring now toFIGS. 16a-16f,apackage810 is shown having many of the same or similar features as thepackages610,710 described above, but is configured to provide sealing of the compartment using a rotational motion.
• Thepackage810 includes abarrel864, aplunger866, aplunger core868, abarrier870, and anend seal865. Thebarrel864 andplunger866 may define acompartment820. Theplunger866 andplunger core868 may define first and second fillingchambers822a,822b,first andsecond filling channels824a,824b,and first andsecond passageways875a,875b.Theplunger core868 may rotate relative toplunger866 to open and close access to thecompartment820 by closing the first andsecond passageways875a,875b.In a first position, theplunger core868 leaves open the first andsecond passageways875a,875bfrom the fillingchambers822a,822b,through the fillingchannels824a,824band into thecompartment820, as shown inFIGS. 16a-16c.Theplunger core868 is rotatable into a closed position shown inFIGS. 16dand 16ein which the fluidic passageway is closed to seal thecompartment820.
• FIGS. 16aand 16bshow thepackage810 in a pre-filled, aseptically sealed configuration. Theplunger866 is in a first position wherein the fillingchannels824a,824bprovide flow communication between the fillingchambers822a,822band thecompartment820.FIG. 16cillustrates thebarrier870 being pierced by filling tubes804a,804bof afilling device802 to deliver a substance intocompartment820.
• FIGS. 16dand 16eshow theplunger core868 in a closed position after filling thecompartment820 is completed. Theplunger core868 has been rotated relative to theplunger866 so that theplunger core868 seals thecompartment820. Many other types of rotational seals may be possible for controlling fluid flow from the fillingchambers824a,824bto thecompartment820.
• FIG. 16fshows thepackage810 having abarrier870 having askirt873 that extends to an outer surface of thebarrel864. Theskirt873 may provide additional sealing of thepackage810 that limits contamination from reaching the area between theplunger866 and inner surfaces of thebarrel864.
• FIGS. 17aand 17bshow anotherexample package910 wherein the package is formed using a blow molded and self-containedadministration device976 behind a removable (e.g., twist-off)cover978. Thepackage910 includes first and second fillingchambers922a,922bthat communicate with acompartment920 via first and second fillingchambers924a,924b.Thepackage910 may be blow molded around theadministration device976 with thecover978 formed integral with the remaining portions of thepackage910 with the exception of theadministration device976. Thepackage910 is one example of a package that is formed in a single molding step wherein the package is aseptically sealed and prepared for filling by a beneficial agent or constituent thereof.
• Thecompartment920 may have a billows or accordion shape that promotes delivery of the substance, which is later filled into thecompartment920 via the fillingchambers922a,922band fillingchannels924a,924b,upon application of an axial force that compresses thecompartment920 to deliver the substance out through theadministration device976.
• The first and second fillingchambers922a,922band at least portions of the first andsecond filling channels924a,924bmay be carried by asacrificial portion921 that is removed after filling thecompartment920 and sealing the first andsecond filling channels924a,924b.
• FIGS. 18a-18bshow anotherexample package1010 in the form of a syringe delivery device. Thepackage1010 includes abarrel1064 and aplunger1066 that define a compartment1020. Anadapter1021 having first and second filling chambers1022a,1022band first andsecond filling channels1024a,1024bmay be attached to the barrel and arranged in flow communication with the compartment1020 as shown inFIG. 18b. Thepackage1010 may also include anadministration device1076 enclosed within aremovable cover1078.
• Thepackage1010 may be configured as a disposable syringe. In accordance with one filling method, theplunger1066 may be retracted prior to filling to create a desired volume of the compartment1020 within thebarrel1064 to hold a desired amount of dispensable substance (i.e., beneficial agent or constituent thereof). Alternatively, theplunger1066 may be pushed back by pressure exerted by delivery of the substance into the compartment1020 via the first andsecond filling channels1024a,1024b.In one arrangement, the filling channels are sealed and the filling compartments are removed after filling the compartment1020. The first andsecond filling channels1024a,1024bmay be sealed by application of a heated sealing member or any of the other sealing methods described herein. In one example, the first andsecond filling channels1024a,1024bcommunicate with a tip of the syringe structure at the area covered by thecover1078. In some arrangements, theadapter1021 is configured to provide an interface between the tip of the syringe (i.e., at a location where theadministration device1076 is secured to the barrel1064) and the first andsecond filling channels1024a,1024b.
• FIG. 18dshows thepackage1010 ofFIGS. 18a-18chaving a detent1065 that retains theplunger1066 in a fixed axial position during filling of the compartment1020. The detent may be adjustable to release theplunger1066 to permit axial movement of theplunger1066 during delivery of the content via theadministration device1076.
• Referring now toFIGS. 19a-19e,apackage1110 is shown in the form of a dual chamber syringe for delivery of a first substance (i.e., a first beneficial agent) and a second substance (i.e., second beneficial agent) consecutively in a single linear operation of a plunger. Thepackage1110 includes abarrel1164 having first andsecond plungers1166a,1166bpositioned therein to define first andsecond compartments1120a,1120b.An adapter such asadapter1021 described above and shown with reference toFIGS. 18aand 18bmay be connected in flow communication with one or both of the first andsecond compartments1120a,1120b.Filling of thepackage1110 may be completed using one of the adapter arrangements described below with reference toFIGS. 20a-20dor21a-21d.
• Thebarrel1164 may include abypass channel1180 that provides a flow path around the first plunger1166awhen the first plunger1166ais in a distal most advanced position within thebarrel1064 as shown inFIGS. 19cand 19d. Anadministration device1176 and associatedcover1178 may be positioned at a distal end of thebarrel1164.
• Thebarrel1164 may include a distal portion1164athat is separable from the rest of thebarrel1164 as shown inFIG. 19b. The distal portion1164amay be, for example, pre-assembled with theadministration device1176 and associatedcover1178 before connection to thebarrel1164. The distal portion1164amay also include achannel1179 that provides flow communication from theadministration device1176 to thebypass channel1180 and the compartment1120.
• Thefirst compartment1120ais configured to store a first beneficial agent, and is defined in thepackage1110 between a distal end of thebarrel1164 and the first plunger1166. Thesecond compartment1120b,for storing a second beneficial agent, is defined in thebarrel1164 between the first plunger1166aand thesecond plunger1166b.
• Thepackage1110 may be formed by separately forming thebarrel1164 from a distal portion of thebarrel1164 that includes thebypass channel1180. The two portions may be formed separately and assembled together in a later step. Alternatively, thebypass channel1180 could be formed in a single step when forming the remaining portions of thebarrel1164. The portion of the barrel including thebypass channel1180 may be connected to the remaining portion of thebarrel1164 by any method known in the art including, for example, heat welding, spin welding, ultrasonic welding, RF welding, vibration welding, solvents, glues, adhesives, mechanical interface, press-fit, or via a coupler or tape. Alternatively, thebypass channel1180 may be molded on an inner wall of thebarrel1164 by applying a reciprocal ridge shape to a core of an injection mold.
• FIG. 19ashows thepackage1110 after the first and second beneficial agents have been delivered into the first andsecond compartments1120a,1120b.FIGS. 19cand 19dshow thepackage1110 after thesecond plunger1166bhas been advanced to advance the first plunger1166ato administer the first beneficial agent from thepackage1110. The first plunger1166ais positioned at a distal most portion of thebarrel1164 so that thebypass channel1180 extends from a front or distal end of the first plunger1166ato a rear or proximal end of the first plunger1166a.At this position, thebypass channel1180 establishes fluid communication between thesecond compartment1120band theadministration device1176. Further advancement of thesecond plunger1166btoward the distal end of thebarrel1164 will deliver the second beneficial agent through thebypass channel1180 to theadministration device1176. In one arrangement, the first plunger1166ais compressible and its axial length is such that thebypass channel1180 does not open to thesecond compartment1120bwhen the first plunger1166areaches the distal end of the barrel1164 (i.e., when the delivery of the first beneficial agent is completed). A further advancement of thesecond plunger1166bpressurizes the second beneficial agent within thesecond compartment1120bcausing the first plunger1166ato compress and establish fluid communication through thebypass channel1180 to theadministration device1176. This multi-stage advancement of the first and second beneficial agents is possible by not opening thebypass channel1180 until intending to deliver the second beneficial agent further reduces possibility of mixture of the first and second beneficial agents and provides a pronounced sensation to the user when switching from delivering the first beneficial agent to delivering the second beneficial agent.
• FIG. 19eshows thepackage1110 when the first andsecond plungers1166a,1166bare advanced to the distal end of thebarrel1164 and delivery of the first and second beneficial agents has been completed.
• Referring now toFIGS. 20a-20d,anotherexample package1210 in the form of a disposable syringe is described. Thepackage1210 includes abarrel1264, first and second plungers1266a,1266b,abypass channel1280, anadapter1221 having abarrier1270, first andsecond compartments1220a,1220bdefined within thebarrel1264, and first andsecond filling chambers1222a,1222band first andsecond filling channels1224a,1224bdefined within theadapter1221.
• The dual syringe arrangement of thepackage1210 may have at least some of the advantages described above with reference to thepackage1110 concerning consecutive delivery of first and second beneficial agents. Thepackage1210 includes an administration device1276 and acover1278 enclosing the administration device1276. A sealing member1277 (e.g., a rubber stopper) may be used to seal the administration device1276. The sealingmember1277 may be positioned between the administration device1276 and cover1278 as shown inFIGS. 20b-20d.Thepackage1210 may include asterile cap1216 that maintains a sterile environment within thebarrel1264 at the proximal end of thebarrel1264. The first andsecond filling channels1224a,1224bare associated with the distal end of the barrel and may provide access to the first andsecond compartments1220a,1220bwhen the first plunger1266ais positioned at a distal end of thebarrel1264 as shown inFIGS. 20band 20c. Thefirst filling channel1224acommunicates with thefirst compartment1220aand thefirst filling chamber1222a.Thesecond filling channel1224bcommunicates with thesecond compartment1220band thesecond filling chamber1222b.Thebarrier1270 aseptically seals the first andsecond filling chambers1222a,1222b.
• FIG. 20cshows afilling device1202 having first andsecond filling tubes1204a,1204bin fluid communication with the first andsecond filling chambers1222a,1222b.In one example method of filling thepackage1210, thesecond compartment1220bis first filled by delivering a beneficial agent through thesecond filling tube1204bthrough thesecond filling chamber1222bandsecond filling channel1224b.The second plunger1266bmay be retracted upon pressure created in thesecond compartment1220bby delivery of the beneficial agent into thesecond compartment1220b.Alternatively, the second plunger1266bmay be retracted prior to delivering the second beneficial agent into thesecond compartment1220b.
• FIG. 20dshows filling of thefirst compartment1220aby thefilling system1202. The first plunger1266ais typically positioned so that thebypass channel1280 is closed prior to delivering the first beneficial agent via the first filling tube1204a,first filling chamber1222a,andfirst filling channel1224ato thefirst compartment1220a.Delivering the first beneficial agent into thefirst compartment1220amay push back the first plunger1266a.As the first plunger1266ais pushed back, the second beneficial agent pushes the second plunger1266bfurther back. After the first andsecond compartments1220a,1220bare filled, the first andsecond filling channels1224a,1224bmay be sealed and theadapter1221 removed in a similar fashion as described above with reference to other embodiments disclosed herein.
• Thepackage1210 may be emptied according to, for example, the methods described above with reference toFIGS. 19a-19e.The content held inpackage1210 may be removed for testing or other purposes. Thepackage1210 may be resealed after being filled, sealed, and later accessed for removing some of the content.
• Referring now toFIGS. 21a-21d,anotherexample package1310 in the form of a disposable, dual chamber syringe is shown and described. Thepackage1310 includes abarrel1364, aplunger1366 having first andsecond plunger portions1366a,1366b,and anadapter1321. Thepackage1310 may also include anadministration device1376 that is covered by acover1378. Thebarrel1364 and first andsecond plunger portions1366a,1366bmay define first andsecond compartments1320a,1320b.Theadapter1321 may carry first, second, third and fourth filling chambers1322a-1322d,and first, second, third, and fourth filling channels1324a-1324d.Asterile cap1316 may be mounted to theplunger1366 to seal closed a proximal end of thebarrel1364 as shown inFIG. 21d.
• Thepackage1310 may be arranged in a pre-filled orientation shown inFIG. 21bwith the first andsecond plunger portions1366a,1366bpositioned at spaced apart locations within thebarrel1364. The first andsecond filling channels1324a,1324band associated first and second filling chambers1322a,1322bmay be connected to a filling device that delivers beneficial agent into the first andsecond compartments1320a,1320b.The third andfourth filling channels1324c,1324dand associated third and fourth filling chambers1322c,1322dmay be connected to a filling device that provides evacuation of gases from the first andsecond compartments1320a,1320b.The first andthird filling channels1324a,1324cmay be spaced apart axially alongbarrel1364, and the second andfourth filling channels1324b,1324dmay be spaced apart axially along thesecond barrel1364 to help promote quick and complete filling of the first andsecond compartments1320a,1320b.
• For filling, the first andsecond plunger portions1366a,1366bmay be preset in the fill position shown inFIG. 21b, thereby defining the volumes of the first andsecond compartments1320a,1320b.The first and second beneficial agents are delivered into the first andsecond compartments1320a,1320bvia the first and second filling chambers1322a,1322band first andsecond filling channels1324a,1324b.Gas is evacuated or exhausted from the first andsecond compartments1320a,1320bthrough the second andfourth filling channels1324c,1324dand the second and fourth filling chambers1322c,1322d.After the filling ofcompartments1320a,1320bis complete, the filling channels1324a-1324dare sealed and the adapters1321a,1321bare removed as shown inFIGS. 21cand 21d. The channels1324a-1324dmay be sealed to form sealed channels1348a-1348d.
• FIGS. 22a-22dshow anotherexample package1510 in the form of a vial. Thepackage1510 includes avial1582 sealed with anend seal1565 to define acompartment1520. Thepackage1510 also includes first andsecond filling chambers1522a,1522b,first andsecond filling channels1524a,1524b,and abarrier1570 that seals closed the first andsecond filling chambers1522a,1522b.Theend seal1565 may be configured as a stopper or septum through which tubes defining the first andsecond filling channels1524a,1524bpierce to obtain access to thecompartment1520. The first andsecond filling channels1524a,1524bmay be associated with a flip top cap of thevial1582 and pierce through theend seal1565, and are later removed with the flip top cover when thevial1582 is opened.
• FIG. 22dshows a filling device1502 havingfilling tubes1504a,1504bconnected to thepackage1510 with the fillingtubes1504a,1504bpiercing through thebarrier1570 to obtain access to the first andsecond filling chambers1522a,1522b.After delivery of a substance such as a beneficial agent via the filling device1502 to fill thecompartment1520, the first andsecond filling channels1524a,1524bare sealed to form first and second sealedchannels1548a,1548bas shown inFIG. 22c. The fillingchambers1522a,1522bmay be removed as shown inFIG. 22d.
• Referring toFIGS. 23aand 23b, another example package1610 is shown having a similar construction as thepackage1510 described above. Package1610 includes avial1682 andend seal1665 that define acompartment1620. Package1610 also includes first andsecond filling chambers1622a,1622b,first andsecond filling channels1624a,1624b,abarrier1670 that seals closed the first andsecond filling chambers1622a,1622b,and a biasingmember1684. The biasingmember1684 may bias the fillingchannels1624a,1624baway from theend seal1665 until it is intended to fill thecompartment1620. The biasingmember1684 may also bias the fillingchannels1624a,1624bout of thecompartment1620 and out of contact with theend seal1665 after filling thecompartment1620.
• The biasingmember1684 may be continuous with astopper crimp1667 that holds theend seal1665 assembled with the vial. The biasingmember1684 may have other constructions comprising different materials, shapes, sizes and configurations to provide a similar function of spacing apart the first andsecond filling channels1624a,1624baway from theend seal1665 and out of flow communication with thecompartment1620. The fillingchannels1624a,1624bmay be operatively moved between a first position where they do not pierce theend seal1665 and a second position where they do pierce theend seal1665.
• FIGS. 24a-24cshow anotherexample package1700 having at least one heating element operable to control a temperature of the content of thepackage1700. Thepackage1700 includes acompartment1720, first andsecond filling chamber1722a,1722b,first andsecond filling channels1724a,1724b,afrangible seal portion1730, afitment1736, first andsecond heating elements1701,1703, first andsecond heating sensors1705,1707. The first andsecond heating elements1701,1703 may control a temperature of the content held in thecompartment1720. At least one of the first andsecond sensors1705,1707 may help determine a fill level of thecompartment1720. Alternatively, at least one of the first andsecond sensors1705,1707 may help determine a temperature of the content held in thecompartment1720. The heating and sensor features ofFIGS. 24a-24cmay be used with any of the other example packages disclosed herein.
• Thepackage1700 may also include a plurality of electronic connectors ortabs1709 that provide electronic connection of thepackage1700 to an external system. Thetabs1709 may be electronically connected to the first andsecond heating elements1701,1703 and the first andsecond sensors1705,1707.
• FIGS. 25a-25eillustrate anotherexample delivery assembly1800 that includes apackage1810 and adelivery device1812. Thedelivery device1812 is in the form of, for example, a syringe having abarrel1813, a plunger (not shown), and acap1816. Thecap1816 provides a sterile and sealed proximal end of thedelivery device212 where the plunger is inserted into thebarrel1813.
• Thepackage1810 includes acompartment1820, first andsecond filling chambers1822a,1822b,and first andsecond filling channels1824a,1824b.Thepackage1810 may include a body or backing1856 arranged on a side of thepackage1810 opposite thecompartment1820. A pair of filling ports oraccess regions1834a,1834bmay be provided for accessing the first andsecond filling chambers1822a,1822b.In one example, theaccess regions1834a,1834bare positioned on a side of thepackage1810 opposite the first andsecond filling chambers1822a,1822b.Theaccess regions1834,1834bmay be resealable, and may be configured to provide a sealed interface between a filling device inserted through theaccess regions1834a,1834binto the first andsecond filling chambers1822a,1822bas will be described in further detail below.
• FIGS. 25 a and25billustrate top and bottom perspective views of thedelivery assembly1800.FIG. 25bshows theaccess regions1834a,1834bhaving been penetrated (e.g., pierced) to gain access to the first andsecond filling chambers1822a,1822bas part of filling thecompartment1820.
• FIG. 25cshows the first andsecond filling chambers1822a,1822bcollapsed to remove the contents held in the first andsecond filling chambers1822a,1822bduring filling. Collapsing the first andsecond filling chambers1822a,1822bmay direct the content held therein into thecompartment1820 or into the filling device.
• FIG. 25dshows the first andsecond filling channels1824a,1824bcollapsed to seal closed a flow path between thecompartment1820 and the first andsecond filling chambers1822a,1822b.The fillingchannels1824a,1824bmay be sealed closed using, for example, a heating element. The first andsecond filling channels1824a,1824bafter being sealed may be referred to as first and second sealedchannels1848a,1848b.
• FIG. 25eshows an alternative form of trimming thepackage1810 to remove the collapsed first andsecond filling chambers1822a,1822b.A pair of punchedholes1861a,1861bare formed in thepackage1810 to remove the first andsecond filling chambers1822a,1822b.Other types of trimming are shown with reference to, for example, thepackage10 discussed with reference toFIGS. 1a-1fand thepackage210 shown with reference toFIGS. 5a-5d.The step of trimming may be conducted at a separate location from the filling, collapsing and sealing steps shown with reference toFIGS. 5a-5d.In at least some examples, the trimming step, including punching theholes1861a,1861b,may create contaminants such as dust that may affect sterility of the filling instruments used to fill, collapse and seal thepackage1810.
• FIGS. 26aand 26bshow additional views of thedelivery assembly1800.FIG. 26bshows a cross-sectional view of thecompartment1820, first fillingchamber1822a,first filling channel1824a,access region1834aand a portion of thebody1856 ofpackage1810. The cross-sectional view ofFIG. 26bis included inFIGS. 30a-30eto help illustrate a process or method of filling thepackage1810.
• FIG. 27 shows afilling station1890 of an example filling system. Thefilling station1890 includes aholding cavity1891, acavity vacuum line1892, achamber collapsing member1893, a collapsingmember bore1894, achamber vacuum line1895, aheating member1896, aheating member bore1897, and achannel recess1898. The holdingcavity1891 is sized to receive thecompartment1820 of thepackage1810. The holdingcavity1891 is connected to thecavity vacuum line1892 such that a vacuum applied in thecavity vacuum line1892 holds thecompartment1820 within the holdingcavity1891.
• Thechamber collapsing member1893 is aligned with thefirst filling chamber1822aand moves within the collapsingmember bore1894 toward thefirst filling chamber1822ato collapse thefirst filling chamber1822a.The collapsingmember bore1894 may be connected in flow communication with thechamber vacuum line1895. A vacuum applied in thechamber vacuum line1895 may help hold thefirst filling chamber1822awithin the collapsingmember bore1894. Thechannel recess1898 is sized to receive the first filling channel1824a.Theheating member1896 moves within the heating member bore1897 to contact the first filling channel1824apositioned within thechannel recess1898 to seal closed the first filling channel1824a.
• Thefilling station1890 is shown having a singlechamber collapsing member1893 and asingle heating member1896 that are arranged to interact with thefirst filling chamber1822aand the first filling channel1824a,respectively. Thefilling station1890 typically includes another chamber collapsing member and another heating member that are movable within a chamber member bore and heating member bore, respectively, to interact with thesecond filling chamber1824bandsecond filling channel1824b.The samechamber vacuum line1894 may be in flow communication with both of the collapsing member bores, or aseparate vacuum line1894 may be provided for each collapsing member bore. In some arrangements, a vacuum line may be connected in flow communication with at least one of the heating member bores.
• The collapsingmember bore1894 may have an open end that receives thefirst filling chamber1822a.A shape of the collapsingmember bore1894 may helps shape or maintain a shape of thefirst filling chamber1822aduring filling. The shape of thefirst filling chamber1822aformed by positioning in the collapsingmember bore1984 may be preferred for receiving a particular filling device (e.g., fillingtube1804 shown and described with reference toFIGS. 28aand 28b). A filling chamber having an incorrect or deformed shape may be improperly punctured with the filling device.
• Other filling station embodiments may be operable without using a chamber collapsing member. The content held within the filling chamber of the package may be removed by other means including, for example, suction applied by the fillingtube1804. Alternatively, the content is maintained within the filling chamber of the package after sealing of the filling channel and may be discarded as part of trimming thepackage1810.
• Theheating member1896 may have various constructions and provide sealing in different ways. For example, theheating member1896 may be an impulse sealer operable with a short burst of heat provided by a low energy source using a high conductive heating element.
• FIGS. 28aand 28bshow anexample filling head1802 as part of a filling system comprising thefilling station1890. The fillinghead1802 includes asheath1803 having aflexible skirt1880, anoutlet1881, and aninternal sealing surface1882. The fillinghead1802 also includes a fillingtube1804. The fillingtube1804 may have a pointed tip arranged and configured to penetrate through the access region1834aof thepackage1810 to position the fillingtube1804 within thefirst filling chamber1822a.
• The fillinghead1802 may also include acarrier base1883, adecontamination port1884, abeneficial agent port1885, and a fillingtube support1886. The filling tube support may support the fillingtube1804. Thebeneficial agent port1885 may be arranged in flow communication with the fillingtube1804. Thedecontamination port1884 may be connected in flow communication with an exterior of the fillingtube1804, theoutlet1881 and thesealing surface1882 to flush out the fillinghead1802 prior to connecting with the package1810 (seeFIG. 28a).FIG. 28bshows the fillingtube1804 advanced through theoutlet1881 to a position wherein the fillingtube1804 penetrates into thefirst filling chamber1822a.
• Theskirt1880 of thesheath1803 may flex to permit movement of thecarrier base1883 to advance the fillingtube support1886 and contact with thesealing surface1882, and advance the fillingtube1804 through theoutlet1881. A beneficial agent or a constituent thereof is advanced from thebeneficial agent port1885 and out through the fillingtube1804.
• FIGS. 29aand 29bshow anotherexample filling head1902. The fillinghead1902 includes asheath1903 and fillingtube1904. Thesheath1903 includes askirt1980, anoutlet1981, asealing surface1982, and anexit1905 for the decontamination fluid. The fillinghead1902 also includes acarrier base1983, adecontamination port1984, abeneficial agent port1985, atube support1986, avalve sealing lip1987, and avalve seal membrane1906. Asolenoid body1988 may move asolenoid actuator1989 to move thevalve seal membrane1906 into and out of contact with thevalve sealing lip1987 to control flow of a beneficial agent or constituent thereof via thebeneficial agent port1985 into the fillingtube1904.
• Thesolenoid actuator1989 may help maintain a seal between thevalve seal membrane1906 and thevalve sealing lip1987 during delivery of the decontamination fluid via thedecontamination port1984 around the fillingtube1904 and out of thebeneficial agent exit1905 as shown inFIG. 29a. Thecarrier base1983 is then advanced relative to thesheath1903 to move the fillingtube1904 through theoutlet1981 to advance the fillingtube1904 into thefirst filling chamber1822a.Thesolenoid actuator1989 is then move thevalve seal membrane1906 out of sealing contact with thevalve sealing lip1987 to permit flow of a beneficial agent or constituent thereof from thebeneficial agent port1985 into the fillingtube1904 as shown inFIG. 29b.
• Many other embodiments are possible for filling heads that may be used in conjunction with a filling station for filling various packages, such as those packages described herein with reference to the attached figures. Another example filling head may include one or more vacuum lines used to remove a sample from the package or to remove content held within the filling chamber of the package prior to or after sealing closed the filling channel after filling the compartment. Other types of filling heads may be operable without use of a decontamination fluid and may use different structure besides the sheath shown with reference toFIGS. 28a-29b. Other features are possible for use with the filling head to maintain sterility of the filling head prior to, during, and after interacting with the package and filling station.
• Referring now toFIGS. 30a-30e,an example method of filling thepackage1810 ofdelivery assembly1800, and preparing thedelivery device1812 for use is shown and described.FIG. 30ashows thepackage1810 mounted to thefilling station1890. Thecompartment1820 is positioned within the holdingcavity1891. Thefirst filling chamber1822ais positioned within the collapsingmember bore1894. The first filling channel1824 is aligned within theheating member bore1897. Thecavity vacuum line1892 andchamber vacuum line1895 may apply a vacuum force that holds thepackage1810 in contact with thefilling station1890. The vacuum force applied at thecavity vacuum line1892 andchamber vacuum line1895 may maintain a shape or reshape portions of thecompartment1820 and first fillingchamber1822a.
• The fillinghead1802 may be prepared for interfacing with thepackage1810 by delivering a volume of decontamination fluid via thedecontamination port1884 that passes around the fillingtube1804 and out of theoutlet1881. The fillinghead1802 may be aligned with the access region1834a.A fillingsensor1807 may be mounted to the fillinghead1802 and arranged to align with the first filling channel1824a.The fillingsensor1807 may be operable to determine when thecompartment1820 is filled to capacity. In one example, the fillingsensor1807 determines when at least one of the first filling channel1824aandcompartment1820 no longer has any gas (e.g., air) positioned therein, which indicates that thecompartment1820 is filled completely with contents (e.g., a beneficial agent or a constituent thereof).
• FIG. 30bshows the fillinghead1802 contacting thepackage1810 with the fillingtube1804 advanced through the access region1834aand into thefirst filling chamber1822a.A beneficial agent or a constituent thereof is delivered from thebeneficial agent port1885 through the fillingtube1804, thefirst filling chamber1822a,the first filling channel1824a,and into thecompartment1820. The beneficial agent continues to be delivered until thecompartment1820 is completely filled. As described above, the fillinghead1802 may include another filling tube and features that provide access to thesecond filling chamber1822bconcurrently with accessing thefirst filling chamber1822a.The access viasecond filling chamber1822bmay be used to remove gases from thecompartment1820 while delivering the beneficial agent via thefirst filling chamber1822a.
• After thecompartment1820 is completely filled as confirmed by the fillingsensor1807, the fillingtube1804 may be retracted as shown inFIG. 30cand thechamber collapsing member1893 is advanced to collapse thefirst filling chamber1822a.The content within thefirst filling chamber1822amay be moved through the first filling channel1824ainto thecompartment1820. In other arrangements, the contents held within fillingchamber1822amay be moved to a different location such as, for example, the fillingtube1804.
• FIG. 30dshows the fillingtube1804 further retracted into the original or rest position shown inFIG. 30a. The fillinghead1802 may be removed from contact with thepackage1810 and prepared for filling a different package. Preparation for filling a different package may include, for example, delivering a volume of decontamination fluid as shown inFIG. 30a.
• FIG. 30dalso shows theheating member1896 advanced into contact with the first filling channel1824a.Theheating member1896 may seal closed the first filling channel1824ato seal thecompartment1820. In one example, theheating member1896 is pre-heated before contacting thepackage1810. In other examples, theheating member1896 contacts the package1810 (e.g., the first filling channel1824a) and is then heated.
• FIG. 30eshows thepackage1810 detached from the fillinghead1802 and thefilling station1890. The content ofcompartment1820 may be moved into thedelivery device1812. In one example, the content is drawn into the delivery device by retracting the plunger relative to thebarrel1813. The cap1860 may be removed to permit operation of the plunger.
• The frangible seal1830 (seeFIGS. 25a-25e) may be ruptured or otherwise broken in order to provide fluid communication between thepackage1810 and thedelivery device1812. Thedelivery device1812 as shown inFIG. 30emay be prepared for use with a patient by moving the content ofcompartment1820 into thedelivery device1812 and detaching thepackage1810 from thedelivery device1812 to expose an administration member such as, for example, a needle that is attached to thedelivery device1812 at an end opposite the plunger.
• Prior to loading thedelivery device1812 with the content of compartment1820 (as shown inFIG. 30e) and after sealing the first filling channel1824a(as shown inFIG. 30d), thepackage1810 may be trimmed to remove at least a portion thereof. The trimming step may include, for example, removing the first andsecond filling chambers1822a,1822band at least portions of the first andsecond filling channels1824a,1824b,or associated sealedchannels1848a,1848bas shown inFIG. 25d. The trimming may include punching the punchedholes1861a,1861bas shown inFIG. 25e. The trimming ofpackage1810 may be performed at a different location during manufacturing from a location where the filling system and associated filling, collapsing and sealing steps ofFIGS. 30a-30dare performed.
• FIGS. 31aand 31bshow anexample package1910 in the form of an infusion bag. Thepackage1910 includes first andsecond layers1926,1928 that define at least in part acompartment1920, a plurality of filling chambers1922a-1922d,and a plurality of filling channels1924a-1924dbetween the first andsecond layers1926,1928. Thepackage1910 includes a pair ofoutlet ports1919a,1919bthat are connected in flow communication with thecompartment1920. The filling chambers1922a-1922dand filling channels1924a-1924dmay be used to fill thecompartment1920 with content (e.g., a beneficial agent or a constituent thereof), and theoutlet ports1919a,1919bmay be used to remove the content. In at least some examples, thepackage1910 is resealable after filling thecompartment1920 via the filling chambers1922a-1922dand filling channels1924a-1924dand before removing the content via at least one of theoutlet ports1919a,1919b.
• Theinfusion bag1910 may provide avariable volume compartment1920. Thecompartment1920 may be provided in a sealed state and completely empty (e.g., in a vacuum state). Thecompartment1920 may hold variable amounts of content (e.g., liquid beneficial agent) without needing to concurrently remove gases. Alternatively, thecompartment1920 may include a volume of gas that is removed as the beneficial agent is filled into thecompartment1920.
• The filling chambers1922a-1922dmay be accessed through access regions1934a-1934don the second wall1928 (seeFIG. 31b). Alternatively, the filling chambers1922a-1922dmay be accessed along thefirst wall1928. The filling chambers1922a-1922dmay be deformed (e.g., collapsed) prior to or after filling of thecompartment1920. For example, the filling chambers1922a-1922dmay be collapsed as shown inFIG. 31cfor purposes of rolling or stacking thepackage1910 when storing or shipping thepackage1910 prior to filling. The filling chambers1922a-1922dmay be restored to their original or filling shape (seeFIGS. 31aand 31b) by applying, for example, a vacuum force to the filling chambers1922a-1922dwhen positioning in a filling station (e.g., fillingstation1890 described above).
• FIGS. 32aand 32bshow anotherexample package2010 in the form of an infusion bag. Thepackage2010 includes acompartment2020, a fillingchamber2022, a plurality of filling channels2024a-2024d,first andsecond walls2026,2028, and first andsecond outlet ports2019a,2019b.The fillingchamber2022 may be constructed as an insert that is positioned between the first andsecond walls2026,2028. The fillingchamber2022 may include anaccess region2034 that is exposed outside of the first andsecond walls2026,2028. Theaccess region2034 may include a barrier that provides a fluid-tight seal with a filling device such as a filling tube that pierces the barrier. Other arrangements may include a plurality of fillingchambers2022 as separate inserts that are provided in flow communication with at least one of the filling channels2024a-2024d.
• FIGS. 33aand 33bshow anotherexample package2110 in the form of an infusion bag. Thepackage2110 includes acompartment2120, first and second access inserts2134a,2134bthat define first andsecond filling chambers2122a,2122b,first and second filling channels2124a,2124b,first and second walls2126,2128, and first andsecond outlet ports2119a,2119b.The first and second access inserts2134a,2134bmay be operable between collapsed (seeFIG. 33a) and opened (seeFIG. 33b) positions.Access portions2135a,2135bof the first and second access inserts2134a,2134bprovide access to the first andsecond filling chambers2122a,2122bvia an filling device (e.g., a filling tube) when the first and second access inserts2134a,2134bare in the opened position ofFIG. 33b.
• Thepackage2110 may include amargin portion2121 surrounding at least a portion of the first and second access inserts2134a,2134b.Themargin portion2121 is shown extended or stretched inFIG. 33a. Thepackage2110 may include flexible or elastic materials in themargin portion2121 to facilitate opening and closing the first and second access inserts2134a,2134b.
• FIGS. 34a-34cshow anotherexample access insert2234. Theaccess insert2234 includes anaccess portion2235 through which a filling member accesses afilling chamber2222 defined when theaccess insert2234 moves from a closed position (seeFIGS. 34aand 34b) to an opened position (seeFIGS. 34cand 34d). The fillingchamber2222 may be arranged in flow communication with a compartment of a package via at least one filling channel.
• The access inserts2134a,2134band2234 may provide for a reduced profile package during shipping and storage of the package when the access inserts are in a closed position. The access inserts may be moved into the opened position when filling the package. The filling system used to fill the package carrying the access insert may move the access insert into the open position before attempting to insert a filling device (e.g., filling tube) through the access region of the access insert and into the filling chamber.
• A compression panel may be associated with the packages disclosed herein to facilitate depression of at least one compartment of the cartridge either to urge the rupture of a rupturable barrier, or to urge expression of the dispensable product from the package.
• The arrangements and methods described herein may be applicable for other injectors or dispenser types such as a cartridge or package that includes a retractable needle mechanism, retractable needle connector mechanism, or other needle safety mechanism, or that includes a reusable disabling mechanism or prevention device that is incorporated into the package. The package may be combined with several forms of delivery devices or applicators to facilitate a desired form or use. A compression panel or roller may be incorporated to facilitate an efficient expression of the package content. The delivery device or applicators may include, for example, any one of a medical syringe, staked-needle syringe, safety syringe, retractable needle syringe, auto-disabling syringe, autoinjector, jet injector, intradermal syringe, subcutaneous syringe, intramuscular syringe, infuser, infusion pump, sustained release delivery system, and patch pump. Other applications for the package may be applicable to syringe and jet injector applications, which are provided here by way of example, and the teachings described herein may be applied to other applications such as aseptic filling of micropump reservoirs, intramuscular autoinjectors, and intradermal autoinjectors.
• The applications of the present invention are not limited to the syringe and jet injector applications which are provided here by way of example, and the teachings described herein can be applied to other applications such as aseptic filling of micropump reservoir, intramuscular auto injectors, intradermal auto injectors, etc.

Claims (29)

1.-20. (canceled)

21. A cartridge for use with an injector, comprising:

a first wall that comprises at least a first cavity;

a second wall in sealing engagement with the first wall to define at least a first sealed compartment at least partially defined by the first cavity, wherein the first sealed compartment is adapted to contain a first deliverable substance; and

a fitment to selectively provide fluid communication between the first sealed compartment and a reservoir of the injector via a passageway of the fitment to transfer the first deliverable substance from the first sealed compartment to the reservoir of the injector, wherein the fitment defines at least a portion of an aseptic zone through which the first deliverable substance is transferred between the cartridge and the reservoir.

22. The cartridge ofclaim 21, wherein the fitment is adapted to form a fluid-tight seal with a nozzle of the injector.

23. The cartridge ofclaim 22, wherein the injector is a jet injector and the nozzle of the injector with which the fitment is adapted to engage includes a jet nozzle, and wherein the fitment engages the nozzle to define the aseptic zone through with the first deliverable substance is transferred between the cartridge and the reservoir.

24. The cartridge ofclaim 21, wherein the fitment is attached to an outer side of one of the first wall and the second wall, the one of the first wall and the second wall including a through hole providing the fluid communication between the first sealed compartment and the passageway of the fitment.

25. The cartridge ofclaim 21, wherein the fitment further comprises:

a port area adapted to receive a portion of the injector; and

an aseptic cover protecting the port area when the fitment is not engaged with the injector.

26. The cartridge ofclaim 21, wherein the fitment further comprises:

a port area having conformal elements adapted to conform to structural elements of the injector, wherein the conformal elements are adapted to maintain the aseptic zone when the cartridge is engaged with the injector.

27. The cartridge ofclaim 21, wherein the sealing engagement comprises:

a first frangible seal between the fitment and the first sealed compartment, wherein the cartridge is adapted to provide the first deliverable substance by the first frangible seal being controllably peelable responsive to depression of the first sealed compartment.

28. The cartridge ofclaim 27, wherein adherence of the first wall to the second wall in the first frangible seal is less than adherence of the first wall to the second wall in other portions of the sealing engagement.

29. The cartridge ofclaim 27, further comprising:

a second sealed compartment containing a second deliverable substance, wherein the second deliverable substance is introduced to the second sealed compartment prior to the sealing engagement of the first wall to the second wall.

30. The cartridge ofclaim 29, wherein the sealing engagement further comprises:

a second frangible seal between the first sealed compartment and the second sealed compartment, wherein depressing the first sealed compartment causes peeling of the second frangible seal, the peeling configured to establish fluid communication between the first sealed compartment and the second sealed compartment.

31. The cartridge ofclaim 30, wherein the second deliverable substance includes one or more of a dry constituent, frozen liquid constituent, granulated constituent, micro-pellet constituent, sphere constituent, microsphere constituent, flowable powder constituent, compressed powder constituent, cake constituent, lyophilized cake constituent and a solid constituent of a beneficial agent and the first deliverable substance includes a fluid and wherein the peeling of the second frangible seal causes mixing of the second deliverable substance with the first deliverable substance.

32. The cartridge ofclaim 31, wherein the fluid includes a diluent operable to at least partially dissolve the second deliverable substance when the second frangible seal is peeled.

33. The cartridge ofclaim 21, further comprising:

a drying agent.

34. The cartridge ofclaim 21, further comprising:

a sterile overwrap for storing the cartridge when the cartridge is not engaged with the injector, wherein a drying agent is contained within the sterile overwrap.

35. The cartridge ofclaim 21, wherein one or more of the first and second wall include a drying agent.

36. The cartridge ofclaim 21, wherein one or more of the first wall and the second wall are composed of one or more of a film, a foil, an extruded web, a blown web, a cast web, a multilayer web, a laminated web, a coated web, a web including metallicized layers, a web including at least one metal-oxide layer, a web including a high barrier layer, an aluminum containing layer, alumina, silica, an Olefin Polymer, a Cyclic Olefin Copolymer, a polychlorotrifluoroethylene, and an Ethylene Vinyl Alcohol.

37. The cartridge ofclaim 21, the first wall further comprising at least one optical machine-readable indicium operable to provide information regarding one or more of a content of the cartridge, operating instructions, and warnings.

38. An injector system, comprising:

an injector including:

a tubular body;

a piston disposed in the tubular body, wherein the piston provides a fluid-tight seal with the tubular body defining a reservoir within portions of the tubular body not occupied by the piston; and

a nozzle in fluid communication with the reservoir; and

a cartridge including:

a first wall that comprises at least a first cavity;

a second wall in sealing engagement with the first wall to define at least a first sealed compartment at least partially defined by the first cavity, wherein the first sealed compartment is adapted to contain a first deliverable substance; and

a fitment engageable with the injector to selectively provide fluid communication between the first sealed compartment and a nozzle of the injector via a passageway of the fitment to transfer the first deliverable substance from the first sealed compartment to a reservoir of the injector, wherein the fitment is engageable with the injector to define an aseptic zone through which the first deliverable substance is transferred between the cartridge and the injector.

39. The injector system ofclaim 38, wherein the injector is a jet injector and the nozzle of the injector with which the fitment is adapted to engage includes a jet nozzle.

40. The injector system ofclaim 38, wherein the fitment is adapted to form a fluid-tight seal with the nozzle of the injector.

41. The injector system ofclaim 38, further comprising:

an aseptic cover maintaining sterility of one or more of the nozzle and the fitment when the cartridge is not engaged with the injector.

42. The injector system ofclaim 41, wherein the aseptic cover is one or more of a cap and a sealed foil.

43. The injector system ofclaim 38, wherein the tubular body further comprises:

structural elements adapted to conform to conformal elements of the fitment, wherein the structural elements are adapted to maintain the aseptic zone when the cartridge is engaged with the injector.

44. The injector system ofclaim 38, the piston movable within the tubular body, wherein the piston is movable to configurations including an empty state when the piston is at a most proximal position to the nozzle and a retracted state when the piston is moved distally from the nozzle.

45. The injector system ofclaim 44, wherein the retracted state is a filled state, the filled state resulting from retracting of the piston from the tubular body when the injector is engaged with the cartridge, the retraction causing the first deliverable substance to flow into the reservoir.

46. The injector system ofclaim 38, wherein the one or more of the tubular body and the piston are wrapped in a sterile overwrap.

47. The injector system ofclaim 38, wherein the injector system is assembled in a sterile environment, the injector is engaged with the cartridge in the sterile environment, and the injector system is provided in a non-sterile environment while maintaining the engagement between the injector and the cartridge in the non-sterile environment.

48. The injector system ofclaim 47, wherein the engagement maintains the aseptic zone after the injector system is provided in the non-sterile environment.

Images