EP2723395B1

EP2723395B1 - Fluid sterilant injection sterilization device and method

Info

Publication number: EP2723395B1
Application number: EP12802020.3A
Authority: EP
Inventors: Daniel Py
Original assignee: Individual
Current assignee: Individual
Priority date: 2011-06-21
Filing date: 2012-06-21
Publication date: 2017-08-09
Anticipated expiration: 2032-06-21
Also published as: WO2012177933A1; BR112013033307A2; US20130008137A1; CN108619536A; EP2723395A4; HK1198245A1; CN103813811A; EP2723395A1

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

FIELD OF THE INVENTION

The present invention relates to the sterilization of sealed empty containers, and more particularly, relates to the sterilization of sealed empty containers through the injection of nitric oxide gas or other fluid sterilants into the container.

BACKGROUND INFORMATION

Often, containers are manufactured to hold sensitive products that must remain sterile so as to avoid any bacterial or microbial growth therein. This is frequently the case with medicinal, food, nutritional, ophthalmic and other types of products. These containers must therefore be sterilized prior to being filled with the product. Prior art systems have been created to perform such a task; however, these systems may not always be entirely sterile and may briefly expose the container to non-sterile substances, such as air. On the other hand, some prior art systems may effect a completely sterile environment, but are often unduly expensive to implement. Other prior art systems utilize gamma radiation to sterilize containers. A drawback of this method is that the gamma radiation can damage or breakdown the materials used to create the container, closures of the container or seals of the closures. U.S. Patent No. 3,637,102 , for example, describes a method for sterilizing a sealed empty device which includes the step of introducing a fluid sterilant into an interior chamber of the device. International Patent Application WO 2004/074162 A1 describes a system for aseptic filling of packages with liquid products which includes a source of fluid sterilant in communication with an injection member configured to penetrate a septum of an empty chamber of a device.
It is an object of the present invention to overcome one or more of the drawbacks and/or disadvantages of the prior art.

SUMMARY OF THE INVENTION

In accordance with a first aspect, a method comprises the following steps:

(i) penetrating a penetrable septum of a sealed, empty device with an injection member;
(ii) introducing a fluid sterilant through the injection member and into an interior chamber of the device;
(iii) allowing the fluid sterilant to reside within the chamber a sufficient amount of time to render the chamber at least either substantially sterile or substantially bactericidal;
(iv) penetrating the penetrable septum with an injection or filling member and introducing a product through the injection or filling member and into the sterile or bactericidal chamber; and
(v) withdrawing fluid sterilant from the sealed chamber prior to introducing the product into the chamber; and
(vi) resealing the resulting penetration aperture to hermetically seal the product within the chamber.

In some embodiments, steps (i) and (ii) are performed at a fluid sterilant station, step (iii) is performed at a sterilant residence station, step (iv) is performed at a filling or product injection station, and step (vi) is performed at a resealing station, and, in some embodiments, also a curing station.
In some such embodiments, the withdrawing step includes drawing a vacuum through a device inserted through the penetrable septum. In some embodiments, withdrawal of fluid sterilant is performed at a evacuation or vacuum station. In other embodiments, it is performed at the filling station.
In some embodiments, the device inserted through the penetrable septum is a needle. In some embodiments of the present invention, the fluid sterilant is nitric oxide or another free radical gas.
Some embodiments further comprise sterilizing or decontaminating the penetrable surface of the septum prior to step (iv). Some such embodiments further comprise sterilizing or decontaminating the penetrable surface of the septum prior to step (i). In some embodiments, the sterilizing or decontaminating of the penetrable surface includes applying a fluid sterilant or radiation to the penetrable surface. In some embodiments, the fluid sterilant is vaporized hydrogen peroxide ("VHP") and the radiation is ultraviolet ("UV"), gamma, beta, or e-beam.
Some embodiments further comprise introducing an overpressure of sterile air or other gas during steps (iv) and (vi). Some such embodiments further comprise introducing an overpressure of sterile air or other gas during steps (i) and (ii).
In some embodiments, the resealing step includes applying a liquid sealant to the resulting penetration aperture. In some such embodiments, the resealing step further includes applying radiation or energy to the liquid sealant to cure the liquid sealant from a liquid to a solid phase. In some such embodiments, the radiation is UV radiation, such as high energy, pulsed UV radiation. In other embodiments of the present invention, the septum is resealable by applying radiation or energy thereto, and the resealing step includes applying radiation or energy to the septum at the resulting penetration aperture and thermally resealing the penetration aperture. In further embodiments, the septum is thermally resealable, and the radiation or energy is laser or heat radiation or energy.
In accordance with another aspect, an apparatus comprises:

(i) a device including a sealed empty chamber and a penetrable septum in communication with the chamber; and
(ii) a source of fluid sterilant in communication with an injection member for introducing a fluid sterilant through the injection member and into the chamber of the device, and allowing the fluid sterilant to reside within the chamber a sufficient amount of time to render the chamber either sterile or bactericidal. Thereby, the injection member, filling member or needle is further for withdrawing the fluid sterilant from the chamber.

In some embodiments of the present invention, the apparatus further comprises a source of product to be filled into the chamber and coupled in fluid communication with an injection or filling member for penetrating the penetrable septum with the injection or member and introducing the product through the injection member and into the chamber. Some such embodiments further comprise a resealing station for resealing the resulting penetration aperture to hermetically seal the product within the chamber. In some such embodiments, the resealing station includes a source of liquid sealant for metering the liquid sealant onto the resulting penetration aperture and resealing the septum. In some such embodiments, the resealing station includes a radiation or energy source for transmitting radiation or energy onto the liquid sealant to cure the sealant from a liquid to a solid phase. In other embodiments of the present invention, the resealing station includes a radiation or energy source for applying radiation or energy to the septum at the resulting penetration aperture and resealing the penetration aperture, which is resealable by the radiation or energy, e.g., laser radiation.
Thus,_the present invention is directed to an apparatus comprising:

(i) a device including a sealed empty chamber and a penetrable septum in communication with the chamber; and
(ii) first means for penetrating the penetrable septum and introducing a fluid sterilant through the penetrable septum and into the chamber of the device, and allowing the fluid sterilant to reside within the chamber a sufficient amount of time to render the chamber at least either substantially sterile or substantially bactericidal.

Some embodiments further comprise second means for penetrating the penetrable septum and introducing a product through the penetrable septum and into the chamber. Some embodiments further comprise third means for resealing the resulting penetration aperture. Some embodiments further comprise fourth means for either sterilizing or decontaminating the penetrable surface of the septum prior to penetrating it with either the first means or the second means. In some embodiments, the first means is an injection member and source of fluid sterilant coupled in fluid communication thereto; the second means is an injection or filling member and a source of product coupled in fluid communication thereto; the third means is either a liquid sealant or radiation; and the fourth means is a fluid sterilant or radiation.
In some embodiments, the injection member for the fluid sterilant the device for drawing a vacuum, and/or the injection or filling member for the product may be the same, and the member or device is alternatively connectable to a sterilant source, a vacuum source, and a product source. In some embodiments, one or more of fluid sterilant station or module, the sterilant residence station or module, the evacuation or vacuum station or module, the filling station or module, the resealing station or module, and/or the curing station or module are combined such that more than one of the described processes can be performed at a single station or module.
One advantage of the present invention is that the injected fluid sterilant sterilizes or decontaminates the interiors of the devices and thus obviates the need to use gamma radiation or other prior art sterilization and/or decontamination devices and methods. Yet another advantage is that the devices can be sterilized immediately prior to, and in the same facility, or in the same machine, in which the devices are filled.
Other objects and advantages of the present invention, and/or of the currently preferred embodiments thereof, will become more readily apparent in view of the following detailed description of the currently preferred embodiments and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a sterilization and filling system for sterilizing sealed empty containers, subsequent filling of the sterilized container with a product, and resealing the container; and
FIG. 2 is a schematic illustration showing another sterilization and filling system.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

In FIG. 1, a schematic view of a sterilization system for sterilizing sealed empty containers is shown. The sterilization system includes a plurality of stations, including a fluid sterilant injection station 14, a sterilant residence station 16, a product injection station 18, a resealing station 20, and a curing station 22. A plurality of fan/filter assemblies 24 are mounted in fluid communication with the stations, optionally to provide an over-pressure of sterile air or other gas within each station. A device construction station may be provided prior to the sterilization system to manufacture the devices 10.
In the intact molding station 12 shown in FIG. 2, or the device construction station, the devices 10 are manufactured, whereby, in some embodiments, a snap-ring including a one-way valve is formed by co-molding or over-molding. In embodiments containing it, the valve cover is over-molded to the valve body, and in parallel, a pre-form is injection molded and in turn blow molded to form a pouch. The devices 10 may be constructed in accordance with the device and method of manufacture disclosed in U.S. Patent Application Publication No. 2007/0289884 A1, filed May 18, 2007 , titled "Delivery Device with Separate Medicament and Beverage Chambers Connectable in Fluid Communication When Ready for Use, and Related Method", U.S. Patent Application Publication No. 2010/0094245 A1, filed October 9, 2009 , titled "Co-Extrusion Blow Molding Apparatus and Method, and Sealed Empty Devices", U.S. Patent Application Publication No. 2010/0089946 A1, filed October 9, 2009 , titled "Device with Co-Extruded Body and Flexible Inner Bladder and Related Apparatus and Method," and U.S. Patent Application Publication No. 2011/0084098 A1, filed October 8, 2010 , titled "Device with Co-Molded Closure, One-Way Valve and Variable-Volume Storage Chamber and Method". A device body 26 is also molded in parallel with the closure 28 for the device body 26, e.g., the above-described snap ring/valve cover, and other components. When all components are completed, a robotic machine assembles the snap-ring and valve combination to the pouch to form a sealed empty device 10. The sealed empty device 10 may thus be assembled prior to sterilization and/or filling. When fully assembled, each device 10 is a sealed empty container including a body 26, a closure 28 sealing the opening to the body, and a sealed chamber 30 within the body 26.
After being fully assembled, the device 10 is moved to the fluid sterilant injection station 14. At this station, the penetrable surfaces of the device, e.g., the surfaces of the closure 28, can be sterilized, for example, by applying ultraviolet radiation thereto, or by any other form of sterilization known in the art, such as e-beam, gamma, or beta radiation. In some embodiments, further sterilization of the external and penetrable surfaces is performed. Next, a needle 32 or other injection member is inserted into and penetrates the closure 28. When the needle 32 penetrates the closure 28, such that the needle 32 or needle apertures are is in fluidic communication with the sealed chamber 30 of the body 26, a fluid sterilant, such as nitric oxide gas (NO), is injected through the needle 32 into the interior of the sealed chamber 30. After the sterilant, e.g., NO, is introduced into the chamber 30 the needle 32 can be withdrawn. The fluid sterilant utilized is not limited to NO, but may be any suitable sterilant known in the art including vaporized hydrogen peroxide ("VHP").
It should be further understood that the above-listed applications are not limited to just those elements listed previously, but rather, any needle or injection member, injection station, or station involving the injection of fluid into a device 10 could be provided in accordance with these applications.
Alternatively, the device 10 may be provided in according with the teachings of the following patents and co-pending patent applications: U.S. Patent No. 7,032,631, issued April 25, 2006 , titled "Medicament Vial Having a Heat-sealable Cap, and Apparatus and Method for Filling the Vial," which is a continuation-in-part of similarly titled U.S. Patent No. 6,805,170, issued October 19, 2004 , which is a continuation of U.S. Patent No. 6,684,916, issued February 3, 2004 , which is a divisional of similarly titled U.S. Patent No. 6,604,561, issued August 12, 2003 , U.S. Patent No. 7,100,646, issued September 5, 2006 , titled "Sealed Containers and Methods of Making and Filling Same," which is a continuation-in-part of U.S. Patent No. 6,684,916, issued February 3, 2004 , titled "Medicament Vial Having a Heat-sealable Cap, and Apparatus and Method for Filling the Vial," which is a divisional of similarly titled U.S. Patent No. 6,604,561, issued August 12, 2003 .
For example, the closure 28 may contain or define a penetrable and resealable portion or member that is resealable by the application of radiation or energy thereto. In some such embodiments, the penetrable and resealable portion may be formed of a thermoplastic material that is heat resealable to hermetically seal the needle aperture by applying thermal, heat, or laser radiation or energy to it. In some embodiments, the penetrable and resealable portion is resealable by applying laser at a predetermined wavelength and/or predetermined power thereto. The penetrable and resealable portion defines (i) a predetermined wall thickness in an axial direction thereof, (ii) a predetermined color and opacity that substantially absorbs the laser radiation at the predetermined wavelength and substantially prevents the passage of the radiation through the predetermined wall thickness thereof, and/or (iii) a predetermined color and opacity that causes the laser radiation at the predetermined wavelength and/or power to hermetically seal the needle aperture formed in the therein, e.g., in a predetermined time period and substantially without burning the penetrable and resealable portion (i.e., without creating an irreversible change in molecular structure or chemical properties of the material). In some embodiments, the predetermined time period is approximately 2 seconds, less than or equal to about 1.5 seconds, or less than or equal to about 1 second. In some embodiments, the predetermined wavelength of the laser radiation is about 980 nm, and the predetermined power of each laser is less than about 30 Watts, or less than or equal to about 10 Watts, or within the range of about 8 to about 10 Watts. Also in some of these embodiments, the predetermined color of the material is gray or green, and the predetermined opacity is defined by a gray or green colorant (or pigment) added to the material in an amount within the range of about 0.3% to about 0.6% by weight.
In some embodiments, the penetrable and resealable portion incudes a base or underlying portion and a resealing or resealable portion overlying the base portion. In some such embodiments, the base portion may be substantially infusible in response to the application of radiation or energy to the penetrable and resealable portion. In some embodiments, the thickness of the penetrable and resealable portion and/or the resealable portion substantially prevents sufficient radiation or energy or power thereof, from reaching the base portion. In some embodiments, the base portion is formed of a material that is not resealed by the radiation or energy. In some embodiments, the base portion is vulcanized rubber or a silicone material. In some embodiments, the material is compatible, e.g., inert with, with the substance to be placed in the chamber, e.g., the particular medicament. In some embodiments, the resealable portion is a thermoplastic material. In some embodiments, the resealing portion is a curable material, e.g., in response to the radiation or energy, to seal the penetration and form a substantially gas-tight seal between (a) at least one of the chamber 30 and the base portion, and (b) the ambient atmosphere. In addition, the one or more of the underlying portion and overlying portion may have one or more layers.
However, it should be understood that the penetrable and resealable member may be made of any of numerous different materials which are currently known, or which later become known for performing the functions of the resealable member described herein, such as any of numerous different thermoplastic and/or elastomeric materials, including, for example, low-density polyethylene.
In addition, if desired, a lubricant of a type known to those of ordinary skill in the pertinent art may be added to or included in the penetrable and resealable portion, in order to prevent or otherwise reduce the formation of particles upon penetrating the penetrable and resealable portion with the needle or filling member and/or withdrawing therefrom. In one embodiment, the lubricant is a mineral oil that is added to the styrene block copolymer or other thermoplastic compound in an amount sufficient to prevent, or substantially prevent, the formation of particles upon penetrating same with the needle or other filling member. In another, the lubricant is a silicone, such as the liquid silicone sold by Dow Corning Corporation under the designation "360 Medical Fluid, 350 CST", or a silicone oil, that is added to the styrene block copolymer or other thermoplastic compound in an amount sufficient to prevent, or substantially prevent, the formation of particles upon penetrating same with the needle or other filling member. In one such embodiment, the silicone oil is included in an amount within the range of about 0.4% to about 1% by weight, such as within the range of about 0.4 to about 0.6% by weight, or even within the range of about 0.51 or about 0.5% by weight.
Also in accordance with some embodiments, the closure 28 comprises: (i) a styrene block copolymer within the range of about 80% to about 97% by weight (e.g., 95% by weight); (ii) an olefin, such as ethylene alpha-olefins, polyolefins or olefins, within the range of about 3% to about 20% by weight (e.g., about 5%); and (iii) a pigment or colorant added in an amount sufficient to absorb the laser energy, convert the radiation to heat, and melt the stopper material, e.g., to a depth equal to at least about 1/3 to about ½ of the depth of the needle hole, such as (but not limited to) within a time period of less than about 2 seconds, or less than about 1.5 seconds, or less than about 1 second. In some such embodiments, a lubricant, such as a mineral oil, liquid silicone, or silicone oil as described above, may be added in an amount sufficient to reduce friction forces at the needle interface during needle penetration and/or withdrawal, in turn, substantially prevent particle formation.
In addition, the configurations of the needle, vacuum device, injection or filling members 32, 46, 48 that are penetrating the closure 28 are such that the friction forces created at the needle/material interface, and/or the needle stroke through the closure 28 also can be controlled to further reduce or substantially prevent the formation of particles upon penetrating the stoppers with the needles. In yet further embodiments, the needle, etc. can contain a lubricant or friction-reducing coating on it, at least where the needle interfaces with the material of the closure 28.
In addition to or instead of controlling one or more of the above-mentioned parameters to reduce and/or eliminate the formation of particles (e.g., including the silicone oil or other lubricant in the thermoplastic compound, and controlling the configuration of the needle, the degree of friction at the needle/stopper interface, and/or the needle stroke through the stopper), each of which can be used alone or in any desired combination, the differential elongation of the components of the penetrable and resealable portion is selected to reduce and/or eliminate the formation of particles.
In accordance with some such embodiments, the penetrable and resealable portion can comprise a first material having a first elongation, and a second material having a second elongation that is different, e.g., lesser than, the first elongation. In one such embodiment, the first material comprises a first thermoplastic material within the range of about 80% to about 97% be weight and defining a first elongation, and the second material comprises a second thermoplastic material within the range of about 3% to about 20% by weight and defining a second elongation less than the elongation of the first material. In some such embodiments, a pigment or colorant added in an amount sufficient to absorb laser energy, convert the radiation to heat, and reseal the stopper material, for example, to a depth equal to at least about 1/3 to about ½ of the depth of the needle hole, such as (but not limited to) within a time period of less than about 2 seconds, less than about 1.5 seconds, or less than about 1 second. The penetrable and resealable portion can optionally include a lubricant, such as a mineral oil, liquid silicone, or silicone oil as described above, added in an amount sufficient to substantially reduce friction forces at the needle/stopper interface during needle penetration of the stopper to, in turn, substantially prevent particle formation.
In some embodiments, the penetrable and resealable portion is made of a material that itself has sufficient lubricity or otherwise mitigates friction between the material and the needle, etc., or already contains lubricants, that additional lubricant need not be added and/or the above-described needles, etc. need not be used to reduce or prevent particle formation.
In some embodiments, the closure 28 is formed of a suitably resilient and elastic material that can at least substantially reform to its original shape and thus at least substantially close any holes or breaches at the resulting needle penetration site after the needle is withdrawn, and therefore substantially prevent the injected fluid sterilant from escaping out of the chamber. A robotic machine (not shown), such as a pick and place machine, then transfers the fluid sterilant filled device 10 to the sterilant residence station 16. The sterilant filled device 10 remains in the sterilant residence station 16 for a predetermined residence time that is required to render the interior of the device 10 exposed to the fluid sterilant bactericidal or sterile.
In another embodiment, the sterilant residence station 16 may alternatively be a gas sterilization unit 34. As illustrated in FIG. 2, the gas sterilization unit 34 includes a conveyor 36 for transporting the sterilant filled devices 10. The sterilant filled devices 10 are placed on the conveyor 36 by a robotic machine 38 and transported along a circuitous route, allowing the sterilant fluid to sterilize the interior of the devices 10 as they travel the route. The length of the route and the speed of transport of the devices 10 through the gas sterilization unit 34 are correlated such that the time of transport is at least equal to a predetermined residence time required to render the interior of the devices 10 exposed to the fluid sterilant bactericidal or sterile.
Nitric oxide gas is a small module, naturally produced, hydrophobic, free-radical gas. NO exhibits broad reactivity and rapid diffusive properties through biological entities. To this end, NO is naturally produced in the human body as a part of the body's immune defense. NO has been shown to be particularly antimicrobial in nature, directly inhibits the growth of bacteria, and also functions as a killer molecule within activated immune cells. It has been demonstrated that NO gas inhibits and prevents the growth of various microbial pathogens when presented in sufficient quantities and for a sufficient amount of time. Accordingly, the injected NO sterilizes the interior surfaces of the container when left in the chamber for a period of time sufficient to achieve sterilization as the device 10 is transported through the sterilant residence station 16 or the gas sterilization unit 34. As may be recognized by those of ordinary skill in the pertinent art based on the teachings herein, any of numerous other types of fluid sterilants, including any of numerous different types of free-radical gases, that are currently known, or that later become known, equally may be employed.
When the device 10 exits the sterilant residence station 16 the interior of the device is sterile and therefore the device is ready for sterile filling at the product injection station 18, or filling module. A robotic machine, e.g., the robotic machine 40 of FIG. 2, may transfer the device 10 from the sterilant residence station 16, or the gas sterilization unit 34, to a conveyor 42 of the product injection station 18, or the intact filling station 44. In the product injection station 18, the needle penetrable surfaces of the device, e.g., the surfaces of the closure 28, can be sterilized, if desired or needed for example, by applying high intensity ultraviolet ("UV") radiation thereto, or by any other form of sterilization known in the art such as e-beam, gamma or beta radiation. Then, a needle 46 or vacuum device penetrates the closure 28, or septum, either at the same site as the sterilant injection or at a different site, and a vacuum is drawn on the needle to withdraw the fluid sterilant, e.g., NO, from the bactericidal or sterile interior of the device 10. This evacuation may also be produced by a vacuum conduit formed in the needle or on the outer perimeter of the needle.
A filling needle 46 or filling or injection member is then inserted through the closure 28, or septum, either at the same site as the prior needle insertions or at a different site, and aseptically or in a sterile manner fills a desired product through the needle 46 and into the sterile chamber 30.
In further embodiments, the needle 48 may be a "double lumen" or multiple lumen needle, as is known, and described in U.S. Patent No. 6,604,561 , which has a first fluid passageway or conduit for injecting the product into the chamber 30, and a second fluid passageway or conduit for drawing or allowing the fluid sterilant out of the chamber 30 during filling, e.g., via displacement of the sterilant by the filled product or by vacuum, e.g., connecting the second fluid passageway to a vacuum source.
Further, in some embodiments the operations of evacuating the fluid sterilant and filling the device 10 are performed under an over pressure of sterile air or other gas, e.g., nitrogen or an inert gas, to help maintain sterility.
After filling the product into the chamber 30, the device 10 is moved into the resealing station 20 to reseal the resulting penetration aperture(s). In the embodiment shown in Fig. 1, while in the resealing station 20, a metered amount of liquid sealant 50, e.g., a silicone sealant, is applied to the resulting needle penetration aperture(s) in the closure 28 to bond to the closure 28, or septum, and hermetically seal the closure 28. The device 10 is then moved into a curing station 22 where a pulsed ultraviolet light source 52 emits pulsed ultraviolet radiation onto the liquid sealant 50 to cure the sealant, causing it to transition from a liquid phase to a solid phase and, in turn, hermetically seal the underlying needle penetration aperture(s). This process is described in further detail in the previously referenced patent applications.
In alternative embodiments, the resulting penetration aperture(s) can be laser resealed as described above and in accordance with the teachings of the following patents and co-pending patent applications: U.S. Patent No. 7,032,631, issued April 25, 2006 , titled "Medicament Vial Having a Heat-sealable Cap, and Apparatus and Method for Filling the Vial," which is a continuation-in-part of similarly titled U.S. Patent No. 6,805,170, issued October 19, 2004 , which is a continuation of U.S. Patent No. 6,684,916, issued February 3, 2004 , which is a divisional of similarly titled U.S. Patent No. 6,604,561, issued August 12, 2003 ; U.S. Patent No. 7,100,646, issued September 5, 2006 , titled "Sealed Containers and Methods of Making and Filling Same," which is a continuation-in-part of U.S. Patent No. 6,684,916, issued February 3, 2004 , titled "Medicament Vial Having a Heat-sealable Cap, and Apparatus and Method for Filling the Vial," which is a divisional of similarly titled U.S. Patent No. 6,604,561, issued August 12, 2003 .
In other embodiments, such as, by way of example only, as described in U.S. Patent No. 7,100,646 , the penetration aperture can be resealed by placing a cover or covering portion over the aperture, and thereby forming a substantially gas-tight seal between (a) at least one of the chamber 30 and the closure 28, and (b) the ambient atmosphere. The cover or covering portion can alternatively or additionally help provide a moisture vapor transmission (MVT) barrier therebetween. In some embodiments, the cover or covering portion is penetrable, so that, to withdraw the substance from the chamber 30 after resealing, a needle or other withdrawing device can be inserted through the cover and into the chamber 30 without removing the cover or the closure 28, reducing exposure of the substance in the chamber 30 to the ambient atmosphere.
At this point, the devices 10 may be transferred by a robotic machine, e.g., the robotic machine 54 of FIG. 2, to a boxing and labeling conveyor 56 of a boxing and labeling station 58 where the devices 10 are prepared for distribution.
In some embodiments, the conveyors utilized may be "Montrac" conveyors manufactured by the Swiss company Montech AG. For example, for the embodiment of FIG. 2, the gas sterilization conveyor 36, which travels through the gas sterilization unit 34, the filling conveyor 42, and the boxing and labeling conveyor 56 may each employ a Montrac conveyor. Each conveyor is configured in a manner known to those of ordinary skill in the pertinent art to transport the devices 10 along the respective conveyor.
In another embodiment, each sterilization system may include a plurality of stations per module. For example, a sterilization system may include 3 stations per module. In this exemplary embodiment, there are 3 ultraviolet sterilization stations (which may include ultraviolet sterilization, fluid sterilant injection, and sterilant residence), 3 NO evacuation/vacuum stations, 3 product filling stations, 3 liquid sealant stations, and 3 ultraviolet curing stations per module. The number of stations per module may be increased or decreased to match a desired throughput of the system.
In another embodiment of the present invention, each sterilization system may include only one station per module. In one such exemplary embodiment, the module may include one ultraviolet sterilization station, one fluid sterilant injection station (which may include sterilant residence), and a laser resealing station. In this exemplary embodiment, there is no need to evacuate the fluid sterilant because it has no adverse reaction with the product fill.
In yet other embodiments, in accordance with the teachings of U.S. Patent No. 7,096,896 , one or more of the above stations or modules and/or their functions, can be combined, such that more than one function is performed at one station or location. In such embodiments, no conveyor or robotic device is needed to move the device 10 between "combined" stations.
In yet further embodiments, the needles 32, 46, 48 maybe combined, such that one needle may be used to perform more than one of the sterilant injection, vacuum, and filing functions. For example, the closure 28 may be penetrated by the needle 32 and the sterilant injected, and then the sterilant source may be disconnected from the needle, e.g., by valves or other methods, and the needle can then be connected to a vacuum source, e.g., by valves or other methods. In yet other embodiments, the closure 28 is penetrated by the needle 46 and the vacuum applied, the vacuum source disconnected from the needle, e.g., by valves or other methods, and the needle connected to the product source, e.g., by valves or other methods, to fill the chamber 30. In additional embodiments, only one needle may be used, alternately connected sterilant, vacuum, and product. In some such embodiments, a multiple lumen member (having two or more fluid passageways) may be used, with different lumens connected or connectable to the different sources. In such embodiments, the amount of times the closure 28 needs to be penetrated (and withdrawn from) is reduced, reducing overall processing time, reducing the number of penetrations in the closure 28, and perhaps consequent resealing time (fewer holes to seal), increasing sealing integrity of the closure, reducing or eliminating the need to re-sterilize the exposed surfaces of the closure 28, and reducing potential contamination of the chamber 30 and/or product therein.
As should be recognized by those of ordinary skill in the pertinent art based on the teachings herein, numerous changes and modifications may be made to the above-described and other embodiments of the present invention without departing from its scope as defined in the appended claims. Further, any of the above described features may be used and combined in any manner with each other. Thus, the invention is not limited to the specifically described embodiments and combinations, but can include or exclude any feature or combinations of features. Accordingly, this detailed description of embodiments is to be taken in an illustrative, as opposed to a limiting, sense.

Claims

A method comprising the following steps:
(i) penetrating a penetrable septum (28) of a sealed empty device (10) having a sealed interior chamber (30) within with an injection member (32, 46, 48);

(ii) introducing a fluid sterilant through the injection member (32, 46, 48) and into the interior chamber (30) of the device (10);

(iii) allowing the fluid sterilant to reside within the chamber (30) a sufficient amount of time to render the chamber (30) either sterile or bactericidal; and

(iv) introducing a product through the septum (28) and into the sterile or bactericidal chamber (30);
characterized in that
the interior chamber (30) remains sealed after said penetrating step and during said introducing step (iv); and the method further comprises
(v) resealing the resulting penetration aperture to hermetically seal the product within the chamber (30).
A method as defined in claim 1, further comprising withdrawing fluid sterilant from the chamber (30) prior to introducing the product into the chamber (30).
A method as defined in claim 2, wherein the fluid sterilant is withdrawn through the same injection member (32, 46, 48) through which the fluid sterilant is introduced into the interior chamber (30).
A method as defined in any of claims 1 to 3, wherein the withdrawing step includes drawing a vacuum through a device inserted through the penetrable septum (28), and preferably, the device is defined by the injection member (32, 46, 48), and more preferably, the device is a needle.
A method as defined in claim 4, wherein the injection member (32, 46, 48) is alternately connected to the sterilant and a vacuum source and/or a multiple lumen member connected or connectable to the sterilant and a vacuum source.
A method as defined in any of claims 1 to 4, wherein the step of introducing the product includes introducing the product through the same injection member (32, 46, 48) through which the fluid sterilant is introduced into the interior chamber (30), and, preferably, the injection member is alternately connected to the sterilant and the product and/or is a multiple lumen member connected or connectable to the sterilant and the product.
A method as defined in any of the preceding claims, wherein the fluid sterilant is nitric oxide.
A method as defined in any of the preceding claims, further comprising sterilizing or decontaminating a penetrable surface of the septum (28) prior to at least one of steps (i) and (iv), preferably including applying a fluid sterilant or radiation to the penetrable surface, and more preferably, the fluid sterilant is VHP and the radiation is UV.
A method as defined in any of the preceding claims, further comprising introducing an overpressure of sterile air or other gas during at least one of steps (i), (ii), (iv) and (v).
A method as defined in any of claims 1 to 9, wherein the resealing step includes applying a liquid sealant to the resulting penetration aperture.
A method as defined in claim 10, wherein the resealing step further includes transitioning the liquid sealant from a liquid to a solid phase.
A method as defined in claim 10, wherein the resealing step further includes applying radiation or energy to the liquid sealant to cure the liquid sealant from a liquid to a solid phase, and preferably, the radiation or energy is UV.
A method as defined in any of claims 1 to 9, wherein the resealing step includes applying radiation or energy to the septum (28) at the resulting penetration aperture and thermally resealing the penetration aperture.
An apparatus comprising the combination of:
a device (10) including a sealed empty chamber (30) and a penetrable septum (28) in communication with the chamber (30); and

a source of fluid sterilant in communication with an injection member, filling member or needle (32, 46, 48) for penetrating the septum (28) and introducing a fluid sterilant through the injection member, filling member or needle (32, 46, 48) and into the chamber (30) of the device (10), and allowing the fluid sterilant to reside within the chamber (30) a sufficient amount of time to render the chamber (30) either sterile or bactericidal;

characterized in that

the septum (28), interior chamber (30) and the injection member, filling member or needle (32, 46, 48) are adapted such that the interior chamber (30) remains sealed after penetrating the septum and while introducing the fluid sterilant into the chamber (30); and

the apparatus comprises a resealing station (20) for resealing the resulting penetration aperture to hermetically seal the product within the chamber (30).
An apparatus as defined in claim 14, wherein the injection member, filling member or needle (32, 46, 48) is further for withdrawing the fluid sterilant from the chamber (30).
An apparatus as defined in claim 14 or 15, further comprising a vacuum source, wherein the injection member (32, 46, 48) is adapted to be alternately connected to the source of fluid sterilant and the vacuum source and/or the injection member (32, 46, 48) is a multiple lumen member connected or connectable to the sterilant and the vacuum source.
An apparatus as defined in any of claims 14 to 16, further comprising:
a source of product to be filled into the chamber and coupled in fluid communication with the injection member, needle or filling member (32, 46, 48) for penetrating the penetrable septum therewith, for introducing the product therethrough and into the sterile or bactericidal chamber (30).
An apparatus as defined in claim 17, wherein the injection member, needle or filling member (32, 46, 48) is adapted to be alternately connected to the source of fluid sterilant and the source of product and/or the injection member, needle or filling member (32, 46, 48) is a multiple lumen member adapted to be connected to the source of fluid sterilant and the source of product.
An apparatus as defined in claim 17 or 18, further including a source of liquid sealant for dispensing the liquid sealant onto the resulting penetration aperture and resealing the septum (28).
An apparatus as defined in claim 19, further including a radiation or energy source for transmitting radiation or energy onto the liquid sealant to cure the sealant from a liquid to a solid phase.
An apparatus as defined in claim 14, wherein the resealing station (20) includes a radiation or energy source for applying radiation or energy to the septum (28) at the resulting penetration aperture and thermally resealing the penetration aperture.