Micro-environment method and apparatus for sterile manufacturing of medical or pharmaceutical products

Abstract

The disclosure relates to systems and methods for electron-beam (EB)-based sterilization, and more particularly, to an improved solution for sterilizing medical products or packaged pharmaceuticals in a controlled microenvironment integrating packaging and sterilization.

Description

MICRO-ENVIRONMENT METHOD AND APPARATUS FOR STERILE MANUFACTURING OF MEDICAL OR PHARMACEUTICAL PRODUCTSBACKGROUND

[0001] The disclosure is directed to systems and methods for electron-beam (EB)-based sterilization, and more particularly, to an improved solution for sterilizing medical products or packaged pharmaceuticals in a controlled microenvironment integrating packaging and sterilization.

[0002] Sterilization of medical instruments and, for example, saline IV bags using ionizing radiation is a highly effective and widely adopted method in healthcare and pharmaceutical industries. Ionizing radiation sterilization primarily employs gamma rays, electron beams (E-beams), or X-rays to achieve sterility by disrupting the DNA of microorganisms, rendering them inactive. This sterilization method is particularly advantageous for single-use medical devices, pharmaceuticals, and pre-packaged products because it can sterilize without opening the packaging, ensuring sterility during storage and transport.

[0003] Gamma radiation, typically sourced from Cobalt-60, is the most commonly used ionizing radiation method. It offers deep penetration and uniform dose distribution, making it suitable for dense and / or irregularly shaped products and instruments or devices. However, the process requires extensive shielding due to the high energy of gamma rays, necessitating specialized facilities with robust safety measures.

[0004] Electron beam sterilization, on the other hand, uses high-energy electrons generated by accelerators. While faster than gamma radiation and does not rely on radioactive isotopes, its penetration depth is relatively limited, making it less suitable for dense materials. X-ray sterilization combines some advantages of both methods, offering deeper penetration than E-beams but requiring less shielding than gamma radiation.

[0005] Facilities utilizing ionizing radiation for sterilization must meet stringent regulatory and safety standards. These include shielding to protect workers from radiation exposure, dosimetric validation to ensure consistent application of the appropriate dose, andadherence to international standards such as ISO 11137 for healthcare product sterilization. Additionally, facilities must maintain precise control over parameters like dose range and load configuration to ensure efficacy without compromising product integrity.

[0006] Despite its effectiveness, ionizing radiation sterilization faces several challenges. One significant issue is the potential for material degradation. Gamma rays and E-beams can induce chemical changes in certain polymers and biologies, such as polyethylene or tissue grafts, potentially altering their mechanical properties or clinical performance, for example, by redistribution of plasticizers in polymers, leading to accelerated aging of blister packs and the like.

[0007] Likewise, gamma radiation can generate free radicals that degrade polymers like polypropylene or polycarbonate, limiting their clinical use, mainly in certain medical devices such as hypodermics, secure fluid transfer systems and the like. To mitigate these effects, manufacturers may incorporate stabilizers or adjust dose levels during sterilization.

[0008] Another challenge is cost. The infrastructure required for ionizing radiation facilities is expensive to build and maintain, furthermore, the reliance on Cobalt-60 as a gamma source raises concerns about supply chain stability and disposal of radioactive waste (as does Cesium 137). These factors make ionizing radiation more suitable for large-scale industrial applications rather than small healthcare facilities.

[0009] In the case of saline IV bags specifically, ionizing radiation offers a reliable method to achieve sterility without compromisingthe contents' integrity. Gamma orX-ray sterilization can penetrate the saline solution and packaging effectively. However, care must be taken to avoid radiolysis of the saline solution, which could produce impurities or alter its chemical composition. Moist heat sterilization may sometimes be preferred for saline bags due to its lower risk of introducing radiolytic impurities.

[0010] Addressing these and other issues are provided in the systems and methods for improved solution for sterilizing medical products or packaged pharmaceuticals in a controlled microenvironment integrating packaging and sterilization, will become apparent from the following detailed description when read in conjunction with the figures and examples, which are exemplary, not limiting.SUMMARY

[0011] Disclosed in various exemplary implementations, are improved solutions for sterilizing medical products or packaged pharmaceuticals in a controlled microenvironment integrating packaging and sterilization.

[0012] In an exemplary implementation, provided herein is an integrated sterilizationpackaging system comprising: a point-of-use (POU) sterilization module; an ambiently isolated packaging microenvironment; and optionally an irradiation isolation module.

[0013] In another exemplary implementation, provided herein is a method of sterilizing a packaged medical product, implemented in a system comprising: a point-of-use (POU) sterilization module havinga product vesseltransferstage, an ambiently isolated packaging microenvironment having a material handling module in communication with the product vessel transfer stage, and optionally an irradiation isolation module, wherein the method comprises the steps of: Irradiating a product vessel in the POU sterilization module;Transferringthe product vessel into the ambiently isolated packaging microenvironment; filling the product vessel with the product; and removing the product from the ambiently isolated packaging microenvironment.

[0014] These and other features of systems and methods for improved solution for sterilizing medical products or packaged pharmaceuticals in a controlled microenvironment integrating packaging and sterilization, will become apparent from the following detailed description when read in conjunction with the figures and examples, which are exemplary, not limitingBRIEF DESCRIPTION OF THE DRAWINGS

[0015] For a better understanding of the systems and methods for improved solution for sterilizing medical products or packaged pharmaceuticals in a controlled microenvironment integrating packaging and sterilization, reference is made to the accompanying examples and figures, in which:

[0016] FIG. 1 , illustrates a schematic showing an exemplary implementation of macro-to-micro environment process;

[0017] FIG. 2, is a schematic of an exemplary implementation of the integrated fill system illustrated in FIG.1

[0018] FIG. 3, is a schematic illustrating the micro-environment internal to the fill system; and

[0019] FIG. 4 is another exemplary implementation of an open vessels in an integrated irradiation and fill system.DETAILED DESCRIPTION

[0020] Provided herein are exemplary implementations of systems and methods for improved solutions for sterilizing medical products or packaged pharmaceuticals in a controlled microenvironment integrating packaging and sterilization.

[0021] Accordingly, and in exemplary implementations as disclosed in FIG.s 1-4, provided herein is an integrated sterilization-packaging system 1 comprising: a point-of-use (POU) sterilization module 110; an ambiently isolated packaging microenvironment 20; and optionally an irradiation isolation module 300 (see e.g., FIG. 2).

[0022] The method and systems are configured to provide a micro-environment approach to improve the quality, cost, and cycle time of assembling sterile products in the medical and pharmaceutical industries. As indicated, current methods typically employ macro methods by creating larger enclosures to protect the product relative to a clean environment with the potential for bio-burden impact on such products. Such bio-burdens impact the safety of human or animal products, such as for example, injectables, transfused, or topical formulations.

[0023] A point-of-use electron beam (E-beam) sterilization module refers in an exemplary implementation, to a system operable to sterilize medical devices, pharmaceuticals, and other healthcare products directly at the site of manufacturing, distribution or use. The module comprises several components, each having a specific role in ensuring effective and efficient sterilization. These components can include an electron gun, an electron accelerator, magnetic optical system, material-handling system, radiation shielding, and (typically computerized) control systems. Together, they create a controlledenvironment where high-energy electrons are generated, directed, and applied to achieve sterility.

[0024] Accordingly, and in another exemplary implementation, the POU sterilization module used in the systems and methods disclosed, can comprise: a shielded processing chamber having, an entry and an exit; an E-Beam generator, operably coupled to the shielded processing chamber; and the product vessel transfer stage, operable to convey the product vessel sought to be sterilized through the shielded processing chamber, wherein the E-Beam generator is operable to adjust irradiation between about 0.1 MeV and about 40.0 MeV.Therefore, the E-Beam generator has the capability to vary electron beam energy levels within a range having approximate lower and upper boundaries of 0.1 million electron volts and 40.0 million electron volts, respectively, "operable to adjust" means that the generator is fully functional, calibrated, and capable of changing energy output to accommodate different product vessel densities, surface contours, and material compositions. The generator need not access the entire range simultaneously but must be capable of adjustment within the specified boundaries, while the term "about" reflects reasonable tolerances, measurement error, and rounding inherent in radiation equipment, permitting minor deviations from the exact numerical endpoints.

[0025] For example, the core of the E-beam sterilization module is an electron gun, operable to generate the primary beam of electrons. This component can consist of a cathode, grid, and anode, working together to produce and accelerate electrons to high velocities. The electrons are then passed through an accelerator, which boosts their energy levels to between 0.8 MeV and 40 MeV — sufficient to penetrate the material being sterilized.

[0026] The energy level can be adjusted depending on the density, surface contour, and composition of the product sought to be sterilized - to ensure uniform dose distribution without damaging sensitive materials. Once the electrons are accelerated, they are guided by a magnetic optical system, which focuses and deflects the electron beam to ensure precise targeting of the product. This system creates a "curtain" of high-energy electrons that can be scanned, or rastered across the product surface or directed into its packaging. The ability tocontrol beam parameters such as intensity and direction is beneficial for achieving consistent sterilization while minimizing material degradation.

[0027] The material-handling system, orthe product vessel transfer stage can typically comprise conveyors or automated carriers that transport products through the sterilization chamber at controlled speeds, ensuringthat each product receives the correct radiation dose as it passes through the electron beam. In some configurations, products (e.g., those having complex surface topology), are irradiated from multiple angles or sides to achieve uniform dose distribution.

[0028] In certain exemplary implementations, the handling system can also be customized to accommodate various product shapes and sizes, making it versatile for different applications.

[0029] To ensure safety during operation, the module is enclosed within robust radiation shielding made from certain materials used to prevents any ionizing radiation from escaping into the surrounding environment, protecting personnel, equipment and the ambiently isolated filing module. In certain implementations of the systems and methods disclosed, self-contained modules include integrated shielding, allowingthem to be installed in standard facilities without requiring extensive structural modifications.

[0030] Furthermore, advanced control systems oversee all aspects of the sterilization and filling / packaging unit operations. These command-and-control (C3[critical command-and -control]) systems monitor key parameters such as beam energy, conveyor speed, and dose delivery in real time. Moreover, and in yet another exemplary implementation, these C3systems are operable to control the ambiently isolated microenvironment where the packaging processes take place. The C3systems (which can be remote, or server-based) also archive historical data for validation purposes and ensure compliance with regulatory standards such as ISO 11137 for healthcare product sterilization. The C3systems used in the systems and methods provided further comprise graphic user interfaces and automated diagnostics to simplify operation and maintenance. In addition to these components, auxiliary features may enhance performance or address specific needs. For example, dosimeters are used to measure radiation doses during operation, ensuringthat products receive adequateexposure without exceeding safe thresholds. Some modules can also include ozone management systems to mitigate ozone generation during high-energy electron interactions with air.

[0031] In certain exemplary implementations, housing configuration of the E-beam sterilization module depend on its size and intended use (e.g., wet products vs. medical devices). At a minimum, facilities provide adequate space forthe equipment and its shielding enclosure. Likewise, reliable power supply is included for operating the accelerator and associated electronics. Environmental controls such as temperature and humidity regulation may also be included to maintain optimal operating conditions.

[0032] In certain exemplary implementations, the ambiently isolated packaging microenvironment comprises: an ambiently isolated chamber 20 having an entry 510 and an exit 520; a product filling module 70; a product sealing module 80; a material handling module 530, in communication with the product vessel transfer stage, the material handling module 530 operable to transfer the product vessel 10 from the ambiently isolated chamber entry 510, to the product filling module 70 and the product sealing module 80 and through the ambiently isolated chamber’s exit 520.

[0033] As illustrated e.g., in FIG.3, the ambiently isolated packaging microenvironment 200 can be further enhanced with systems to input filtered ambient air 500 or inert gases such as nitrogen or argon to maintain sterility and reduce oxidative reactions during packaging. Additional features include an electrostatic emitter 550 to neutralize static charges that could attract contaminants and a source of electromagnetic radiation 560 emitting actinic UVC wavelengths to further sanitize surfaces before sealing. In an alternative configuration multiple product vessels or a single product vessel can be accommodated. Following entry into the micro-environment, three steps are performed, such as opening (unsealing) the irradiated vessel, filling the vessel, and then resealing for maintaining sterility integrity. Post these three steps the vessel will exit the micro-environment. The number of open (unsealing)60 / fill 70 / seal 80 modules in the microenvironment is optimized in an example, based on the factory POU needs, as well as in combination with optimizingthe rate of irradiation for effective sterility. The latter which can be accomplished by adjusting both theirradiation energy and the transport speed. As indicated, irradiation can be using either a high-energy electron beam or x-rays. In an exemplary implementation, eBeam energies range from about 0.5 MeV to about 10 MeV, for example, from about 0.8 MeV to about 6 MeV.

[0034] The optional irradiation isolation module 300 can be used in certain implementations, to ensure safety by attenuating radiation leakage from the E-Beam generator or other sources. This module 300 may include at least one layer composed of high-Z materials such as lead or tungsten to absorb high-energy radiation and another layer made of low-Z materials like polyethylene or boron-containing compounds to scatter and dissipate secondary radiation. Alternatively, or additionally, a filtered gas curtain can be employed within the ambiently isolated chamber to contain radiation while allowing material transfer.

[0035] In an exemplary implementation (see e.g., FIG.s. 2-4), the system also supports advanced functionalities such as unsealing product vessels using an unsealing module 60, before filling, and further, the abilityfor repositioning product vessels 320 for optimal processing, and resealingthem post-filling 323’. These operations are managed by the material handling module with precision actuators 311, 311’ or robotic arms to ensure minimal human intervention and maximum sterility, without compromising product flow through the process.

[0036] In certain exemplary implementations, the methods provided are implemented with the systems disclosed. Accordingly, provided herein is a method of sterilizing a packaged medical product, implemented in a system comprising: a point-of-use (POU) sterilization module having a product vessel transfer stage, an ambiently isolated packaging microenvironment having a material handling module in communication with the product vessel transfer stage, and optionally an irradiation isolation module, wherein the method comprises the steps of: Irradiating a product vessel in the POU sterilization module;Transferringthe product vessel into the ambiently isolated packaging microenvironment; Fillingthe product vessel with the product; and Removingthe productfrom the ambiently isolated packaging microenvironment.

[0037] Accordingly, and in another exemplary implementation, the process would be to irradiate a product vessel 10 consisting of given materials for the retention of liquids, solids, orcompounding before a fill. The product vessel would be empty and have sealed nozzles, entry points, etc. to create the micro-environment. The vessel is irradiated and consequently sterilized. Once the vessel is irradiated, none of the openingswill be compromised to maintain sterility until the next manufacturing step of filling.

[0038] Next is the entry of the vessel into a fill machine, whereby the product vessel will pass from the irradiation unit into the fill unit via a microenvironment isolated from the entire machine for the management of any contaminants. This microenvironment can be isolated with entry doors (see e.g., entry 520), and inert or air curtain, electrostatic emitters to allow particles to agglomerate, sink and be flushed out of the environment. In addition, UVC can be included to reduce the bioburden of surfaces of the machine or vessel during entry.

[0039] Once the vessel is secured into the micro-environment of the filling machine a nozzle cut, pull cap, turn cap, or septum for injection of materials, or other robotic system can be used to fill the fluid or solid material. The fill area is configured in an exemplary implementation, to accommodate a single product vessel in orderto maintain the integrity of sterility. Post-fill, the product vessel will be resealed 1000 (see e.g., FIG.1 , using sealing module 80 (see e.g., FIG. 3) and moved out of the ambiently isolated microenvironment for subsequent processes, such as, for example, labeling, overwrap, or QA / QC inspections.

[0040] In an exemplary implementation, the fill microenvironment and the sterilization module are fully integrated into a single system where the product vessel is transported between the two processing modules within a common sterile microenvironment. In other words, a single integrated processing unit of sterilization and filling (or packaging).Furthermore, the transfer mechanism is configured such that the distance between the filling device and the vessel entry port is constant regardless of the length and width of the product vessel.DEFINITIONS:

[0041] The term “point-of-use (POU) sterilization module” refers to a sterilization system positioned at or integrated with the location where packaging and filling operations occur, enabling sterilization directly at the manufacturing site rather than at a separate, centralized sterilization facility. The term intends to distinguish localized sterilizationequipment that is proximate to and coordinated with the packaging microenvironment from traditional off-site batch sterilization facilities. The module performs electron beam sterilization of product vessels immediately before they enterthe filling process. "Point-of-use" does not require sterilization at the ultimate clinical use site but rather refers to sterilization at the point of manufacturing use.

[0042] As used herein, the term "ambiently isolated packaging microenvironment" refers to a localized, controlled chamberthat is separated from external ambient environmental conditions and contaminants for the purpose of maintaining sterility during product filling and sealing operations. The isolation protects against biological contamination and particulate matter from the surrounding environment while allowing product vessel transfer through entry and exit points. "Microenvironment" indicates a small-scale controlled space distinct from macro-scale clean rooms. This term does not encompass radiation isolation, which is addressed separately by the optional irradiation isolation module. The environment may be maintained through filtered air or inert gas systems, physical barriers, air curtains, or combinations thereof.

[0043] In the context of the disclosure, the term "irradiation isolation module", refers to a structure or system that attenuates, contains, or shields against radiation leakage from the E-Beam generator to ensure safety in areas adjacent to the sterilization module, particularly within or near the ambiently isolated packaging microenvironment. The module may comprise a multi-layer shielding structure with at least one high-Z layerfor radiation absorption and at least one low-Z layer for scattering secondary radiation, or alternatively may comprise a filtered gas curtain disposed within the ambiently isolated chamber. Either configuration alone is sufficient. The module functions to prevent harmful radiation exposure while permitting product vessel transfer between sterilization and packaging operations.

[0044] As used herein, the term "high-Z material", refers to a material composed of elements having high atomic number, suitable for attenuating electron beam and X-ray radiation through absorption. The specification identifies lead and tungsten as examples. A person of ordinary skill in radiation physics would understand high-Z materials as heavy elements, generally those with atomic numbers above approximately 50, selected for theireffectiveness in absorbing and stopping high-energy photons and charged particles through photoelectric effect and Compton scattering. No specific numerical atomic number threshold is required if the material effectively attenuates E-Beam or X-ray radiation as described.Conversely, the term "low-Z material" means a material composed of elements having low atomic number, suitable for scattering and dissipating secondary radiation produced when high-energy radiation interacts with high-Z shielding materials. The specification identifies polyethylene and boron-containing compounds as examples. A person of ordinary skill in radiation physics would understand low-Z materials as light elements, generally those with atomic numbers below approximately 20, which moderate and scatter secondary neutrons and photons through elastic scattering interactions. No specific numerical atomic number threshold is required if the material effectively scatters and dissipates secondary radiation as described.

[0045] As used herein, the term "actinic radiation at a UVC wavelength" means Electromagnetic radiation in the ultraviolet-C spectrum, approximately 100 to 280 nanometers wavelength, capable of producing photochemical reactions that inactivate microorganisms. In the context of this patent, the radiation serves a germicidal function to reduce bioburden on surfaces of the vessel or equipment within the ambiently isolated packaging microenvironment. "Actinic" emphasizes the photochemically active nature of the radiation but does not impose requirements beyond UVC wavelength, as UVC radiation is inherently actinic. The source must be operable to emit radiation at sufficient intensity and wavelength to sanitize surfaces as described.

[0046] “Filtered gas curtain” as used herein, refers to a flow of filtered gas directed in a curtain-like manner, e.g., “air knife”, within the ambiently isolated chamberto help contain radiation and / or contaminants while allowing transfer of materials through the region where the curtain is established.

[0047] In the context of the disclosure, the term “Module” refers to a subsystem of the overall system, comprising one or more components arranged to perform a particular function or set of related functions within the integrated sterilization-packaging system, such as sterilizing, handling, filling, sealing, or isolating irradiation. Additionally, the term “module”refers to a functional unit or subsystem comprising one or more components that work together to perform a specific function within the integrated sterilization-packaging system. A module is defined by its designated function and constituent components ratherthan requiring physical separation from other modules. Multiple modules may be integrated within a common housing, system, or apparatus and may share structural elements while maintainingtheir respective functional identities. Each module must be capable of performing its recited function, whether as a physically discrete unit or as a functionally distinct subsystem within an integrated machine. The term does not require separate housings, physical boundaries, or standalone operation capability unless specifically required by additional claim limitations.

[0048] In the context of the disclosure, the term "operable" means the system and / or the device and / orthe program, or a certain element orstep is fully functional, sized, adapted and calibrated, comprises elements for, and meets applicable operability requirements to perform a recited function when activated, coupled, implemented, actuated, effected, realized, or when an executable program is executed by at least one processor associated with the system and / or the device. In relation to systems and circuits, the term "operable" means the system and / orthe circuit is fully functional and calibrated, comprises logic for, havingthe hardware and firmware necessary, as well as the circuitry for, and meets applicable operability requirements to perform a recited function when executed by at least one processor.

[0049] As used herein, "product vessel" refers to a container composed of materials suitable for retaining liquids, solids, or compounds intended for medical or pharmaceutical product packaging. The vessel initially has sealed nozzles, entry points, or closures that maintain sterility during electron beam sterilization. Examples include intravenous fluid bags, bottles, vials, and syringes. The vessel is capable of being sterilized while sealed, transferred into the packaging microenvironment, opened or unsealed for filling with product, and then resealed to maintain sterility integrity. The term encompasses various container configurations, materials, and sizes suitable forthe described sterilization-filling-sealing process.

[0050] In the context of the disclosure, the term “sealed” refers to a product that is closed or covered sufficiently to maintain a sterile interior environment and prevent microbial contamination. A product vessel is sealed when its nozzles, entry points, or closures are configured to protect the interior from external contaminants during electron beam sterilization and transfer into the packaging microenvironment. The seal need not be hermetic or permanent but must be sufficient to maintain sterility integrity until the vessel is intentionally opened for filling. The sealed state allows irradiation of the vessel exterior while preserving interior sterility for subsequent filling with medical or pharmaceutical products. Furthermore, "unsealing" as used herein, means opening or removing a seal, closure, or barrier on a previously sealed product vessel to provide access to the vessel interior for filling operations. Methods of unsealing described in the specification include cutting nozzles, pulling caps, turning caps, or accessing septums for injection. Unsealing occurs within the ambiently isolated packaging microenvironment after the vessel has been sterilized and transferred from the sterilization module. The unsealing process must be performed using the material handling module in a manner that maintains the sterile microenvironment and prepares the vessel to receive the medical or pharmaceutical product.

[0051] Consequently, the term “sealing” as used herein, means closing or covering the product vessel after filling to restore closure integrity and maintain sterility of the contents. The product sealing module performs this function followingthe filling operation within the ambiently isolated packaging microenvironment. Sealing re-establishes protection against microbial contamination and maintains product sterility during subsequent storage, transport, and use. The seal must be sufficient to preserve sterility integrity as described in the specification. The sealing operation is performed using the material handling module and product sealing module before the filled vessel exits the ambiently isolated packaging microenvironment.

[0052] The term “coupled”, including its various forms such as “operably coupling”, "coupling" or "couplable", refers to and comprises any direct or indirect, structural coupling, connection or attachment, or adaptation or capability for such a direct or indirect structural or operational coupling, connection or attachment, including integrally formed components andcomponents which are coupled via or through another component or by the forming process. Indirect coupling may involve couplingthrough an intermediary member or adhesive, or abutting and otherwise resting against, whetherfrictionally or by separate means without any physical connection. Likewise, “operably coupled” refers to the joining of two members directly or indirectly to one another. Such joining may be stationary in nature or moveable in nature. Such joining may be achieved with the two members (or the two members and any additional intermediate) being integrally formed as a single unitary body with one another or with the two members or the two members and any additional members being attached to one another. Such joining may be permanent in nature or may be removable or releasable in nature.

[0053] Furthermore, "communicate" (and its derivatives e.g., a first component "communicates with" or "is in communication with" a second component) and grammatical variations thereof are used to indicate a structural, functional, mechanical, electrical, optical, orfluidic relationship, or any combination thereof, between two or more components or elements. As such, the fact that one component is said to communicate with a second component is not intended to exclude the possibility that additional components can be present between, and / or operatively associated or engaged with, the first and second components

[0054] The term "comprising" and its derivatives, as used herein, are intended to be open-ended terms that specify the presence of the stated features, elements, components, groups, integers, and / or steps, but do not exclude the presence of other unstated features, elements, components, groups, integers and / or steps. The foregoing also applies to words having similar meanings such as the terms, "including", "having" and their derivatives.

[0055] All ranges disclosed herein are inclusive of the endpoints, and the endpoints are independently combinable with each other. “Combination” is inclusive of blends, mixtures, alloys, reaction products, and the like. The terms “a”, “an” and “the” herein do not denote a limitation of quantity, and are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The suffix “(s)” as used herein is intended to include both the singular and the plural of the term that it modifies, therebyincluding one or more of that term (e.g., the vessel(s) includes one or more vessel). Reference throughout the specification to “one exemplary implementation”, “another exemplary implementation”, “an exemplary implementation”, and so forth, when present, means that a particular element (e.g., feature, structure, and / or characteristic) described in connection with the exemplary implementation is included in at least one exemplary implementation described herein, and may or may not be present in other exemplary implementations. In addition, it is to be understood that the described elements may be combined in any suitable manner in the various exemplary implementations.

[0056] All ranges disclosed herein are inclusive of the endpoints, and the endpoints are independently combinable with each other. Furthermore, the terms “first,” “second,” and the like, herein do not denote any order, quantity, or importance, but rather are used to denote one element from another.

[0057] Likewise, the term "about" means that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is "about" or "approximate" whether or not expressly stated to be such.

[0058] Accordingly, provided herein is an integrated sterilization-packaging system comprising: a point-of-use (POU) sterilization module; an ambiently isolated packaging microenvironment; and optionally an irradiation isolation module, wherein (i) the POU sterilization module comprises: a shielded processing chamber having, an entry and an exit; an E-Beam generator, operably coupled to the shielded processing chamber; and a product vessel transfer stage, operable to convey the product vessel sought to be sterilized through the shielded processing chamber, wherein the E-Beam generator is operable to adjust irradiation between about 0.1 MeV and about 40.0 MeV, (ii) the ambiently isolated packaging microenvironment comprises: an ambiently isolated chamber having an entry and an exit; a product filling module; a product sealing module; a material handling module, in communication with the product vessel transfer stage operable to transferthe product vesselfrom the ambiently isolated chamber entry, to the product filling module and the product sealing module and through the ambiently isolated chamber’s exit, the system (iii) further comprising the irradiation isolation module, (iv) the irradiation isolation module comprises at least one layer is composed of a high-Z material configured to attenuate E-Beam and / or X-ray radiation; and at least one other layer is composed of a low-Z material for scattering and dissipating secondary radiation, (v) and comprises a filtered gas curtain disposed within the ambiently isolated chamber, wherein (vi) the material handling module is further operable to unseal the product vessel, and (vii) is further operable to change positioning of the product vessel, and the system (viii), further comprising: a sub-system, configured to input filtered ambient air, or an inert gas into the ambiently isolated chamber; an electrostatic emitter; and a source of electromagnetic radiation, operable to emit actinic radiation at a UVC wavelength.

[0059] In another exemplary implementation, provided herein is a method of sterilizing a packaged medical and / or pharmaceutical product, implemented in a system comprising: a point-of-use (POU) sterilization module having a product vessel transfer stage, an ambiently isolated packaging microenvironment having a material handling module in communication with the product vessel transfer stage, and optionally an irradiation isolation module, wherein the method comprises the steps of: Irradiating a product vessel in the POU sterilization module, Transferringthe product vessel into the ambiently isolated packaging microenvironment, Filling the product vessel with the product, and Removing the product from the ambiently isolated packaging microenvironment, wherein (ix) the POU sterilization module comprises: a shielded processing chamber having, an entry and an exit, an E-Beam generator, operably coupled to the shielded processing chamber, and the product vessel transfer stage, operable to convey the product vessel sought to be sterilized through the shielded processing chamber, wherein the E-Beam generator is operable to adjust irradiation between about 0.1 MeV and about 40.0 MeV, (x) the ambiently isolated packaging microenvironment comprises: an ambiently isolated chamber having an entry and an exit, a product filling module, comprising a product sought to be packaged, a product sealing module, and the material handling module, operable to transfer the product vessel from the ambiently isolated chamber, to the product filling module and the product sealing moduleand through the ambiently isolated chamber’s exit, wherein (xi) the system further comprises the irradiation isolation module, (xii) the irradiation isolation module comprises at least one layer is composed of a high-Z material configured to attenuate E-Beam and / or X-ray radiation, and at least one other layer is composed of a low-Z material for scattering and dissipating secondary radiation, (xiii) and a filtered gas curtain disposed within the ambiently isolated chamber, the method further comprising (xiv) a step of: using the material handling module, unsealing the irradiated product vessel before the step of filling the product vessel, and using the material handling module, sealing the product vessel following the step of filling the product vessel, wherein (xv) the system further comprising: a sub-system, configured to input filtered ambient air, or an inert gas into the ambiently isolated chamber, an electrostatic emitter, and a source of electromagnetic radiation, operable to emit an actinic radiation at a UVC wavelength, the method further comprising (xvi): using the material handling module, changing the position of the product vessel before the step of filling, and (xvii), further comprising prior to the step of filling, or prior to the step of sealing, exposing the product sought to be packaged to the actinic radiation at a UVC wavelength, wherein (xviii) prior to the step of filling, or prior to the step of sealing, using the electrostatic emitter, eliminating buildup of electrostatic charge.

[0060] The above examples and description have of course been provided only for the purpose of illustration, and are not intended to limit the disclosed technology in anyway. As will be appreciated by the skilled person, the disclosed technology can be carried out in a great variety of ways, employing more than one technique from those described above, all without exceeding the scope of the invention.

Claims

What is claimed:

1. An integrated sterilization-packaging system comprising:a) a point-of-use (POU) sterilization module;b) an ambiently isolated packaging microenvironment; andc) optionally an irradiation isolation module.2 The system of claim 1 , wherein the POU sterilization module comprises:a) a shielded processing chamber having, an entry and an exit;b) an E-Beam generator, operably coupled to the shielded processing chamber; and c) a product vessel transfer stage, operable to convey the product vessel sought to be sterilized through the shielded processing chamber, wherein the E-Beam generator is operable to adjust irradiation between about 0.1 MeV and about 40.0 MeV.3 The system of claim 1 , wherein the ambiently isolated packaging microenvironment comprises:a) an ambiently isolated chamber having an entry and an exit;b) a product filling module;c) a product sealing module;d) a material handling module, in communication with the product vessel transfer stage operable to transfer the product vessel from the ambiently isolated chamber entry, to the product filling module and the product sealing module and through the ambiently isolated chamber’s exit.4 The system of claim 1 , further comprising the irradiation isolation module.5 The system of claim 4, wherein the irradiation isolation module comprises at least one layer is composed of a high-Z material configured to attenuate E-Beam and / or X-ray radiation; and at least one other layer is composed of a low-Z material for scattering and dissipating secondary radiation.6 The system of claim 4, wherein the irradiation isolation module comprises a filtered gas curtain disposed within the ambiently isolated chamber.7 The system of claim 3, wherein the material handling module is further operable to unsealthe product vessel.

8. The system of claim 3, wherein the material handling system is further operable to change positioning of the product vessel.

9. The system of claim 3, further comprising:a) A sub-system, configured to input filtered ambient air, or an inert gas into the ambiently isolated chamber;b) An electrostatic emitter;c) And a source of electromagnetic radiation, operable to emit actinic radiation at a UVC wavelength.

10. A method of sterilizing a packaged medical product, implemented in a system comprising: a point-of-use (POU) sterilization module having a product vessel transfer stage, an ambiently isolated packaging microenvironment having a material handling module in communication with the product vessel transfer stage, and optionally an irradiation isolation module, wherein the method comprises the steps of:a) Irradiating a product vessel in the POU sterilization module;b) Transferring the product vessel into the ambiently isolated packaging microenvi ronment;c) Filling the product vessel with the product; andd) Removingthe product from the ambiently isolated packaging microenvironment.

11. The method of claim 10, wherein the POU sterilization module comprises:a) a shielded processing chamber having, an entry and an exit;b) an E-Beam generator, operably coupled to the shielded processing chamber; and c) the product vessel transfer stage, operable to convey the product vessel sought to be sterilized through the shielded processing chamber, wherein the E-Beam generator is operable to adjust irradiation between about 0.1 MeV and about 40.0 MeV.

12. The method of claim 10, wherein the ambiently isolated packaging microenvironment comprises:a) an ambiently isolated chamber having an entry and an exit;b) a product filling module, comprising a product sought to be packaged;c) a product sealing module; andd) the material handling module, operable to transferthe product vessel from the ambiently isolated chamber, to the product filling module and the product sealing module and through the ambiently isolated chamber’s exit13. The method of claim 12 wherein the system further comprises the irradiation isolation module.

14. The method of claim 13, wherein the irradiation isolation module comprises at least one layer is composed of a high-Z material configured to attenuate E-Beam and / or X-ray radiation; and at least one other layer is composed of a low-Z material for scattering and dissipating secondary radiation.

15. The method of claim 13, wherein the irradiation isolation module comprises a filtered gas curtain disposed within the ambiently isolated chamber.

16. The method of claim 10, further comprising a step of: usingthe material handling module, unsealingthe irradiated product vessel before the step of fillingthe product vessel; and usingthe material handling module, sealing the product vessel followingthe step of filling the product vessel.

17. The method of claim 16, wherein the system further comprising:a) A sub-system, configured to input filtered ambient air, or an inert gas into the ambiently isolated chamber;b) An electrostatic emitter; andc) a source of electromagnetic radiation, operable to emit an actinic radiation at a UVC wavelength.

18. The method of claim 17, further comprising: usingthe material handling module, changing the position of the product vessel before the step of filling.

19. The method of claim 17, further comprising prior to the step of filling, or prior to the step of sealing, exposing the product sought to be packaged to the actinic radiation at a UVC wavelength.

20. The method of claim 17, further comprising prior to the step of filling, or prior to the step of sealing, usingthe electrostatic emitter, eliminating build up of electrostatic charge.21

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