Filling systems and active air monitoring thereof

Abstract

A filling system is provided that includes an isolator chamber, a filling chamber, an exterior door, and a transfer assembly. The exterior door has a first side in communication with an interior of the filling system and a second side in communication with an exterior of the filling system. The transfer assembly is removably couplable with the exterior door of the filling system. The transfer assembly includes a transfer assembly door configured to be couplable to and movable with the exterior door and an air monitoring capsule. The air monitoring capsule is positioned in an interior of the transfer assembly and is configured to continuously monitor one or more characteristics of the filling system.

Description

FILLING SYSTEMS AND ACTIVE AIR MONITORING THEREOF BACKGROUNDTechnical Field.

[0001] Examples of the subject matter herein relate generally to aseptic filling systems and methods, including aseptic systems and methods for filling of pharmaceutical containers with pharmaceuticals under controlled conditions, specifically active air monitoring thereof.Discussion of Art.

[0002] The process of filling pharmaceuticals into pharmaceutical containers is an important issue in the pharmaceuticals industry. As will be appreciated, such process are heavily regulated by various governmental and official bodies in various countries. As will be appreciated, pharmaceutical products need to be filled into the containers under very strict aseptic conditions, which present technical issues. Very specific procedures are specified for this task to a degree that makes the handling of pharmaceuticals profoundly different from the handling of any other industrial product, including specifically semiconductors, which also demand extreme and consistent environmental conditions. Indeed, the parallels between the handling of semiconductors in semiconductor “clean laboratories” and the handling of pharmaceuticals in aseptic isolators are superficial. They share the use of such “clean laboratories”, but there is no inherent aseptic requirement associated with semiconductor manufacture.

[0003] By its very nature, the production of sterile pharmaceuticals by humans can be problematic as humans can be a significant source of microbial contamination. Also, with increased potencies, some drugs can be hazardous in occupational exposure. For at least these reasons, robotics have been used in dosage manufacturing to limit human contact. Isolator technology, which provides a solid barrier between a process and humans, can also be used in dosage manufacturing to limit human contact.

[0004] To enable sterile processing, isolator technology has evolved to adapt various vapor and gas sterilization systems, thereby bringing about an advance in aseptic processing. Articulated cleanroom robots have been employed which utilize internal negative pressure with an exhaust to generate cleanroom capability. With the chemical sterilization and handling of potent drugs within the isolator, an internal negative pressure cleanroom with an exhaust is not generally feasible, due largely to the leakage potential.

[0005] Monitoring of the various chambers provides information relating to the efficacy of the product being filled as well as potential contamination status. Currently, monitoring of the chambers occurs for a limited sampling time before being removed and tested. Continuous monitoring of the chambers may be exceedingly difficult, expensive, or not possible using existing systems.

[0006] It may be desirable to have improvements in design and methods of use of air monitoring in filling systems in order to facilitate a more reliable, sterile, and efficient process. It may be desirable to have a system and method that differs from those that are currently available.BRIEF DESCRIPTION

[0007] In accordance with an aspect of the invention, a filling system is described. The filling system includes an isolator chamber, a filling chamber, an exterior door, and a transfer assembly. The exterior door has a first side in communication with an interior of the filling system and a second side in communication with an exterior of the filling system. The transfer assembly is removably couplable with the exterior door of the filling system. The transfer assembly includes a transfer assembly door and an air monitoring capsule. The transfer assembly door is configured to be couplable to and movable with the exterior door. The air monitoring capsule may be positioned in an interior of the transfer assembly. The air monitoring capsule may be configured to continuously monitor one or more characteristics of the filling system.

[0008] In an embodiment, the transfer assembly may include a connection means to couple the transfer assembly to the filling chamber or the isolator chamber. The connection meansmay include one or more of a friction fit, a snap fit, an interference fit, a quarter-turn connection, or the like.

[0009] In an embodiment, the exterior door and the transfer assembly door may be openable.

[0010] In an embodiment, the transfer assembly may include one or more seals that may be configured to selectively seal the air monitoring capsule.

[0011] In an embodiment, the one or more characteristics may include a viable cell count.

[0012] In an embodiment, the exterior door may be coupled with the transfer assembly door responsive to the transfer assembly being coupled to the filling system. In an embodiment, the filling system may include a filling chamber door that is configured to be in communication with the transfer assembly door of the transfer assembly responsive to the transfer assembly being coupled to the filling chamber.

[0013] In accordance with another aspect of the invention, a method for filling containers with a pharmaceutical product is described. The method includes sterilizing a transfer assembly in a first chamber, installing the transfer assembly in a second chamber, exposing an air monitoring capsule of the transfer assembly to an interior of the second chamber, removing the transfer assembly from the second chamber and placing the transfer assembly into the first chamber, and monitoring the air monitoring capsule for one or more characteristics of the second chamber.

[0014] In an embodiment, the method may include providing one or more filters in the transfer assembly. The method may include providing one or more seals in the transfer assembly.

[0015] In an embodiment, the method may include providing a connection means on the transfer assembly. The connection means may be configured to selectively couple the transfer assembly with the first chamber and the second chamber.

[0016] In one embodiment, the one or more characteristics may include a viable cell count.

[0017] In one embodiment, the air monitoring capsule may be sealed from an external environment when the transfer assembly is not coupled to the first chamber or the second chamber.

[0018] In accordance with yet another aspect of the invention, a method for filling containers with a pharmaceutical product within a chamber configured to maintain an aseptic condition is described. The method includes providing the chamber with a removable transfer assembly. The removable transfer assembly having a seal with the chamber. The method further includes providing an air monitoring capsule in communication with the removable transfer assembly and monitoring a viable particle count using the air monitoring capsule.

[0019] In an embodiment, the air monitoring capsule may be a single use active air monitoring chamber.

[0020] In an embodiment, the method may include coupling the chamber with the removable transfer assembly via a snap fit connection means.

[0021] In an embodiment, the method may include sterilizing the removable transfer assembly in an isolator chamber prior to providing the chamber with the removable transfer assembly.

[0022] In an embodiment, the method may include providing one or more filters in the removable transfer assembly.

[0023] In an embodiment, the air monitoring capsule may be configured to be sealed from an external environment when the removable transfer assembly is removed from the chamber.

[0024] In accordance with one aspect of the invention, a transfer assembly configured for attachment to a filling system is described. The transfer assembly includes a first end, a second end, a connection means, and an air monitoring capsule. The second end ispositioned opposite the first end. The second end includes an openable door. The connection means is configured to removably couple the transfer assembly to a filling chamber of the filling system. The air monitoring capsule is positioned between the first end and the second end. The air monitoring capsule is configured to monitor one or more characteristics of the filling system.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The subject matter may be understood from reading the following description of non-limiting examples, with reference to the attached drawings, wherein below:

[0026] Fig. l isa top view of a filling system, according to an embodiment of the invention;

[0027] Fig. 2 is a cross-sectional view of a filling system, according to an embodiment of the invention;

[0028] Fig. 3 is a top view of a filling system showing an airflow, according to an embodiment of the invention;

[0029] Fig. 4 is another top view of a filling system showing an airflow, according to an embodiment of the invention;

[0030] Fig. 5 is a top view of a vacuum chamber with a door in a closed position, according to one example;

[0031] Fig. 6 is a top view of a vacuum chamber with a door in an open position, according to one example;

[0032] Fig. 7 is a perspective view of a filling system with a door of a vacuum chamber in a closed position and an open position, according to one example;

[0033] Fig. 8 is a front view of a diffuser of a filling system, according to one example;

[0034] Fig. 9a is a front view of a diffuser of a filling system, according to one example;

[0035] Fig. 9b is a front view of a diffuser of a filling system, according to another example;

[0036] Fig. 10 is a cross-sectional view of a transfer assembly of a filling system, according to one example; and

[0037] Fig. 11 is a schematic diagram of a transfer assembly and a chamber of a filling system, according to one example.DETAILED DESCRIPTION

[0038] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0039] Embodiments of the subject matter described herein may relate to a filling system, for example an aseptic filling system. Specifically, a system with a vacuum chamber with an active airflow that may be controlled for desired airspeeds under dynamic conditions, and a method thereof.

[0040] Fig. 1 illustrates filling system 100 that is configured to fill containers 102 with a product, according to an embodiment of the invention. The filling system 100 may be an aseptically sealed robotic filling system. The product may be at least one of a liquid product, a pharmaceutical product, a potentially toxic or harmful product, or the like, for example. The containers of the filling system may include vials, syringes, bottles, beakers, test tubes, or the like suitable for containing a product, for example a pharmaceutical product.

[0041] In embodiment, the filling system 100 may include a filling chamber 110, a decontamination and staging isolator (DSI) chamber 120, and a stoppering vacuum chamber (SVC) 130. The chambers may work together to maintain an aseptic environment to prepare, fill, and stopper the products into the containers. The filling chamber 110 may be an isolator chamber capable of maintaining an aseptic condition within the chamber. In one example, the filling chamber 110 is the compartment of the filling system where the containers are filled with a designated product. The filling chamber 110 may be coupled with the DSI 120 and the SVC 130.

[0042] The DSI chamber 120 may maintain an aseptic environment and may hold the containers 102 before filling in the filling chamber 110. Once the containers 102 are ready to be filled, the containers may be transferred from the DSI chamber 120 to the filling chamber 110 via a port 121. The DSI chamber 120 is intended to be a sterile, contaminant free area. The DSI chamber 120 may include air flow and / or other features (e.g., disinfectant solutions, disinfectant light, etc.) that may be intended to remove contaminants and sterilize the DSI chamber 120. The DSI chamber 120 may be designed to be separated from the filling chamber 110 by an openable door that may be sealed except when the containers are being moved from the DSI chamber 120 to the filling chamber 110. The containers may be moved from the DSI chamber 120 to the filling chamber 110 by one or more arms, discussed further below. Further, a removable transfer port or assembly may be couplable with the DSI chamber 120, as discussed further below with respect to FIGS.10 and 11.

[0043] The filling system 100 may include one or more proximity sensors or other suitable devices capable of sensing when a transfer container is engaged with at least one port. This arrangement prevents opening of the at least one port while not engaged with a transfer container and avoids contamination of the interior environmental condition. The filling system 100 may include one or more glove holes disposed in the walls of the filling chamber 110. The glove holes may be used to manually manipulate objects within the filling chamber 110 without opening the filling chamber 110 or otherwise compromising the environmental condition within the filling chamber 110.

[0044] The filling chamber 110 may include one or more filling arms 112. The filling arms 112 may be a compound articulated robotic arm. The arms 112 may include filling tubing extending from a pump to a point at an end of the arms. An outlet of the tube may include a valve, filling needle, or other flow control device to control discharge of the product from the filling tubing. The arms 112 may transport each container 102 individually, or may transport a tray or other vessel containing more than one container 102. The arm 112 maybe used to perform multiple tasks, for example, transporting containers, holding containers, openings doors or ports of the filling system, or the like.

[0045] The arms 112 may be controlled by a controller 111. The controller may include microcontrollers, processors, microprocessors, or other logic devices that operate based on instructions stored on a tangible and non-transitory computer readable storage medium, such as software applications stored on a memory.

[0046] The filling system 100 may include one or more sensors for sensing containers within the filling chamber 110. The sensors may be an optical sensor, a pressure sensor, a camera, Hall effect sensors, or the like. The sensors may locate and provide an orientation of the containers. The positions identified by the sensors may be used to direct or guide the filling arms to fill the containers with the product. Additionally, the sensors may inspect the containers prior to filling to identify any defects, irregularities, and / or abnormalities for inspection.

[0047] The containers 102 are filled in the filling chamber and then may be moved by the arms 112 to the stoppering vacuum chamber 130. The stoppering vacuum chamber 130 may include an arm 133 that receives the containers 102 and places closures to close the containers. The closures may include lyophilization stoppers, serum stoppers, syringe stoppers, and the like. Prior to the stopper being placed, a blower (discussed further below) may activate a unidirectional airflow across a top portion of the containers 102. The airflow may reduce contamination risk by removing contaminants from the stoppering vacuum chamber. Once the airflow through the stoppering vacuum chamber 130 is complete, the stoppers may be placed on the containers 102.

[0048] The arms 112, 133 may be a servo-driven robotic arm. In other examples, the arms 112, 133 can be of differing configurations, provided they are capable of functioning in the manners described herein. In one example, the arms 112, 133 may be manually driven or directed by an operator of the filling system.

[0049] The stoppering vacuum chamber 130 may be in fluid communication with a blower 150. The blower 150 moves air through the stoppering chamber by way of tubing 152 that connects the blower 150 and the stoppering vacuum chamber 130. The size and speed settings of the blower 150 may be adjusted based on the desired use characteristics. Additionally, the diameter and length of the tubing 152 may be adjusted based on the size and desired airflow characteristics of the filling system. In one example, the blower provides unidirectional air flow to the stoppering vacuum chamber. In one example, the tubing 152 includes a valve 154 between the blower 150 and the stoppering vacuum chamber 130. The valve 154 may be a vacuum-rated valve that isolates and seals the stoppering vacuum chamber from an external environment. In FIG. 2, the blower 150 is shown spaced apart from the stoppering vacuum chamber, however, in another embodiment the blower may be positioned within the stoppering vacuum chamber, for example in a door of the stoppering vacuum chamber.

[0050] This arrangement allows unidirectional airflow through the stoppering vacuum channel 130, within a specific air speed range. This allows minimized turbulence and air backflow. The airflow may be actively controlled (e.g., by sensors, discussed below) to maintain desired speeds under dynamic conditions. For example, if the sensors detect an air speed outside of a predetermined range, the controller may direct the blower to increase or decrease the air speed such that the air speed is within the predetermined range.

[0051] One or more sensors 156 may be positioned in the tubing 152 to monitor the characteristics of airflow, for example the airflow rate entering the stoppering vacuum chamber 130. The one or more sensors may include an anemometer. The anemometer is capable of measuring an air speed and direction within the stoppering vacuum chamber and / or the tubing. The sensors may be positioned at approximately a mid-point of the tubing, as shown in FIG. 2. However, in other examples, the sensors may be positioned closer to the stoppering vacuum chamber, closer to the blower, or at multiple points. The sensors may be in communication with the controller. Additionally, the controller may direct action of the components of the filling system, for example, the sensors, the arms,the blower, the valve, and the like. This allows the system to keep air speed within desired ranges.

[0052] The stoppering vacuum chamber 130 may include a filter 134 positioned to filter the airflow from the blower prior to entering the stoppering vacuum chamber 130. The filter 134 may be a HEP A filter that provides aseptic airflow protection to an interior of the stoppering vacuum chamber 130. The HEPA filtration of unidirectional air meets the “first air” principle where HEPA filtered air arrives undisturbed at the containers being stoppered, providing aseptic protection over the exposed contents of the containers. In another example, airflow may exit the stoppering vacuum chamber 130. Air may be moved or sucked out of the stoppering vacuum chamber 130.

[0053] A diffuser 132 may be positioned downstream of the filter 134 to modify air entering the stoppering vacuum chamber 130. The diffuser 132 may be seen as a last line of defense against particulate contamination, as it is downstream of the filter 134. The unidirectional airflow through the diffuser 132 may exhibit waves as the air travels. Any particles that travel in this air stream will follow this wave pattern. The wave pattern may increase risk of particle ingress into containers being protected by the airflow.

[0054] The design of the diffuser may be precisely designed based on the filling apparatus and desired airflow. FIG. 8 illustrates a diffuser 132 according to one example. The diffuser 132 of FIG. 8 contains a plurality of apertures 180 along a body 181 of the diffuser that direct airflow through the diffuser 132. The airflow is impacted by the plurality of apertures 180 but the airflow is not specifically targeted and generally results in a wave pattern in the airflow. FIG. 9a, however, illustrates a diffuser 132 having a plurality of apertures 180, as well as one or more gaps 182, according to one example.

[0055] The gaps 182 and apertures 180 may be selected to provide a desired airflow pattern through the diffuser. In one example, the gaps 182 may be positioned in a central portion of the body 181. The gaps 182 may be positioned here to specifically modify the airflow to increase air flow protection. The gaps 182 and apertures 180 may be modified based onthe particular type and size filling apparatus, the filling product, the containers, or the like. The wave pattern of the airflow can be minimized or removed based on the diffuser arrangement, thus providing better airflow protection. Said another way, the diffuser gaps or apertures may facilitate more straight-line airflow, reducing waves and eddies in the airflow.

[0056] The gaps 182 may be strategically input to allow for better airflow protection, with higher air speed, with reduced turbulence and waves. As shown in FIG. 9a, there may be three rows of gaps 182. However, in other examples, there may be more or less rows of gaps. Additionally, as shown in FIG. 9a, each row may have a different number of gaps, however, in other examples, each row may have the same number of gaps. As discussed, the gaps may be selected based on the desired airflow pattern, airflow speed, filling apparatus, or the like.

[0057] As illustrated in FIG. 9b, the size and arrangement of the apertures 180 may be varied. The apertures 180 may be arranged in a grid array. The apertures 180 may be modified and / or optimized to achieve desired airflow characteristics. The density of the apertures may be varied throughout the body 181 of the diffuser to achieve the desired airflow characteristics.

[0058] The diffuser 132 may be designed to be removable from the filling apparatus. As such, the diffuser may be customized based on the desired airflow speed and / or pattern for a particular product. This customizability allows for a more efficient, less contaminated, and more tailored performance of the filling apparatus.

[0059] A plenum 158 may be positioned on an outer wall of the door 136, as illustrated in FIG. 7. The plenum 158 may provide additional structural stiffness to the door 136. The size and curvature of the plenum 158 may be adjusted based on the structural properties needed. In one example, the plenum 158 may include stiffening ribs to enhance the stiffness, while still allowing airflow to sufficiently mix and pressure-equalize before passing through the filter. The enhanced structural stiffness may aid in withstandingvacuum pressures, as well as withstanding large actuation forces in the stoppering process. This may reduce the complexity and contamination risks associated with the filling and stoppering of the containers.

[0060] The vacuum chamber 130 may include a door 136, as shown in FIGS. 5 and 6. FIG.5 illustrates a door 136 of the vacuum chamber 130 in a closed position, according to one example. FIG. 6 illustrates a door 136 of the vacuum chamber 130 in an open position, according to one example. The door 136 may be coupled to the stoppering vacuum chamber 130 via a hinge 138. The hinge 138 may be coupled to an adaptor plate 137 of the vacuum chamber 130. The coupling may have sealing surfaces 139. The sealing surfaces 139 may be configured to maintain a seal within the vacuum chamber 130 to allow a vacuum within the chamber. The door 136 may be openable to allow access to an interior of the stoppering vacuum chamber 130 for wipe down cleaning, inspection, maintenance, and the like. The hinged access door allows easy access to the interior space of the stoppering vacuum chamber.

[0061] In one embodiment, the door 136 may be sized and designed to contain components contributing to the air flow through the vacuum chamber 130. For example, the blower, the filter, the diffuser, the plenum, the valve, and / or the tubing may be mounted within the door. This may allow for easy operator access to internals, while still providing a seal under vacuum and positive pressure. In another example, one or more of the components may be positioned outside the door but may be in fluid communication with the door, such that the airflow may be directed through the vacuum chamber.

[0062] FIGS. 3 and 4 illustrate airflow of filling systems 100, according to one example. There is an airflow 113b entering the filling chamber 110. The airflow 113b may be driven by a blower or other device. Air in the filling chamber 110 may be exhausted 115 into the DSI chamber 120. In one example, the air in the DSI chamber may be configured to continuously move and / or swirl through the DSI chamber. It is further contemplated that air from the filling chamber 110 exhausts to a recirculation loop, and from the recirculation loop a portion of air may be exhausted out of the cleanroom while another portion isrecirculated back into the filling chamber inlet filters, with an additional top-up of air from another blower drawing air from cleanroom.

[0063] As discussed above, the stoppering vacuum chamber 130 may include a blower that is configured to direct air 113a across and through the stoppering vacuum chamber and into the filling chamber 110. As previously discussed, this unidirectional airflow minimizes turbulence and backflow while meeting the “first air” principle to provide aseptic protection over the containers.

[0064] FIG. 10 illustrates a transfer assembly 300 that may be removably coupled with the filling system 100, according to one example. The transfer assembly 300 may be manually introduced to the filling system 100, for example the filling chamber 110, the DSI chamber 120, or the like. The transfer assembly 300 may include a first end 310 and a second end 320 positioned opposite the first end 310. The second end 320 may include an openable door 322. The door 322 may be openable when the transfer assembly 300 is coupled with a chamber.

[0065] An air monitoring capsule 330 is positioned in an interior of the transfer assembly 300, between the first end 310 and the second end 320. When the transfer assembly 300 is coupled to the filling chamber 110, the air monitoring capsule 330 may monitor one or more characteristics of the filling chamber. The one or more characteristics may include a viable cell count, a contamination level, or the like.

[0066] The transfer assembly 300 may include one or more seals 335 and one or more filters 337. The seals 335 may isolate the air monitoring capsule 330 from the external environment, thereby reducing the risk of contamination. The filters 337 may reduce the risk of contamination as well. Additionally, the filters 337 may equalize the pressure inside the transfer assembly 300.

[0067] The transfer assembly 300 may include a connection means 350 to removably couple air monitoring capsule 330 to the transfer assembly 300. The connection means 350 may be a snap fit, a friction fit, an interference fit, a quarter-turn connection, or the like.The connection means 350 provides a quick, simple, and reliable connection to firmly hold the air monitoring capsule 330 in place within the transfer assembly 300.

[0068] In practice, the transfer assembly 300 may be prepared in a separate staging isolator and then coupled with the filling chamber. The transfer assembly 300 may be manually inserted by a user or may be inserted using one or more of the arms discussed above, directed by the controller or user input. Once the transfer assembly 300 is sterilized, the transfer assembly may be sealed and may be inserted into the filling chamber 110. Once inserted, the openable door 322 may open, along with a corresponding door on the filling chamber, shown and described further below with respect to FIG. 11. The outer portions of the openable door 322 and the filling chamber door may be positioned to be in contact, such that contamination from the outer portions is not exposed to the interior of the filling chamber 110. Said another way, exterior walls, that are exposed to the external environment in an uncoupled position, of the openable door 322 and the filling chamber door are sized and positioned to couple to one another such that the exterior walls mate, and thus exposed portions are not introduced to the filling chamber. The air monitoring capsule 330 may then be exposed to the interior of the fill chamber 110 and may monitor one or more characteristics of the interior of the fill chamber 110. The air monitoring capsule 330 may be capable of continuously monitoring the fill chamber 110 when coupled.

[0069] After a predetermined amount of time, the door 322 of the transfer assembly 300 may be closed and the transfer assembly 300 may be removed from the filling chamber 110. The door 322 may be closed to keep the air monitoring capsule 330 sterile when removed. The transfer assembly 300 may then be sent to be disassembled and may be sent for incubation. Typically, the disassembly and incubation may occur in a separate system and / or facility. Upon removal of the transfer assembly 300 from the filling chamber, another transfer assembly may be inserted into the filling chamber 110 to maintain monitoring of the filling chamber 110. This allows for continuous particle monitoring.

[0070] FIG. 11 shows a schematic diagram of the transfer assembly 300 and the filling chamber 110 of the filling system 100, according to one example. The transfer assembly 300 is coupled with the filling chamber 110, where a door 119 of the filling chamber 110 is closed and the door 322 of the transfer assembly 300 is closed. As shown, the doors 119 and 322 are positioned to have an outer exposed portion touching. When the transfer assembly 300 is uncoupled to the filling system 100, the outer exposed portions are exposed to ambient or external air, which exposes the outer exposed portions to potential contaminants. A vacuum pump 333 may be coupled with a filter 337 of the transfer assembly 300. The doors 119 and 322 are configured to be removably couplable to one another. Additionally, the doors 119 and 322 are configured to be movable together. The doors 119 and 322 mate together and form a seal, isolating the outer exposed portions from an interior of the filling system. The doors 119 and 322 move together to open, allowing fluid communication between the interior of the transfer assembly and the interior of the filling system. Once the doors are opened, or concurrently with the doors being opened, the vacuum may be pulled to expose the air monitoring capsule 330 to the interior of the filling chamber 110. The air monitoring capsule 330 may begin a sampling process.

[0071] After a predetermined amount of time, the sampling period may be ended, the doors 119 and 322 may be closed, and the vacuum pump may be disconnected. The predetermined amount of time may be based on the filling system and may be between 1 hour and 12 hours. However, the predetermined amount of time may be greater or less than this amount of time, in other examples. The transfer assembly 300 may then be removed and inserted into a separate staging isolator for disassembling the air monitoring capsule 330 for incubation. Another transfer assembly 300 may then be inserted into the filling chamber following the same procedure.

[0072] A method of operating a stoppering vacuum chamber of a filling apparatus is also provided. The method includes providing airflow from a blower through the stoppering vacuum chamber, filtering the airflow through the stoppering vacuum chamber, and diffusing air exiting the stoppering vacuum chamber.

[0073] In one embodiment, a filling system is described. The filling system includes an isolator chamber, a filling chamber, an exterior door, and a transfer assembly. The exterior door has a first side in communication with an interior of the filling system and a second side in communication with an exterior of the filling system. The transfer assembly is removably couplable with the exterior door of the filling system. The transfer assembly includes a transfer assembly door configured to be couplable to and movable with the exterior door and an air monitoring capsule. The air monitoring capsule may be positioned in an interior of the transfer assembly. The air monitoring capsule may be configured to continuously monitor one or more characteristics of the filling system.

[0074] In one example, the transfer assembly door may include a connection means to couple the transfer assembly door to the second side of the exterior door. The connection means may include one or more of a friction fit, a snap fit, an interference fit, a quarterturn connection, or the like. In one example, the exterior door and the transfer assembly door may be openable.

[0075] In one example, the transfer assembly may include one or more seals that may be configured to selectively seal the air monitoring capsule. The one or more characteristics may include a viable cell count.

[0076] In one example, the exterior door may be configured to be coupled with the transfer assembly door responsive to the transfer assembly being coupled to the filling system.

[0077] In one embodiment, a method for filling containers with a pharmaceutical product is described. The method includes sterilizing a transfer assembly in a first chamber, installing the transfer assembly in a second chamber, exposing an air monitoring capsule of the transfer assembly to an interior of the second chamber, removing the transfer assembly from the second chamber and placing the transfer assembly into the first chamber, and monitoring the air monitoring capsule for one or more characteristics of the second chamber.

[0078] In one example, the method may include providing one or more filters in the transfer assembly. The method may include providing one or more seals in the transfer assembly.The method may include providing a connection means on the transfer assembly. The connection means may be configured to selectively couple the transfer assembly with the first chamber and the second chamber.

[0079] In one example, the one or more characteristics may include a viable cell count. The air monitoring capsule may be sealed from an external environment when the transfer assembly is not coupled to the first chamber or the second chamber.

[0080] In one embodiment, a method for filling containers with a pharmaceutical product within a chamber configured to maintain an aseptic condition is described. The method includes providing the chamber with a removable transfer assembly. The removable transfer assembly having a seal with the chamber. The method further includes providing an air monitoring capsule in communication with the removable transfer assembly and monitoring a viable particle count using the air monitoring capsule.

[0081] In one example, the air monitoring capsule may be a single use active air monitoring chamber. The method may include coupling the chamber with the removable transfer assembly via a snap fit connection means.

[0082] In one example, the method may include sterilizing the removable transfer assembly in an isolator chamber prior to providing the chamber with the removable transfer assembly.

[0083] In one example, the method may include providing one or more filters in the removable transfer assembly. The air monitoring capsule may be configured to be sealed from an external environment when the removable transfer assembly is removed from the chamber.

[0084] In one embodiment, a transfer assembly configured for attachment to a filling system is described. The transfer assembly includes a first end, a second end, a connection means, and an air monitoring capsule. The second end is positioned opposite the first end. The second end includes an openable door. The connection means is configured toremovably couple the transfer assembly to a filling chamber of the filling system. The air monitoring capsule is positioned between the first end and the second end. The air monitoring capsule is configured to monitor one or more characteristics of the filling system.

[0085] As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” do not exclude the plural of said elements or operations, unless such exclusion is explicitly stated. Furthermore, references to “one embodiment” of the invention do not exclude the existence of additional embodiments that incorporate the recited features. Moreover, unless explicitly stated to the contrary, embodiments “comprising,” “comprises,” “including,” “includes,” “having,” or “has” an element or a plurality of elements having a particular property may include additional such elements not having that property. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.” Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and do not impose numerical requirements on their objects. Further, the limitations of the following claims are not written in means-plus-function format and are not intended to be interpreted based on 35 U.S.C. § 112(f), unless and until such claim limitations expressly use the phrase “means for” followed by a statement of function devoid of further structure.

[0086] The above description is illustrative, and not restrictive. For example, the abovedescribed embodiments (and / or aspects thereof) may be used in combination with each other. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the inventive subject matter without departing from its scope. While the dimensions and types of materials described herein define the parameters of the inventive subject matter, they are exemplary embodiments. Other embodiments will be apparent to one of ordinary skill in the art upon reviewing the above description. The scope of the inventive subject matter should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

[0087] Use of phrases such as “one or more of ... and,” “one or more of ... or,” “at least one of ... and,” and “at least one of ... or” are meant to encompass including only a single one of the items used in connection with the phrase, at least one of each one of the items used in connection with the phrase, or multiple ones of any or each of the items used in connection with the phrase. For example, “one or more of A, B, and C,” “one or more of A, B, or C,” “at least one of A, B, and C,” and “at least one of A, B, or C” each can mean (1) at least one A, (2) at least one B, (3) at least one C, (4) at least one A and at least one B, (5) at least one A, at least one B, and at least one C, (6) at least one B and at least one C, or (7) at least one A and at least one C.

[0088] This written description uses examples to disclose several embodiments of the inventive subject matter, including the best mode, and to enable one of ordinary skill in the art to practice the embodiments of inventive subject matter, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the inventive subject matter is defined by the claims, and may include other examples that occur to one of ordinary skill in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.

Claims

WHAT IS CLAIMED IS:

1. A filling system, comprising:an isolator chamber;a filling chamber;an exterior door having a first side in communication with an interior of the filling system and a second side in communication with an exterior of the filling system; and a transfer assembly that is removably couplable with the exterior door of the filling system, the transfer assembly includinga transfer assembly door configured to be couplable to and movable with the exterior door, andan air monitoring capsule positioned in an interior of the transfer assembly, wherein the air monitoring capsule is configured to continuously monitor one or more characteristics of the filling system.

2. The filling system of claim 1, wherein the transfer assembly door includes a connection means to couple the transfer assembly door to the second side of the exterior door.

3. The filling system of claim 2, wherein the connection means includes one or more of a friction fit, a snap fit, an interference fit, a quarter-turn connection, or the like.

4. The filling system of claim 1, wherein the exterior door and the transfer assembly door are configured to be openable.

5. The filling system of claim 1, wherein the transfer assembly includes one or more seals that are configured to selectively seal the air monitoring capsule.

6. The filling system of claim 1, wherein the one or more characteristics includes a viable cell count.

7. The filling system of claim 1, wherein the exterior door is configured to be coupled with the transfer assembly door responsive to the transfer assembly being coupled to the filling system.

8. A method for filling containers with a pharmaceutical product, the method comprising:sterilizing a transfer assembly in a first chamber;installing the transfer assembly in a second chamber;exposing an air monitoring capsule of the transfer assembly to an interior of the second chamber;removing the transfer assembly from the second chamber and placing the transfer assembly into the first chamber; andmonitoring the air monitoring capsule for one or more characteristics of the second chamber.

9. The method of claim 8, further comprising providing one or more filters in the transfer assembly.

10. The method of claim 8, further comprising providing a connection means on the transfer assembly, the connection means configured to selectively couple the transfer assembly with the first chamber and the second chamber.

11. The method of claim 8, wherein the one or more characteristics includes a viable cell count.

12. The method of claim 8, further comprising providing one or more seals in the transfer assembly.

13. The method of claim 12, wherein the air monitoring capsule is sealed from an external environment when the transfer assembly is not coupled to the first chamber or the second chamber.

14. A method for filling containers with a pharmaceutical product within a chamber configured to maintain an aseptic condition, the method comprising:providing the chamber with a removable transfer assembly, the removable transfer assembly having a seal with the chamber;providing an air monitoring capsule in communication with the removable transfer assembly; andmonitoring a viable particle count using the air monitoring capsule.

15. The method of claim 14, wherein the air monitoring capsule is a single use active air monitoring chamber.

16. The method of claim 14, further comprising coupling the air monitoring capsule with the removable transfer assembly via a snap fit connection means.

17. The method of claim 14, further comprising sterilizing the removable transfer assembly in an isolator chamber prior to providing the chamber with the removable transfer assembly.

18. The method of claim 14, further comprising providing one or more filters in the removable transfer assembly.

19. The method of claim 14, wherein the air monitoring capsule is configured to be sealed from an external environment when the removable transfer assembly removed from the chamber.

20. A transfer assembly configured for attachment to a filling system, comprising: a first end;a second end opposite the first end, the second end including an openable door; a connection means configured to removably couple the transfer assembly to a filling chamber of the filling system; andan air monitoring capsule positioned between the first end and the second end, wherein the air monitoring capsule is configured to monitor one or more characteristics of the filling system.

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