Fluid distribution system having single-use manifold fluid recovery assembly

Abstract

To provide a novel fluid distribution system.SOLUTION: A fluid distribution system includes single-use distribution manifolds each having a distribution manifold inlet and a plurality of distribution manifold outlets in fluid communication with the distribution manifold inlet. A set of single-use filler manifolds can be sequentially connected to a corresponding one of the outlets of a single-use distributor manifold immediately upstream of a connection point of the set of single-use filler manifolds. In embodiments, an upstream distributor manifold can be used to feed fluid to a set of intermediary distributor manifolds where the set of intermediary distributor manifolds corresponds to the number of outlets of the upstream distributor manifold.SELECTED DRAWING: Figure 1

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This patent application claims priority to U.S. Provisional Patent Application No. 63 / 295,490, filed December 30, 2021, entitled "Fluid Distribution System with Single Use Manifold Fluid Recovery Assembly," and claims the benefit of priority to U.S. Non-Provisional Patent Application No. 17 / 934,486, filed September 22, 2022, entitled "Distribution System with Single Use Manifold Fluid Recovery Assembly," which provisional patent applications are incorporated herein by reference in their entireties. [Background technology]

[0002]

[0002] The use of single-use systems (SUS), such as biocontainer bags, is becoming increasingly popular for biopharmaceutical applications. SUS can be used in systems such as bioreactors and mixing systems. Exemplary upstream SUS applications include media preparation processes such as mixing and filtration, including tangential flow filtration (TFF). Examples of downstream SUS applications include chromatography concentration and diafiltration and buffer preparation.

[0003]

[0003] The adoption of SUS can offer several advantages over traditional reusable stainless steel systems: Single-use technology can increase process flexibility, reduce the risk of cross-contamination, reduce or even eliminate the need for cleaning, reduce the requirements for room sterilization, such as by autoclaving, and cleaning of chemical inventory, and reduce process downtime.

[0004]

[0004] One aspect of biopharmaceutical processing involves managing the movement of fluids through various elements, including tubing, valves, and sensors. There is a particular need for bulk filling processes that dispense fluids from large containers into multiple individual containers while maintaining sterility.

[0005] In conventional systems, fluid can remain in the manifold of a fluid distribution system after a fill sequence has been performed. For a typical pharmaceutical liquid, the cost per milliliter of product can be thousands of dollars. In some cases, an operator can manually manipulate the manifold to pump fluid from the manifold into a "leftover" container each time it is replaced. These containers are "leftover" because they do not contain the exact volume as the customer-filled containers; therefore, the fluid in them is often discarded, used for offline analysis, or otherwise not included in the final formulation. This not only represents a costly loss, but it also reduces the amount of drug produced in the final formulation, reducing the number of drug doses per batch for patient treatment.

[0006]

[0006] There is a continuing need in the art for single-use applications involving the distribution of fluid from a source into several smaller containers. For example, there is a continuing need in the art to provide additional solutions for aseptically dispensing liquids into a significant number of outlets, and thus into containers such as bags and bottles, while reducing the amount of fluid wasted during the filling operation.

[0007] It will be understood that this background discussion is provided to assist the reader and that none of the problems presented should be construed as indicating that they have been recognized in the art. While the principles described may, in some aspects and embodiments, alleviate problems inherent in other systems, it will be understood that the scope of the innovation protected is defined by the appended claims, and not by the ability of any disclosed feature to solve the particular problem described herein. Summary of the Invention

[0008]

[0008] In one aspect, the present disclosure relates to an embodiment of a fluid distribution system, in one embodiment, the fluid distribution system includes a pump, a single-use filling manifold, a filling valve apparatus, and a control unit.

[0009] The pump is configured to selectively generate a fluid flow. The single-use fill manifold includes a fill manifold inlet, a plurality of fill manifold outlets, and a fill manifold body conduit. The fill manifold inlet is in fluid communication with each of the plurality of fill manifold outlets via the fill manifold body conduit. The fill manifold inlet is disposed with the pump to deliver a supply fluid to the single-use fill manifold. The fill manifold outlets include at least one standard fill outlet and an underfill outlet. The fill valve apparatus includes a plurality of valves disposed with the single-use fill manifold, such that each of the fill manifold outlets is independently closeable via a corresponding one of the valves of the fill valve apparatus.

[0010] The control unit includes a processor and a non-transitory computer-readable medium having a fluid dispensing program. The processor is configured with the computer-readable medium to execute the fluid dispensing program. The processor is in electronic communication with the pumps and fill valve apparatus to selectively operate the pumps and valves of the fill valve apparatus based on instructions from the fluid dispensing program. The fluid dispensing program has a container filling module configured to deliver a target fill volume of supply fluid from each standard fill outlet of the fill manifold outlets, deliver an underfill volume of supply fluid from the underfill outlet of the fill manifold outlets, and drain the fill manifold volume of supply fluid from the fill manifold body conduit and out of the underfill outlet of the fill manifold outlet. The underfill volume is less than the target fill volume.

[0011] In another aspect, the present disclosure relates to embodiments of techniques for aseptically dispensing fluids. In one embodiment, a method for aseptically dispensing fluids includes supplying a supply fluid to a fill manifold inlet of a single-use fill manifold. A fill portion of the supply fluid is dispensed from all but a reserved one of a plurality of fill manifold outlets of a first single-use fill manifold to a single-use container each aseptically fluidically connected to the fill manifold outlet. After dispensing the fill portion, an underfill portion of the supply fluid is dispensed from the reserved one of the fill manifold outlets to a single-use container aseptically fluidically connected to the fill manifold outlet. The underfill portion is smaller than the fill portion. After dispensing the underfill portion, the fill manifold volume of the supply fluid is drained from a body conduit of the single-use fill manifold out of the reserved one of the fill manifold outlets to a single-use container aseptically fluidically connected to the fill manifold outlet.

[0012]

[0012] Further alternative aspects and features of the disclosed principles will be understood from the following detailed description and the accompanying drawings. As will be understood, the fluid dispensing system and method for aseptically dispensing fluids disclosed herein can be implemented in other different embodiments and can be modified in various respects. It is therefore to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not intended to limit the scope of the appended claims. [Brief explanation of the drawings]

[0013] [Figure 1] 1 is a perspective view of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure in the form of one embodiment of a distributor skid constructed in accordance with the principles of the present disclosure; [Figure 2] FIG. 2 is an elevational view of the distributor skid of FIG. 1. [Figure 3]FIG. 2 is another perspective elevation view of the distributor skid of FIG. 1 and a perspective view of one embodiment of a workstation configured to hold multiple single-use containers for receiving multiple equal portions of fluid from a fluid distribution system. [Figure 4] FIG. 5 is a front view of the distributor skid and workstation of FIG. 4. [Figure 5] 10 is a perspective elevation view of another embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure; and a perspective view of another embodiment of a workstation configured to hold a plurality of single-use containers for receiving equal portions of fluid from the fluid distribution system. [Figure 6] FIG. 6 is a front view of the distributor skid and workstation of FIG. 5. [Figure 7] FIG. 1 is a perspective view of another embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure, including a distributor skid and an embodiment of a distribution tower having a single-use filling manifold of the fluid distribution system attached thereto, and a perspective view of another embodiment of a workstation configured to hold a plurality of single-use containers for receiving multiple equal portions of fluid from the fluid distribution system. [Figure 8] FIG. 8 is a front view of the distributor skid, distribution tower, and workstation of FIG. [Figure 9] FIG. 8 is another front view of the distributor column of FIG. [Figure 10] FIG. 8 is a perspective view of the distribution column of FIG. 7, with the cabinet shown in dashed lines for illustrative purposes. [Figure 11] 10 is a perspective view of another embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure, including the distributor skid of FIG. 7, a distribution tower, and another embodiment of the distribution tower having a single-use filling manifold for the fluid distribution system; and a perspective view of another embodiment of a workstation configured to hold a plurality of single-use containers for receiving multiple equalized portions of fluid from the fluid distribution system. [Figure 12]FIG. 12 is a top view of the distributor skid, distribution tower, and workstation of FIG. 11. [Figure 13] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 14] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 15] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 16] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 17] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 18] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 19] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 20] 1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. [Figure 21]1 is a schematic diagram of one embodiment of a fluid distribution system constructed in accordance with the principles of the present disclosure illustrating a series of fluid recovery steps of one embodiment of a method for sterilely dispensing fluids in accordance with the principles of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0014]

[0026] It should be understood that the drawings are not necessarily to scale, and that the disclosed embodiments are shown diagrammatically and in partial views. In some cases, details that are not necessary for understanding the present disclosure or that make other details difficult to perceive may be omitted. It should be understood that the present disclosure is not limited to the specific embodiments shown herein.

[0015]

[0027] Embodiments of fluid distribution systems constructed in accordance with the principles of the present disclosure are configured for use with embodiments of methods for aseptically dispensing fluids in accordance with the principles of the present disclosure. Embodiments of fluid distribution systems constructed in accordance with the principles of the present disclosure can be used in biopharmaceutical environments and other industrial applications where various fluids, solutions, reagents and / or chemicals are stored in process stations for metering.

[0016]

[0028] For example, embodiments of fluid distribution systems constructed in accordance with the principles of the present disclosure are configured for use in bioprocessing systems, where a feed fluid is distributed to multiple containers for use in bioprocessing applications. Embodiments of fluid distribution systems constructed in accordance with the principles of the present disclosure can be used to perform applications related to bulk filling in pharmaceutical manufacturing. Embodiments of fluid distribution systems constructed in accordance with the principles of the present disclosure can be used to perform applications related to compounding, filling, and other applications related to aseptically aliquoting liquids.

[0017]

[0029] In embodiments, a fluid distribution system includes a scalable series of single-use manifolds in serial fluid communication with one another within a closed sterile system. In embodiments, the fluid distribution system includes two, three, or more single-use manifolds fluidly connected to one another in series, effectively increasing the number of containers that can be aseptically filled through the most upstream single-use manifold to a number greater than the number of outlets present in the system. Thus, the number of containers that can be filled using a fluid distribution system configured according to the principles of the present disclosure is scalable to meet the specific parameters of a given application.

[0018]

[0030] In embodiments, the fluid distribution system includes a single-use distribution manifold configured for sequential sterile fluid connection with a set of single-use fill manifolds corresponding to the number of distribution manifold outlets. In embodiments, each manifold includes a replaceable part that is installed in the fluid distribution system for a single use in a bioprocessing application and removed for disposal after its intended single use. In embodiments, the fluid distribution system includes an upstream single-use distribution manifold configured for sequential sterile fluid connection with a set of intermediate single-use distribution manifolds corresponding to the number of distribution manifold outlets of the upstream single-use distribution manifold. The system also includes a plurality of sets of single-use fill manifolds, each set corresponding to the number of distribution manifold outlets of a corresponding one of the sets of intermediate distribution manifolds.

[0019]

[0031] In an embodiment, the fluid distribution system is incorporated into a distributor skid including at least one single-use distribution manifold and a set of single-use fill manifolds configured to be placed in fluid communication with one of a plurality of distribution manifold outlets. In yet another embodiment, the fluid distribution system is incorporated into the distributor skid and one or more distribution towers, the distribution towers configured to receive one of the sets of single-use fill manifolds.

[0020]

[0032] Embodiments of fluid distribution systems constructed according to the principles of the present disclosure are configured as relatively compact solutions to achieve a scalable range of different fluid distribution solutions for intended use in bioprocessing applications. Embodiments of fluid distribution systems constructed according to the principles of the present disclosure can include a fluid source, at least one single-use distribution manifold, a set of single-use filling manifolds, each having a filling manifold inlet configured to be placed in fluid communication with one of a plurality of distribution manifold outlets and a plurality of filling manifold outlets, and a plurality of containers corresponding to the product of the number of filling manifold outlets and the number of single-use filling manifolds in the set. Multiple sets of containers can be filled using each of the sets of single-use filling manifolds to store fluids therein for use in a given bioprocessing application, with a relatively small footprint (particularly compared to conventional distribution columns configured for use in similar bioprocessing applications). The containers can be delivered to a storage area (e.g., a workstation supporting multiple biocontainer bags for use in a bioprocessing application, such as, for example, a chromatography / tangential flow filtration (TFF) application) as needed. Embodiments of fluid distribution systems constructed according to the principles of the present disclosure can be used as replacements for conventional systems for equivalent bioprocessing applications that use one single-use manifold to fill no more vessels than the number of outlets on the single-use manifold at a time.

[0021]

[0033] Embodiments of a fluid distribution system constructed in accordance with the principles of the present disclosure are configured to drain fluid volume from the body of a single-use fill manifold into a reserved fill container from a set of fill containers, thus forming part of the "usable" customer product fluid. Embodiments of a fluid distribution system constructed in accordance with the principles of the present disclosure are configured to implement a specific automated method in which, after each manifold replacement, fluid from the aforementioned multiplier manifold is fully collected in a collection bag and reintroduced into the system to fill and prime the newly installed manifold. Thus, after a batch is completed (as in the example scenario above), there will be only one "extra" volume in the collection bag (rather than after each separate fill sequence as in the prior art).

[0022]

[0034] An embodiment of a fluid dispensing system constructed according to principles of the present disclosure includes a control unit programmed with a fluid dispensing program having a container filling module configured to deliver a target fill volume of supply fluid from each of the standard fill outlets of the fill manifold outlets, deliver an underfill volume of supply fluid from the underfill outlets of the fill manifold outlets, and drain the fill manifold volume of supply fluid from the fill manifold body conduit and out of the underfill outlets of the fill manifold outlets, where the underfill volume is less than the target fill volume.

[0023]

[0035] In bulk product dispensing applications, air entrapment in both the flow path and the final filled container poses a risk of adversely affecting the process. Air in the flow path can reduce the system's ability to accurately dispense fluid, thereby increasing dispensing variability and adversely affecting downstream formulation processes. Air in the final container can reduce product quality because some products are oxygen sensitive and / or can reduce the efficiency of the process of freezing the fluid in the final container. Embodiments of fluid dispensing systems constructed according to the principles of the present disclosure include a control unit programmed with a fluid dispensing program to automatically remove trapped air in the manifold to increase the accuracy and consistency of the fluid dispensing process.

[0024]

[0036] 1 and 2, there is shown one embodiment of a fluid distribution system 50 constructed in accordance with the principles of the present disclosure incorporated into a distributor skid 52 constructed in accordance with the principles of the present disclosure, including an upstream single-use distribution manifold 53, an intermediate single-use distribution manifold 54, and a single-use fill manifold 55 fluidly connected to one another in series. The distributor skid 52 includes a pump 57 (see FIG. 3) configured to draw fluid from a fluid source (not shown) and deliver the fluid to the serially connected manifolds 53-55.

[0025]

[0037] In the illustrated embodiment, each manifold 53-55 comprises a replaceable part that is installed on distributor skid 52 for use in a bioprocessing application and then removed for disposal. After the intended use in the bioprocessing application is complete, each manifold 53-55 can be removed from distributor skid 52 in a predetermined sequence and replaced with another single-use manifold having a similar structure.

[0026]

[0038] In embodiments, fluid distribution system 50 can be used with any suitable fluid that can be stored in a suitable container, such as a tote, in fluid communication with pump 57. In embodiments, fluid distribution system 50 constructed in accordance with the principles of the present disclosure can include at least two single-use manifolds 54, 55 fluidly connected to each other in series.

[0027]

[0039] The intermediate single-use distribution manifold 54 has substantially the same structure and is one of a set of intermediate single-use distribution manifolds 54 configured to be sequentially mounted to the distributor skid 52. Similarly, the single-use fill manifold 55 has substantially the same structure and is one of a set of single-use fill manifolds 55 configured to be sequentially mounted to the distributor skid 52. The illustrated fluid distribution system 50 is configured to receive fluid from a source (e.g., buffer for use in an intended bioprocessing application, such as chromatography, TFF, etc.) and sequentially distribute the fluid to as many as 120 containers (6 outlets for each of the set of 20 single-use fill manifolds 55 x 5 outlets for each of the set of four intermediate single-use distribution manifolds 54 x 4 outlets of the upstream single-use distribution manifold 53) using the single-use fill manifolds 55 and the set of single-use distribution manifolds 54 sequentially before replacing the upstream single-use distribution manifold 53 to open the closed system.

[0028]

[0040] In other embodiments, fluid distribution system 50 can be configured to fill a different maximum number of containers in a closed system before needing to open to continue dispensing fluid to more containers. In embodiments, a set of intermediate single-use distribution manifolds 54 can include at least one manifold having a different structure (e.g., a different number of outlets) than at least one other manifold in the set, and in embodiments, a set of single-use fill manifolds 55 can include at least one manifold having a different structure (e.g., a different number of outlets) than at least one other manifold in the set.

[0029]

[0041] Referring to FIG. 2, each of the upstream single-use distribution manifold 53, the intermediate single-use distribution manifold 54, and the single-use filling manifold 55 can have a similar structure. In the illustrated embodiment, each manifold 53-55 includes a tubing configuration interconnecting various ports of the manifold and associated control valves for controlling fluid flow through the manifold. In embodiments, the tubing configuration includes multiple flexible tubing lines configured to be selectively closed by externally mounted pinch valves. In embodiments, the flexible tubing can be made of any suitable material, such as silicone, thermoplastic elastomer (TPE), etc.

[0030]

[0042] In embodiments, manifolds 53-55 can be made of any suitable material and can include suitable tubing defining fluid conduits therethrough. In embodiments, manifolds 53-55 include any of a variety of suitable materials and assemblies readily known to those skilled in the art, such as, for example, silicone tubing, plastic injection molded adapters, and commercially available connectors and disconnectors (e.g., Kleenpack® Presto sterile connectors and Kleenpack® sterile disconnectors manufactured by Pall Corporation of New York). The illustrated manifolds 53-55 are made of tubing that can be selectively closed by pinch valves.

[0031]

[0043] An upstream single-use distribution manifold 53 is removably mounted to the distributor skid 52. The upstream single-use distribution manifold 53 has an upstream distribution manifold inlet 60 and a plurality of upstream distribution manifold outlets 61, 62, 63, 64 in fluid communication with the upstream distribution manifold inlet through hollow body conduits in the manifold 53. The illustrated upstream single-use distribution manifold 53 includes four upstream distribution manifold outlets 61-64. In other embodiments, the number of upstream distribution manifold outlets 61-64 may be different. The upstream distribution manifold inlet 60 is fluidly arranged with a pump 57 mounted to the distributor skid 52 for delivering a supply fluid to the series of manifolds 53-55 via appropriate tubing and connectors.

[0032]

[0044] The intermediate single-use distribution manifold 54 is removably mounted to the distributor skid 52. The intermediate single-use distribution manifold 54 has an intermediate distribution manifold inlet 70 and a plurality of intermediate distribution manifold outlets 71, 72, 73, 74, 75 that are in fluid communication with the intermediate distribution manifold inlet 70 through hollow body conduits in the manifold 54. The intermediate distribution manifold inlet 70 is in fluid communication with one of the upstream distribution manifold outlets, in this case the fourth distribution manifold outlet 64. The illustrated intermediate single-use distribution manifold 54 includes five intermediate distribution manifold outlets 71-75. In other embodiments, the number of intermediate distribution manifold outlets 71-75 may be different.

[0033]

[0045] The intermediate single-use distribution manifold 54 is one of a set of intermediate single-use distribution manifolds 54. The set of intermediate single-use distribution manifolds 54 corresponds to the number of upstream distribution manifold outlets 61-64, which in this case is four. Each intermediate single-use distribution manifold 54 has a sterile fluid connector 77 configured to fluidly connect the intermediate distribution manifold inlet 70 to one of the upstream distribution manifold outlets. In embodiments, each intermediate single-use distribution manifold 54 of a set of intermediate single-use distribution manifolds 54 has a similar structure. In embodiments, at least one intermediate single-use distribution manifold 54 of the set of intermediate single-use distribution manifolds 54 can have a different structure from at least one other of the set, such as a different number of intermediate distribution manifold outlets from at least one other of the set of intermediate single-use distribution manifolds 54.

[0034]

[0046] In an embodiment, distribution manifolds 53, 54 are curved, which allows all connecting tubes to be substantially similar in length. This configuration allows both the length and footprint of the manifolds to be kept relatively compact, and also simplifies the manufacturing process for the manifolds.

[0035]

[0047] A single-use fill manifold 55 is removably mounted to the distributor skid 52. The single-use fill manifold 55 has a fill manifold inlet 80 and a plurality of fill manifold outlets 81, 82, 83, 84, 85, 86 that are in fluid communication with the fill manifold inlet 80 through a hollow body conduit of the manifold 55. The fill manifold inlet 80 is in fluid communication with one of the intermediate distribution manifold outlets 71-75, in this case the first intermediate distribution manifold outlet 71. The illustrated single-use fill manifold 55 includes six fill manifold outlets 81-86. In other embodiments, the number of fill manifold outlets 81-86 may be different.

[0036]

[0048] In embodiments, the fill manifold outlets 81-86 include at least one standard fill outlet and an underfill outlet for use with a container fill module of a fluid dispensing program to conserve fluid. In the illustrated embodiment, the single-use fill manifold 55 includes five standard fill outlets 81-85, with the lowest outlet comprising an underfill outlet 86. The container fill module can be configured to deliver a target fill volume of supply fluid from each of the standard fill outlets 81-85 of the fill manifold outlets 81-86, deliver an underfill volume of supply fluid from the underfill outlet 86 of the fill manifold outlets 81-86, and drain the fill manifold volume of supply fluid from the fill manifold body conduit of the single-use fill manifold 55 and out of the underfill outlet 86 of the fill manifold outlets 81-86. The underfill volume is less than the target fill volume. In embodiments, the underfill volume combined with the fill manifold volume is substantially the same as the target fill volume.

[0037]

[0049] The single-use fill manifold 55 is one of a set of single-use fill manifolds 55. In embodiments, the set of single-use fill manifolds 55 corresponds to the product of the number of outlets of each of two or more distribution manifolds connected in series upstream of the fill manifold inlet. In embodiments where only one single-use distribution manifold is connected in series with the fill manifold inlet, the set of single-use fill manifolds 55 can correspond to the number of distribution manifold outlets of the single distribution manifold. In the illustrated embodiment, the set of single-use fill manifolds 55 includes 20 single-use fill manifolds 55, corresponding to the product of the number of intermediate distribution manifold outlets (5) and the number of upstream distribution manifold outlets (4). In embodiments, the set of single-use fill manifolds 55 corresponds to at least the number of intermediate distribution manifold outlets. Each single-use fill manifold has a sterile fluid connector 87 configured to fluidly connect the fill manifold inlet 80 to one of the multiple intermediate distribution manifold outlets 71-75.

[0038]

[0050] In an embodiment, each single-use fill manifold 55 in a set of single-use fill manifolds 55 has a similar structure. In an embodiment, at least one single-use fill manifold 55 in a set of single-use fill manifolds 55 can have a different structure than at least one other single-use fill manifold 55 in the set, such as a different number of fill manifold outlets than at least one other single-use fill manifold 55 in the set.

[0039]

[0051] Referring to FIG. 2, the illustrated fluid distribution system 50 includes a valve 90 associated with each outlet of manifolds 53-55 (only the first of which is shown in FIG. 2). An upstream distribution valve assembly 91 includes a plurality of valves 90 mounted on skid 52 and aligned with the upstream single-use distribution manifold 53, such that each of the upstream distribution manifold outlets 61-64 is independently closable via a corresponding one of the valves 90 of the upstream distribution valve assembly 91. An intermediate distribution valve assembly 92 includes a plurality of valves 90 mounted on skid 52 and aligned with the intermediate single-use distribution manifold 54, such that each of the intermediate distribution manifold outlets 71-75 is independently closable via a corresponding one of the valves 90 of the intermediate distribution valve assembly 92. A fill valve assembly 93 includes a plurality of valves 90 mounted on skid 52 and aligned with the single-use fill manifold 55, such that each of the fill manifold outlets 81-86 is independently closable via a corresponding one of the valves 90 of the fill valve assembly 93.

[0040]

[0052] In embodiments, valve devices 91-93 may include any suitable valve configured to selectively close associated outlets. In the illustrated embodiment, valve devices 91-93 include pinch valves configured to control fluid flow within the system by closing tubing in the manifolds, effectively closing associated manifold outlets. Valve 90 is fixed to skid 52 and provides a means for removably attaching manifolds 53-55 to skid 52. In other embodiments, different types of valves may be used, such as solenoid valves, as would be readily understood by one skilled in the art. In embodiments, valve 90 may be operated by a suitable actuation source, such as, for example, a pneumatic or electrical source. In embodiments, operation of valve 90 in valve devices 91-93 may be coordinated using a suitably programmed control unit to operate one or more desired fluid distribution sequences.

[0041]

[0053] 1, the illustrated distributor skid 52 includes a first fill valve assembly 93 and a second fill valve assembly 94. The first fill valve assembly 93 is located on the side of the distributor skid 52 that includes the upstream and intermediate distribution manifolds 53, 54. The second fill valve assembly 94 is located on another side of the distributor skid 52.

[0042]

[0054] The valves of the first fill valve apparatus 93 are arranged along a vertical axis in spaced apart relationship to one another. The single-use fill manifold 55 is mounted to the distributor skid 52 such that a valve of the first fill valve apparatus 93 is associated with each of the fill manifold outlets. This arrangement is particularly useful for filling containers stored in a workstation 100 configured as shown in FIG. 3.

[0043]

[0055] The valves of the second fill valve apparatus 94 are arranged along a horizontal axis in spaced-apart relationship to one another. A single-use fill manifold 55' as shown in Figure 5 can be mounted to the distributor skid 52 so that a valve of the second fill valve apparatus 94 is associated with each of the fill manifold outlets. This arrangement is particularly useful for filling containers stored in a workstation 100' configured as shown in Figure 5.

[0044]

[0056] 2, in embodiments, the fluid distribution system 50 may include means for removing trapped air within the manifolds 53-55 to increase the accuracy and consistency of the fluid dispensing process. In the illustrated embodiment, an air filter 96 and a vent conduit 97 are provided. The vent conduit 97 is in fluid communication with the manifolds 53-55 via a vent junction 98 associated with the single-use fill manifold 55. The air filter 96 is in fluid communication with the body conduit of the fill manifold 55 and the body conduits of the upstream and intermediate single-use distribution manifolds 53, 54 via the vent conduit 97.

[0045]

[0057] In an embodiment, the air filter 96 is configured to filter out particulates. In an embodiment, the air filter 96 presents a sterile barrier between the product fluid in the manifold and the ambient atmosphere. This essentially prevents non-sterile air from entering the manifold flow path at any time during installation or processing.

[0046]

[0058] The vent conduit 97 includes a vent liquid sensor 99 and a vent valve 101 to protect the air filter 96 from contact with liquid. The vent liquid sensor 99 is configured to generate a liquid detection signal in response to detecting liquid in the vent conduit 97. The control unit 120 is in electrical communication with the vent liquid sensor 99 to receive the liquid detection signal from the vent liquid sensor 99. The vent valve 101 is disposed with the vent conduit 97 to selectively close the vent conduit 97. The vent valve 101 is disposed between the vent liquid sensor 99 and the air filter 96. The vent liquid sensor 99 is disposed between the vent junction 98 and the vent valve 101. The vent valve 101 is operably disposed with the control unit 120 such that the control unit can selectively operate the vent valve 101. In an embodiment, the control unit 120 is configured to stop operation of the pump(s) 57 and / or close the vent valve 101 in response to receiving a liquid detection signal to prevent the filter 96 from becoming wet with fluid during priming of the distribution manifold.

[0047]

[0059] In an embodiment, the control unit 120 is configured to perform a priming operation. In an embodiment, the control unit 120 is configured to, with all of the fill manifold outlets 81-86 closed, open the vent valve 101 to open the vent conduit 97, and operate the pump(s) 57 to deliver a flow of fluid to the single-use fill manifold 55, thereby filling the body of the fill manifold 55 with fluid and expelling air within the manifolds 53-55 through the vent junction 98 and into the vent conduit 97. The control unit 120 can be configured to stop operation of the pump(s) 57 and / or close the vent valve 101 in response to receiving a liquid detection signal indicating that the body of the single-use fill manifold 55 is filled with fluid above the vent junction 98.

[0048]

[0060] In embodiments, the vent junction 98 is positioned at an elevated position relative to the series of manifolds 53-55 fluidly connected to one another. In embodiments, the distribution manifolds 53, 54 are configured such that fluid travels from the upstream distribution manifold inlet 60 to the fill manifold inlet 80, and, in embodiments, to the vent junction 98, in a substantially upward trajectory toward the fill manifold 55. In embodiments, the bodies of the distribution manifolds 53, 54 extend along a line of an inclined path that is at least 0.5° relative to a horizontal axis. The control unit 120 can be configured such that, during a priming operation, when liquid is taken into the upstream distribution manifold inlet 60 and flows through the manifolds 53-55, the liquid displaces air in the current flow path, forcing the air out of the series of manifolds 53-55 and into the air filter 96.

[0049]

[0061] In an embodiment, the control unit 120 is configured to perform an underfill operation. In an embodiment, the control unit 120 is configured to supply a supply fluid to the fill manifold inlet 80 of the single-use fill manifold 55 and sequentially dispense target fill volumes of fluid from each of the standard fill outlets 81-85 of the single-use fill manifold 55 into single-use containers that are aseptically fluidically connected to the standard fill outlets. After the target fill volumes are dispensed sequentially, an underfill volume of fluid is dispensed from the underfill outlet 86 of the single-use fill manifold 55 into the single-use containers that are aseptically fluidically connected to the underfill outlet 86. In an embodiment, the underfill volume is smaller than the target fill volume. In an embodiment, the volume of fluid drained from the fill manifold 55 combined with the underfill volume is substantially equal to the target fill volume. In an embodiment, the underfill outlet 86 of the single-use fill manifold 55 may be the lowest outlet in the direction in which gravity acts.

[0050]

[0062] After delivering the underfill volume, the control unit 120 can be configured to drain the fluid from the body conduit of the fill manifold 55 through the underfill outlet 86 to a single-use container that is sterilely fluidly connected to the underfill outlet 86. The control unit 120 can be configured to open the vent valve 101 during the draining.

[0051]

[0063] In embodiments, a fill manifold drain valve 102 may be provided upstream of vent junction 98 to selectively close fill manifold inlet 80 during a fill manifold drain operation to further facilitate draining of fluid from the body of fill manifold 55 to underfill outlet 86. Fill manifold drain valve 102 is operatively disposed with control unit 120 such that the control unit can selectively operate fill manifold drain valve 102. In embodiments, control unit 120 is configured to close fill manifold drain valve 102 during fill manifold drain to help maintain consistency in the volume of fluid drained from fill manifold 55 during a drain operation.

[0052]

[0064] In an embodiment, a drain liquid lower limit sensor 103 may be associated with the body of the fill manifold 55 near and above the underfill outlet 86 so as to monitor the fluid level within the body of the fill manifold 55 to help determine when the drain operation of the fill manifold is complete. The drain liquid lower limit sensor 103 is configured to generate a fill manifold drain liquid lower limit signal in response to detecting that the liquid within the fill manifold 55 is below a predetermined low level, which corresponds to the drain operation being complete / nearly complete.

[0053]

[0065] The control unit 120 is in electrical communication with the drain liquid lower limit sensor 103 to receive the fill manifold drain liquid lower limit signal. In embodiments, the control unit 120 can be configured to stop the draining operation of the fill manifold in response to receiving the fill manifold drain liquid lower limit signal. In embodiments, the control unit 120 can be configured to open the fill manifold drain valve 102 and close the vent valve 101 in response to receiving the fill manifold drain liquid lower limit signal. The location of the drain liquid lower limit sensor 103 also helps ensure that the draining operation of the fill manifold stops before all fluid has drained from the fill manifold 55, preventing air from being delivered to a single-use container connected to the underfill outlet 86.

[0054]

[0066] In embodiments, the fluid distribution system 50 may include means for withdrawing fluid from one or more of the manifolds 53-55 that would otherwise be retained within the manifolds 53-55 or not delivered into the single-use containers being filled during the filling operation. In the illustrated embodiment, the fluid distribution system 50 includes means for withdrawing fluid from one or more of the distribution manifolds 53, 54, comprising a withdrawal conduit 106, a withdrawal container 107, and a withdrawal pump 108.

[0055]

[0067] The recovery conduit 106 is in fluid communication with the distribution manifolds 53, 54 and comprises a sterile fluid reserve path configured to be disposed in fluid communication with a recovery container 107 (see also FIG. 1 ). The recovery conduit 106 comprises a recovery valve 109. The recovery valve 109 is disposed with the sterile valve reserve path 106 such that the sterile fluid reserve path 106 is closeable via the recovery valve 109. The recovery valve 109 is disposed operatively with the control unit 120 such that the control unit 120 can selectively operate the recovery valve 109.

[0056]

[0068] The collection receptacle 107 can be placed in fluid communication with the distribution manifold(s) 53, 54 via a sterile fluid pre-path provided by the collection conduit 106. The collection receptacle storage compartment 116 is attached to the distributor skid 52 (see also FIG. 1 ). The collection receptacle storage compartment 116 is configured to house the collection receptacle 107 therein. The collection receptacle storage compartment 116 is positioned such that the collection receptacle 107 is positioned downward in the direction in which gravity acts on the fluid in the distribution manifolds 53, 54, the distribution manifolds 53, 54, and the air filter 96.

[0057]

[0069] A recovered liquid upper limit sensor 117 and a recovered liquid lower limit sensor 118 can be associated with the storage compartment 116 to monitor predetermined maximum and minimum fluid volumes in the collection container (see also FIG. 13 ) to help avoid overfilling the collection container and / or inadvertently drawing air into the system. Referring to FIG. 13 , the recovered liquid upper limit sensor 117 is disposed with the collection container 107 and is configured to generate a recovered liquid upper limit signal in response to detecting that the liquid in the collection container 107 is at a predetermined high level corresponding to the predetermined maximum fluid volume in the collection container. The recovered liquid lower limit sensor 116 is disposed with the collection container 107 and is configured to generate a recovered liquid lower limit signal in response to detecting that the liquid in the collection container 107 has fallen below a predetermined low level corresponding to the predetermined minimum fluid volume in the collection container. The control unit 120 is in electrical communication with the recovered liquid upper and lower limit sensors 117, 118 to receive recovered liquid upper and lower limit signals from the recovered liquid upper and lower limit sensors 117, 118, respectively.

[0058]

[0070] 2, in an embodiment, recovery pump 108 is in fluid communication with recovery vessel 107 via recovery conduit 106 and fluid supply conduit 119, which are fluidly connected to upstream distribution manifold inlet 60. The recovery pump is configured to selectively generate a flow of recovery fluid from the recovery vessel to upstream distribution manifold inlet 60 to form part of the supply fluid distributed through manifolds 53-55.

[0059]

[0071] In embodiments, the control unit 120 can be configured to automatically drain fluid from the distribution manifolds 53, 54 through the recovery conduit 106 and into the collection container 107. In embodiments, the control unit 120 is configured to open the vent valve 101 to admit air from outside the air filter 96 into the distribution manifolds 54, 53 and open the recovery valve 109. In embodiments, the control unit 120 can be configured to close the vent valve 101 and close the recovery valve 109 in response to receiving a recovered liquid high limit signal and stopping the distribution manifold draining operation. In embodiments, a recovered liquid sensor can be provided in the recovery conduit 106 upstream of the collection container 107 to provide a signal to the control unit when the recovery level sensor detects that no more fluid is passing through the recovery conduit 106 to the collection container 107, thereby allowing the control unit 120 to stop the distribution manifold draining operation.

[0060]

[0072] In embodiments, the control unit 120 can be configured to automatically re-draw fluid from the collection container 107 into the series of manifolds 53-55 during a priming operation. In embodiments, the control unit 120 can be configured to operate the collection pump 108 to draw recovered fluid from the collection container 107 into the upstream distribution manifold inlet 60. In embodiments, the control unit 120 can be configured to supply feed fluid to the upstream distribution manifold inlet 60 by drawing recovered fluid from the collection container 107 such that at least a portion of the feed fluid is composed of recovered fluid from the collection container 107. In embodiments, the control unit 120 can be configured to operate the collection pump 108 and at least one other pump 57 during a priming operation. In embodiments, the control unit 120 can be configured to stop operation of the collection pump 108 during a fluid priming operation in response to receiving a low recovered liquid limit signal.

[0061]

[0073] 1, distributor skid 52 includes trolley 105, cabinet 110, single-use manifolds 53-55, and valve assemblies 91-94. Cabinet 110 is mounted on trolley 105 and configured to house the hydraulic automation equipment of liquid distribution system 50. Manifolds 53-55 include single-use manifolds removably mounted to cabinet 110, and manifolds 53-55 are operably arranged with the valves of valve assemblies 91-93 mounted to cabinet 110.

[0062]

[0074] The trolley 105 includes a base 112 and a plurality of wheels 114 rotatably mounted to the base 112. In the illustrated embodiment, the base 112 is rectangular with a wheel 114 rotatably mounted at each corner of the base 112. In an embodiment, the base 112 may be substantially square.

[0063]

[0075] Cabinet 110 is mounted to base 112 of trolley 105. In an embodiment, cabinet 110 comprises a storage unit for automated hydraulic equipment and is fabricated from a suitable metal, such as stainless steel. Cabinet 110 defines an interior cavity that may be suitably configured to store and support components of a liquid dispensing system. Valves of valve assemblies 91-94 may be supported by cabinet 110. In the illustrated embodiment, a clamping portion of each valve protrudes from an exterior surface of cabinet 110 so as to be associated with a respective manifold outlet.

[0064]

[0076] Referring to FIG. 3 , in an embodiment, cabinet 110 houses control unit 120 and at least one pump body 57 therein. Pump 57 is in operative relationship with control unit 120 such that control unit 120 can selectively operate pump 57. Pump 57 is configured to selectively generate a fluid flow for delivery of a supply fluid to manifolds 53-55. In an embodiment, pump 57 may be any suitable pump capable of generating a fluid flow through manifold 53 for delivery to single-use containers 125 connected to fill manifold 55 and meeting the specifications of the intended application. In an embodiment, pump 57 includes a variable displacement pump. In an embodiment, fluid distribution system 50 includes multiple pumps that can be used to deliver one or more types of fluid to manifolds 53-55.

[0065]

[0077] In embodiments, control unit 120 may include any suitable equipment configured to control the operation of at least one component of liquid dispensing system 50 when performing a fill operation. In embodiments, control unit 120 includes a processor 121, a non-transitory computer-readable medium 122 having a fluid dispensing program, a data storage device 123, and a display device 125. Processor 121 is configured with computer-readable medium 122 to execute the fluid dispensing program. Processor 121 is operably configured with display device 125 to selectively display output information from the fluid dispensing program and / or receive input information from a graphical user interface displayed by display device 125.

[0066]

[0078] The processor 121 can be configured to function as a controller for selectively operating at least one component of the fluid distribution system 50, such as, for example, the pump 57 and the valve arrangement. In an embodiment, the processor 121 is in electronic communication with the pump(s) and the valve arrangement to selectively operate the valves based on instructions from a fluid distribution program.

[0067]

[0079] In embodiments, the controller and processor 121 may comprise separate devices, or the controller may be disposed in operative communication with the processor 121. In embodiments, the controller may include a user input and / or interface device having one or more user-actuated mechanisms (e.g., one or more push buttons, slide bars, rotatable knobs, keyboards, and mice) configured to generate one or more user-actuated input control signals. In embodiments, the controller may be configured to include one or more other user-actuated mechanisms for providing various other control functions for the fluid dispensing system, as will be appreciated by those skilled in the art. The controller may be associated with a display device 125 configured to display a graphical user interface. The graphical user interface, in embodiments, may be configured to function as both a user input device and a display device. In embodiments, the display device 125 may include a touchscreen device configured to receive input signals from a user touching various portions of the display screen. In embodiments, the controller may be in the form of a smartphone, tablet, personal digital assistant (e.g., wireless mobile device), laptop computer, desktop computer, or other type of device.

[0068]

[0080] In embodiments, the fluid distribution program includes a scaling module configured to sequence through a series of valve opening and closing states to execute a fill sequence according to the principles of the present disclosure. For example, the scaling module can be configured to open a corresponding one of the upstream and intermediate distribution manifold outlets and close the other of the upstream and intermediate distribution manifold outlets to perform a corresponding series of consecutive fill operations using a corresponding one of the set of single-use fill manifolds. The scaling module sequentially opens each of the intermediate distribution manifold outlets while leaving one of the upstream distribution manifold outlets open, then closes that one of the upstream distribution manifold outlets, opens a second of the upstream distribution manifold outlets, and closes the others. The scaling module can sequentially adjust the fill operations of the remaining valves in a similar manner. In embodiments, the scaling module includes logic to scale the fill operations to a desired number of containers for a given closed system fill sequence.

[0069]

[0081] In embodiments, the fluid dispensing program is configured to perform at least one fluid recovery operation to efficiently use fluid that would otherwise be held within the manifolds 53-55 or not delivered into the single-use containers being filled during the fill operation. In embodiments, the fluid dispensing program is configured to perform at least one of the fluid recovery operations in the form of an underfill operation of the single-use container, a drain operation of the manifold, and a prime operation of the manifold.

[0070]

[0082] For example, in an embodiment, the fluid dispensing program includes a container fill module configured to automatically perform at least one fluid recovery operation. In an embodiment, the fluid dispensing program includes a container fill module configured to perform a fluid recovery operation in the form of an underfill operation for a single-use container. In an embodiment, the container fill module is configured to perform an underfill operation for a single-use container, including delivering a target fill volume of supply fluid from each of the standard fill outlets 81-85 of the fill manifold outlets 81-86, delivering an underfill volume of supply fluid from an underfill outlet 86 of the fill manifold outlets 81-86, and draining the fill manifold volume of supply fluid from a fill manifold body conduit of the single-use fill manifold 55 and out of the underfill outlet 86 of the fill manifold outlets 81-86. The underfill volume is less than the target fill volume. In an embodiment, the underfill volume combined with the fill manifold volume is substantially the same as the target fill volume.

[0071]

[0083] In embodiments, the container filling module is configured to perform a single-use container underfill operation, including supplying a supply fluid to the fill manifold inlet 80 of the single-use fill manifold 55. A target fill volume of fluid is sequentially delivered from each of the standard fill outlets 81-85 of the fill manifold outlets 81-86 to a single-use container that is aseptically fluidically connected to the standard fill outlet. After the target fill volumes are sequentially delivered, an underfill volume of fluid is delivered from the underfill outlet 86 to a single-use container that is aseptically fluidically connected to the underfill outlet. After the underfill volume is delivered, the fill manifold volume of fluid is drained from the fill manifold body conduit 55, out of the underfill outlet 86, to a single-use container that is aseptically fluidically connected to the underfill outlet 86. In some embodiments, the underfill portion and the fill manifold volume are combined to be substantially the same as the fill portion. In embodiments, the vent valve 101 is open during draining to facilitate draining of the fluid from the body conduit of the fill manifold 55. In an embodiment, the container filling module is configured to deliver multiple filling portions substantially simultaneously.

[0072]

[0084] In embodiments, the fluid distribution program is configured to perform a fluid recovery operation in the form of a manifold drain operation. In embodiments, the fluid distribution program, when executed by the processor, includes a distribution manifold drain module configured to drain fluid from at least one distribution manifold 53, 54 to a sterile fluid reserve path 106 to a recovery container 107. In embodiments, draining the fluid from the distribution manifolds includes draining fluid remaining in both the upstream single-use distribution manifold 53 and the intermediate single-use distribution manifold 54. In embodiments, draining the fluid from the distribution manifolds includes opening the vent valve 101 and opening at least one recovery valve 109 disposed with the recovery conduit 106. In embodiments, the distribution manifold drain module, when executed by the processor, is configured to close the vent valve 101 and close the recovery valve 109 disposed with the recovery conduit 106 in response to receiving a recovered liquid high limit signal.

[0073]

[0085] In embodiments, the fluid dispensing program is configured to perform a fluid withdrawal operation in the form of a manifold priming operation. In embodiments, the fluid dispensing program includes a fill manifold priming module configured to perform a fluid withdrawal operation in the form of a manifold priming operation. In embodiments, the fluid dispensing program includes a fill manifold priming module configured to prime a fill manifold body conduit of the single-use fill manifold with a supply fluid that fills the body of the fill manifold. In embodiments, the fill manifold priming module is configured to open vent valve 101 to expel air in the fill manifold body conduit out through air filter 96 during priming, and to close vent valve 101 after the fill manifold body is primed.

[0074]

[0086] In embodiments, the fill manifold priming module is configured to prime the manifold(s) by introducing recovered fluid from the recovery container 107 via the sterile fluid prep path 106 into the distribution manifold inlet 60, such that at least a portion of the supply fluid consists of recovered fluid from the recovery container 107. In embodiments, the fill manifold priming module is configured to operate the recovery pump 108 to draw recovered fluid from the recovery container 107 during the manifold priming operation. In embodiments, the fill manifold priming module is configured to stop operation of the recovery pump and close a recovery valve disposed with the recovery fluid fill path 106 in response to receiving a recovered liquid low limit signal.

[0075]

[0087] In an embodiment, a control unit 120 is in electrical communication with each pump 57, 107 and each valve in the valve arrangements 91-94 used to deliver fluid to the manifolds 53-55. The control unit 120 is configured to selectively operate the pump 57 and the valves in the valve arrangements 91-94 according to logic and operational parameters contained in a fluid dispensing program. In an embodiment, the control unit 120 is configured to control at least one of the pumping speed and output volume of the pump 57 to control the amount of fluid dispensed into the single-use containers 125 connected to the fill manifold 55. In the illustrated embodiment, the control unit 120 is configured to independently operate each valve in the various valve arrangements 91-93 to place each valve arrangement in a series of sequential valve states to fill a number of single-use containers 125 greater than the number of fill manifold outlets in any one of the set of single-use fill manifolds 55.

[0076]

[0088] In an embodiment, the control unit 120 is configured to selectively operate the pump(s) 57 according to at least one input signal received from each workstation 100 holding a container 125. In an embodiment, the control unit 120 is configured to operate the distributor skid 52 to perform at least one fill sequence.

[0077]

[0089] In embodiments, processor 121 comprises a specially programmed processor that can be used to fill a series of single-use containers 125 using at least one distribution manifold 53, 54 and a set of single-use fill manifolds 55. In the illustrated embodiment, processor 121 is configured to facilitate control and operation of fluid distribution system 50. In embodiments, processor 121 can be configured to receive input signals from a controller, send input control signals to the controller, and / or send output information to the controller. In the illustrated embodiment, the controller and processor 121 comprise the same device.

[0078]

[0090] In an embodiment, the processor 121 is configured to display fluid data received from at least one sensor in electrical communication with the control unit 121 on a display device 125. The fluid data may also be stored in a data storage device 123 operatively arranged with the processor 121.

[0079]

[0091] In an embodiment, processor 121 may include any suitable computing device, such as a microprocessor, a mainframe computer, a digital signal processor, a portable computing device, a personal organizer, a device controller, a logic device (e.g., a programmable logic device configured to perform processing functions), a digital signal processing (DSP) device, or a computational engine within an appliance, etc. In an embodiment, processor 121 also includes one or more additional input devices (e.g., a keyboard and a mouse).

[0080]

[0092] Processor 121 may have one or more associated memory devices for storing data and information. The one or more memory devices may be of any suitable type, including volatile and non-volatile memory devices such as RAM (random access memory), ROM (read only memory), EEPROM (electrically erasable programmable read only memory), flash memory, etc. In one embodiment, processor 121 is configured to execute programming stored on non-transitory computer-readable medium 122 to implement various methods, processes, and modes of operation in a manner consistent with the principles of the present disclosure.

[0081]

[0093] In an embodiment, the non-transitory computer-readable medium 122 may include a fluid dispensing program configured to implement an embodiment of a method for dispensing fluid according to the principles of the present disclosure. In an embodiment, the fluid dispensing program includes a graphical user interface that may be displayed by the display device 125. The graphical user interface may be used to facilitate the input of commands and data by a user into the fluid dispensing program and to display output generated by the fluid dispensing program.

[0082]

[0094] The fluid dispensing program may be stored on any suitable computer-readable storage medium. For example, in embodiments, a fluid dispensing program according to the principles of the present disclosure may be stored on a hard drive, floppy disk, CD-ROM drive, tape drive, ZIP drive, flash drive, optical storage device, magnetic storage device, etc.

[0083]

[0095] In an embodiment, the processor 121 is in operative communication with a data store 123, which includes at least one database containing fluid dispensing data. In an embodiment, the fluid dispensing program may be configured to store fluid dispensing data generated during operation of the system in the data store 123. In an embodiment, the fluid dispensing data may be logically associated with time data in the data store such that various data can be searched over a given time period.

[0084]

[0096] 4, workstation 100 is configured to hold a plurality of single-use containers 125. Each single-use container 125 has an access port 130 that is fluidly connected to a corresponding one of fill manifold outlets 81-86 via a sterile fluid disconnector 131 and a sterile fluid connector 132.

[0085]

[0097] Workstation 100 comprises a workstation configured to hold fluid aliquots from a larger supply by a fluid dispensing system in single-use containers 125. Workstation 100 includes a trolley 140, a frame structure 143, a collection container storage compartment 144, and a scale 145.

[0086]

[0098] The frame structure 143 is attached to the trolley 140 and is configured to support stacked single-use containers 125. The frame structure 143 includes four spaced-apart uprights 147 connected to each corner of the trolley 140 and four cross members 148, each extending between two of the uprights 147, such that the frame structure 143 has a rectangular configuration. In the illustrated embodiment, the workstation includes six shelves 149, each configured to support at least one single-use container 125, such that the frame structure 143 can support single-use containers 125 stacked vertically on top of each other. In other embodiments, the workstation 100 can be configured to support a different number of single-use containers 125, including having shelves 149, each configured to support multiple single-use containers 125.

[0087]

[0099] The collection receptacle storage compartment 144 is attached to the frame structure 143 and configured to receive the collection receptacle 107 therein. In an embodiment, upon opening the closed system after performing a scaled fill operation using the serially connected manifolds 53-55, the collection receptacle 107 may be removed from the collection conduit 106 and stored in the collection receptacle storage compartment 144 attached to the frame structure 143. Any "leftover" volume of fluid remaining in the collection receptacle 107 may be associated with the single-use containers filled during use of this particular collection receptacle 107. Rather than generating leftover volume during a fill operation performed using each one of the set of single-use fill manifolds 55, the collection receptacle 107 may be the only leftover volume generated after using all of the set of fill manifolds 55.

[0088]

[0100] The trolley 140 includes a base and a plurality of wheels rotatably mounted to the base. In the illustrated embodiment, the base is rectangular with a wheel rotatably mounted at each corner of the base. In an embodiment, the base may be substantially square. The base of the trolley 140 is attached to the bottom of a frame structure 143. The trolley 140 can be positioned on a scale 145 such that the scale 145 supports the weight of the trolley 140 (and the frame structure 143 and the container 125 stored therein).

[0089]

[0101] In embodiments, scale 145 may be any suitable scale suitable for weighing loads within a range corresponding to the intended fluid application. In embodiments, scale 145 comprises a suitable load cell that generates an electrical signal indicative of a measured weight. Scale 145 may be configured to generate a weight signal and may be disposed in electrical communication with control unit 120 for transmitting the weight signal to control unit 120. Control unit 120 may use the weight signal to provide a feedback loop to control unit 120 to confirm that the intended amount of fluid has been dispensed into container 125 stored in workstation 100. In embodiments, control unit 120 may be configured to convert the measured weight of fluid into a volume measurement of the fluid.

[0090]

[0102] In other embodiments, a workstation suitable for use with a fluid dispensing system constructed according to the principles of the present disclosure may have a different configuration. For example, in other embodiments, the volume / weight of the container 125 may be monitored using other technologies, such as fill level sensors, as will be understood by those skilled in the art. In embodiments, the fill level sensors are configured to generate a fill level signal indicative of the amount of material in the storage volume of the single-use container detected by the fill level sensor. Each fill level sensor may be positioned in electrical communication with a control unit such that the control unit can use the fill level signal as a feedback loop. In embodiments, a fill level capacitance sensor may be used to measure the fill level of a fluid medium or solid material disposed in the storage volume of the container. In embodiments, the fill level capacitance sensor may be a suitable commercially available strip sensor, such as one available from Balluff Ltd., capable of detecting the fill level along a strip spanning a predetermined length, such as 850 mm. In embodiments, the fill level capacitance sensor for measuring the fill level may be configured to generate a measurement impedance in response to being within proximity of detection of the material stored in the single-use container, the ohmic component of which, in particular the capacitive component, reflects the measurement of the fill level of the material in the container and may be used to generate the fill level signal.

[0091]

[0103] Each of the single-use containers 125 is fluidly connected to a corresponding one of the fill manifold outlets 81-86 of the distributor skid 52 via a flexible tubing line extending between each container 125 and its associated fill manifold outlet 81-86, with fluid communication selectively maintained via a respective sterile connector 132. In embodiments, the sterile connectors 132 may be any suitable connector, such as commercially available sterile connectors familiar to those skilled in the art. In embodiments, the tubing placing the containers 125 in fluid communication with the associated fill manifold outlets 81-86 is configured to be selectively closed by a pinch valve attached to its exterior, and in embodiments comprises flexible tubing made of any suitable material, such as silicone, thermoplastic elastomer (TPE), etc.

[0092]

[0104] In embodiments, single-use container 125 includes any suitable container configured to store a predetermined volume of material for use in an intended application. In embodiments, single-use container 125 includes a "2D" (or "two-dimensional") biocontainer bag, as is well known to those skilled in the art.

[0093]

[0105] In the illustrated embodiment, the single-use vessel 125 comprises a 2D biocontainer bag made of a flexible film material. The biocontainer bag 125 can include two or more ports and tubing with connector ends configured to receive materials within the bag's interior storage volume and / or deliver materials from the bag. In other embodiments, the biocontainer bag 125 includes at least one other port configured for use as a sampling port. In embodiments, the biocontainer bag 125 can define a predetermined amount of storage volume therein, such as, for example, a volume ranging from 1 liter to 20 liters. In other embodiments, the storage volume can be a different amount, such as, for example, 100 liters. In embodiments, the biocontainer bag 125 comprises a suitable commercially available single-use biocontainer bag, such as, for example, one available under the trade name "Allegro™ 2D Biocontainer Bag" from Pall Corporation of Port Washington, New York.

[0094]

[0106] In embodiments, the biocontainer bag 125 can include at least one pair of flexible panels connected to one another. The flexible panels cooperate to define an interior storage volume configured to hold a predetermined amount of material (e.g., 100 liters). In embodiments, each panel is made of a suitable plastic material. For example, in embodiments, each panel is made of a fluid-contacting portion made of low-density polyethylene (LDPE) and an outer film having a gas-barrier inner film made of ethylene-vinyl alcohol copolymer (EvOH). In embodiments, the biocontainer bag can be made of a material that meets at least one of the following requirements: Targeted monitoring of the effects of the biocontainer extract for its systemic toxicity, tissue irritation, and biocompatibility for implantation; USP <88> In vivo biological reactivity testing of Class VI-50°C plastics; USP <87> Biological reactivity tests (in vitro) for plastics (cytotoxicity); ISO 10993 Biological Evaluation of Medical Devices (Section 8.2.2: ISO 10993 Biological Evaluation of Medical Devices), Section 4 (hemolysis), Section 5 (cytotoxicity), Section 6 (implantation tests), Section 10 (irritation and sensitization tests), and Section 11 (acute systemic toxicity).

[0095]

[0107] Referring to FIG. 5, in an embodiment, fluid distribution system 50' includes a single-use fill manifold 55' mounted on distributor skid 52 such that a valve of second fill valve apparatus 94 is associated with each of fill manifold outlets 81', 82', 83', 84', 85', and 86', respectively. The valves of second fill valve apparatus 94 are arranged in spaced-apart relation to one another along a horizontal axis. This arrangement allows fill manifold outlets 81'-86' to be aligned on a workstation 100' configured as shown in FIGS. 5 and 6.

[0096]

[0108] The workstation 100′ shown in FIGS. 5 and 6 includes a trolley 140, a frame structure 143′, and a scale 145. The frame structure 143′ is attached to the trolley 140 and configured to support one or more biocontainer totes. The frame structure 143′ includes an upright structure configured to hold the totes in place and form a pair of handle portions 152 suitable for grasping when moving the workstation 100′ over a surface on which the wheels of the trolley 140 rest. The workstation 100′ comprises a workstation configured to hold aliquots of fluid from a larger source into at least one single-use tote by a fluid distribution system 50′. The workstation 100′ of FIG. 5 may be similar to the workstation 100 of FIG. 3 in other respects.

[0097]

[0109] 7-10 , in an embodiment, a fluid distribution system 250 constructed according to the principles of the present disclosure includes at least one single-use fill manifold 255 and at least one fill valve apparatus 293 mounted to a distribution tower 295 separate from a distributor skid 252. The illustrated distribution tower 295 comprises a trolley 305 and a packed tower 310. The packed tower 310 extends from the trolley 305. In the embodiment shown in FIGS. 7 and 8 , two of the set of single-use fill manifolds, 255, 255′, are mounted to the packed tower of the distribution tower. In an embodiment, a fill valve apparatus 293 is mounted to the tower 310 and can be associated with one of the single-use fill manifolds 255 mounted to the packed tower 310, with a valve of the fill valve apparatus 293 associated with a respective one of the fill manifold outlets. The fill manifold outlets of this single-use fill manifold 255 may be placed in fluid communication with a corresponding plurality of single-use containers, which may be supported by the workstations 300, 301, respectively.

[0098]

[0110] In an embodiment, after a first of the single-use filling manifolds 255 attached to the packed tower 310 has been used in a filling operation, another of the single-use filling manifolds 255′ attached to the packed tower 310 can be associated with the filling valve apparatus 293 attached to the packed tower 310 and with another of the intermediate distribution manifold outlets of the intermediate single-use distribution manifold 254. The other of the single-use filling manifolds 255′ attached to the packed tower 310 can then be used in a second filling operation with another set of single-use containers.

[0099]

[0111] 9 and 10, a packed column 310 of a distribution column 295 is shown with a packing valve apparatus 293 and one single-use packing manifold 255 attached thereto. The packed column 310 includes an enclosure 315 capable of supporting multiple valves, including the packing valve apparatus 293, such that the clamping portions of the valves extend from the exterior surface of the enclosure 315. The clamping portions 297 can be associated with corresponding ones of the packing manifold outlets 281 (only one of which is shown), as shown in FIG.

[0100]

[0112] 11 and 12, in an embodiment, a fluid distribution system 450 constructed in accordance with the principles of the present disclosure includes at least one single-use fill manifold 455 and at least one fill valve apparatus 493 mounted to a distribution tower 497 separate from a distributor skid 452. In the embodiment shown in FIGS. 11 and 12, a pair of distribution towers 495, 497 are provided. In an embodiment, the fluid distribution system 450 includes multiple distribution towers configured to support multiple different single-use containers filled through the fluid distribution system.

[0101]

[0113] In the illustrated embodiment, one distribution tower 495 is similar in construction to distribution tower 295 of Figures 7-10. The other distribution tower 497 includes a gantry 505 including first and second uprights 507, 508 and a beam 509 extending between the upper ends of the first and second uprights 507, 508. Each upright 507, 508 includes a trolley at its base and is configured to facilitate mobility of gantry 505. A set of single-use fill manifolds 455 and one of fill valve apparatus 493 are mounted on the beam.

[0102]

[0114] 11, in an embodiment, the fill manifold inlet of this single-use fill manifold can be placed in fluid communication with one of the intermediate distribution manifold outlets of a single-use intermediate distribution manifold 454 mounted on a distributor skid 452. The fill manifold outlets of this single-use fill manifold 455 can be placed in fluid communication with a corresponding plurality of single-use containers, each of which can be supported by a workstation 500, 501.

[0103]

[0115] In an embodiment, a fill manifold inlet of a single-use fill manifold 456 mounted on the packed tower 510 can be placed in fluid communication with another of the intermediate distribution manifold outlets of a single-use intermediate distribution manifold 454 mounted on the distributor skid 452. The fill manifold outlets of this single-use fill manifold 456 can be placed in fluid communication with a respective different set of single-use vessels that can be supported by the workstations 500, 501, or other differently configured workstations, such as those shown in FIG.

[0104]

[0116] In other embodiments, a fluid distribution system constructed in accordance with the principles of the present disclosure can include various devices configured to hold a supply fluid for delivery to a manifold for distributed, scaled dispensing in a plurality of single-use containers. For example, in other embodiments, a fluid distribution system constructed in accordance with the principles of the present disclosure can include at least one tower configured to hold one or more totes filled with fluid for use with the fluid distribution system. In other embodiments, a fluid distribution system constructed in accordance with the principles of the present disclosure can include one or more tanks filled with fluid for use in the system.

[0105]

[0117] In other embodiments of fluid distribution systems constructed according to the principles of the present disclosure, the fluid distribution system configuration can take alternative forms. For example, in embodiments, the distribution column can be replaced by a tote. In other embodiments, the fluid distribution system can be scaled to a larger capacity or reduced in size for laboratory use. In embodiments, the fluid distribution system can include a single-use manifold constructed from a rigid plastic structure. In embodiments, a fluid distribution system constructed according to the principles of the present disclosure can be used to process a variety of liquids to meet the requirements of a desired application.

[0106]

[0118] In an embodiment of a method of using a fluid distribution system in accordance with the principles of the present disclosure, a fluid distribution system configured in accordance with the principles of the present disclosure is used to deliver multiple portions of a fluid to a series of single-use containers as described herein. In an embodiment, the method of using a fluid distribution system in accordance with the principles of the present disclosure can be used with any embodiment of a fluid distribution system in accordance with the principles described herein, including an embodiment of a distributor skid having at least one single-use distribution manifold in accordance with the principles of the present disclosure.

[0107]

[0119] In one embodiment, a method for aseptically dispensing a fluid includes supplying a fluid to a distribution manifold inlet of a single-use distribution manifold. A first supply fluid is delivered from a first distribution manifold outlet port of a plurality of distribution manifold outlet ports of the single-use distribution manifold through a first sterile fluid pathway to a fill manifold inlet of a first single-use fill manifold. A plurality of portions of the first supply fluid are delivered from the plurality of fill manifold outlet ports of the first single-use fill manifold to corresponding ones of a first set of single-use containers each aseptically fluidly connected to the plurality of fill manifold outlet ports of the first single-use fill manifold. After the plurality of portions of the first supply fluid are delivered, the first single-use fill manifold is detached from the single-use distribution manifold.

[0108]

[0120] The second supply fluid is delivered from a second outlet port of the plurality of distribution manifold outlet ports of the single-use distribution manifold via a second sterile fluid pathway to a fill manifold inlet of the second single-use fill manifold, and portions of the second supply fluid are delivered from each of the plurality of fill manifold outlet ports of the second single-use fill manifold to a corresponding one of a second set of single-use containers each sterilely fluidly connected to the plurality of fill manifold outlet ports of the second single-use fill manifold.

[0109]

[0121] In some embodiments, the method further includes sequentially delivering an additional supply fluid from each of the other distribution manifold outlets of the single-use distribution manifold to a fill manifold inlet of a corresponding other single-use fill manifold via a respective separate sterile fluid pathway. Portions of the additional supply fluid are delivered from the plurality of fill manifold outlet ports of the corresponding other single-use fill manifold to a corresponding one of the additional set of single-use containers each sterilely fluidly connected to the plurality of fill manifold outlet ports of the corresponding other single-use fill manifold. After delivering each portion of the additional supply fluid, the corresponding other single-use fill manifold is detached from the single-use distribution manifold.

[0110]

[0122] In an embodiment, the method further includes installing the single-use distribution manifold on a loading skid prior to supplying fluid to the distribution manifold inlet of the single-use distribution manifold, and removing the single-use distribution manifold from the loading skid after sequentially delivering additional supply fluid out of each of the other distribution manifold outlets of the single-use distribution manifold.

[0111]

[0123] In an embodiment, the single-use distribution manifold comprises a first single-use distribution manifold. In an embodiment, a first supply fluid is delivered from a first distribution manifold outlet port of the plurality of distribution manifold outlet ports of the single-use distribution manifold by supplying the first supply fluid to a distribution manifold inlet of a second single-use distribution manifold. The second single-use distribution manifold in the first sterile fluid pathway is interposed between a first distribution manifold outlet port of the plurality of distribution manifold outlet ports of the first single-use distribution manifold and a fill manifold inlet of the first single-use fill manifold, and the first supply fluid is delivered from the first distribution manifold outlet port of the plurality of distribution manifold outlet ports of the second single-use distribution manifold via the first sterile fluid pathway to the fill manifold inlet of the first single-use fill manifold.

[0112]

[0124] In another embodiment, a method for aseptically dispensing a fluid includes supplying a first supply fluid to a distribution manifold inlet of a first single-use distribution manifold. The first supply fluid is delivered from a first distribution manifold outlet port of a plurality of distribution manifold outlet ports of the first single-use distribution manifold via a first sterile fluid pathway to a distribution manifold inlet of a second single-use distribution manifold. The first supply fluid is delivered from a first distribution manifold outlet port of the plurality of distribution manifold outlet ports of the second single-use distribution manifold via a second sterile fluid pathway to a fill manifold inlet of a first single-use fill manifold. Multiple portions of the first supply fluid are delivered from the multiple fill manifold outlet ports of the first single-use fill manifold to corresponding ones of a first set of single-use containers each aseptically fluidically connected to the multiple fill manifold outlet ports of the first single-use fill manifold.

[0113]

[0125] After the multiple portions of the first supply fluid have been delivered, the first single-use fill manifold is disconnected from the second single-use distribution manifold, and the second single-use fill manifold is connected to a second outlet port of the multiple distribution manifold outlet ports of the second single-use distribution manifold via a third sterile fluid pathway. A second supply fluid is delivered to a distribution manifold inlet of the first single-use distribution manifold. The second supply fluid is delivered from a first distribution manifold outlet port of the multiple distribution manifold outlet ports of the first single-use distribution manifold via the first sterile fluid pathway to a distribution manifold inlet of the second single-use distribution manifold. The second supply fluid is delivered from a second outlet port of the multiple distribution manifold outlet ports of the second single-use distribution manifold via the third sterile fluid pathway to a fill manifold inlet of the second single-use fill manifold. Each of the multiple portions of the second supply fluid is delivered from the multiple fill manifold outlet ports of the second single-use fill manifold to a corresponding one of a second set of single-use containers that are each aseptically fluidly connected to the multiple fill manifold outlet ports of the second single-use fill manifold.

[0114]

[0126] In an embodiment, the method further includes sequentially delivering the additional supply fluid from each other distribution manifold outlet of the second single-use distribution manifold through a respective separate sterile fluid pathway to a fill manifold inlet of a corresponding other single-use fill manifold, wherein a plurality of portions of the additional supply fluid are delivered from the plurality of fill manifold outlet ports of the corresponding other single-use fill manifold to a corresponding one of the additional set of single-use containers each sterilely fluidly connected to the plurality of fill manifold outlet ports of the corresponding other single-use fill manifold.

[0115]

[0127] In an embodiment, the method further includes, after dispensing each of the multiple portions of the additional supply fluid, removing the corresponding other single-use fill manifold from the second single-use distribution manifold. In an embodiment, the method further includes, after dispensing each of the multiple portions of the additional supply fluid sequentially from each of the other distribution manifold outlets of the second single-use distribution manifold, removing the second single-use distribution manifold and connecting a second outlet port of the multiple distribution manifold outlet ports of the first single-use distribution manifold to a distribution manifold inlet of a third single-use distribution manifold via a fourth sterile fluid pathway.

[0116]

[0128] In an embodiment, the method further includes supplying a third supply fluid to a distribution manifold inlet of the first single-use distribution manifold. The third supply fluid is delivered from a second outlet port of the plurality of distribution manifold outlet ports of the first single-use distribution manifold via a fourth sterile fluid pathway to a distribution manifold inlet of a third single-use distribution manifold. The third supply fluid is delivered from a first outlet port of the plurality of distribution manifold outlet ports of the third single-use distribution manifold via a fifth sterile fluid pathway to a fill manifold inlet of a third single-use fill manifold. Each of the multiple portions of the third supply fluid is delivered from the multiple fill manifold outlet ports of the third single-use fill manifold to a corresponding one of a third set of single-use containers each sterilely fluidly connected to the multiple fill manifold outlet ports of the third single-use fill manifold.

[0117]

[0129] In an embodiment, the method further includes sequentially delivering the additional supply fluid from each other distribution manifold outlet of the third single-use distribution manifold through a respective separate sterile fluid pathway to a fill manifold inlet of a corresponding other single-use fill manifold, wherein a plurality of portions of the additional supply fluid are delivered from the plurality of fill manifold outlet ports of the corresponding other single-use fill manifold to a corresponding one of the additional set of single-use containers each sterilely fluidly connected to the plurality of fill manifold outlet ports of the corresponding other single-use fill manifold.

[0118]

[0130] In an embodiment, the method further includes sequentially delivering a corresponding one of the additional sets of supply fluids from each other distribution manifold outlet of the first single-use distribution manifold to the set of intermediate single-use distribution manifolds.

[0119]

[0131] In another embodiment of a method for aseptically dispensing a fluid according to the principles of the present disclosure, the method includes sequentially delivering a supply fluid from different ones of a plurality of distribution manifold outlet ports of a single-use distribution manifold, each of the distribution manifold outlet ports being in fluid communication with a corresponding one of a corresponding plurality of single-use filling manifolds via a corresponding sterile fluid conduit, wherein the sequential delivery of the supply fluid is accomplished by operating a valve device through a series of different states, for each distribution manifold outlet port, including opening the distribution manifold outlet and closing the other distribution manifold outlet ports.

[0120]

[0132] In embodiments, for each single-use fill manifold, a portion of the supply fluid received from one of the distribution manifold outlet ports in fluid communication therewith is delivered from each of the plurality of fill manifold outlet ports to one of a set of corresponding single-use containers sterilely fluidly connected to the fill manifold outlet ports. In embodiments, the sequential delivery of the supply fluid is performed by operating the valve device to sequentially open each of the sterile fluid conduits and close other sterile fluid conduits.

[0121]

[0133] In another embodiment of a method for aseptically dispensing a fluid according to the principles of the present disclosure, the method includes supplying a supply fluid to a fill manifold inlet of a single-use fill manifold. A fill portion of the supply fluid is dispensed from all but a reserved one of a plurality of fill manifold outlets of a first single-use fill manifold to a single-use container each aseptically fluidically connected to the fill manifold outlet. After dispensing the fill portion, an underfill portion of the supply fluid is dispensed from the reserved one of the fill manifold outlets to a single-use container aseptically fluidically connected to the fill manifold outlet. The underfill portion is less than the fill portion. After dispensing the underfill portion, a fill manifold volume of the supply fluid is drained from a body conduit of the single-use fill manifold out of the reserved one of the fill manifold outlets to a single-use container aseptically fluidically connected to the fill manifold outlet. In some embodiments, the underfill portion and the fill manifold volume combine to be substantially the same as the fill portion.

[0122]

[0134] In embodiments, supplying the supply fluid to the fill manifold inlet includes priming a body conduit of the single-use fill manifold with a fill manifold volume, expelling air in the body conduit through a vent conduit in fluid communication with the body conduit during priming, and closing the vent conduit after priming. In embodiments, delivering the fill portions includes delivering each fill portion sequentially. In embodiments, delivering the fill manifold volume of supply fluid remaining in the body conduit of the single-use fill manifold includes opening a vent conduit in fluid communication with the body conduit and exchanging the fill manifold volume with air in the body conduit during draining.

[0123]

[0135] In an embodiment, the method further includes supplying a supply fluid to a distribution manifold inlet of the single-use distribution manifold. The supply fluid is delivered from a first outlet of a plurality of distribution manifold outlets of the single-use distribution manifold via a first sterile fluid fill pathway to a fill manifold inlet of the single-use fill manifold. After draining the fill manifold volume of supply fluid remaining in the single-use fill manifold, the single-use container is removed from the single-use fill manifold. The distribution manifold volume of supply fluid is drained from the single-use distribution manifold to a sterile fluid reserve pathway to a collection container aseptically fluidly connected to the single-use distribution manifold. The distribution manifold volume includes fluid remaining in a body conduit of the single-use distribution manifold.

[0124]

[0136] In embodiments, supplying a supply fluid to a distribution manifold inlet of the single-use distribution manifold includes introducing recovery fluid from a collection container through a sterile fluid reserve pathway to the distribution manifold inlet such that at least a portion of the supply fluid includes the recovery fluid from the collection container. In embodiments, draining a distribution manifold volume of supply fluid remaining in a body conduit of the single-use distribution manifold includes (i) opening a vent conduit in fluid communication with the body conduit of the single-use distribution manifold, and (ii) opening at least one recovery valve disposed with the first sterile fluid fill pathway to drain the fluid to the collection container.

[0125]

[0137] In embodiments, the single-use distribution manifold comprises an intermediate single-use distribution manifold, and the method further includes supplying a supply fluid to a distribution manifold inlet of the upstream single-use distribution manifold. The supply fluid is delivered from a first distribution manifold outlet of the upstream single-use distribution manifold through a sterile distribution fluid pathway to the distribution manifold inlet of the intermediate single-use distribution manifold. In embodiments, draining the distribution manifold volume of supply fluid includes draining fluid remaining in the single-use distribution manifold and in the upstream single-use distribution manifold. In embodiments, a collection container is positioned below the single-use distribution manifold and the upstream single-use distribution manifold in a direction in which gravity acts on the distribution manifold volume.

[0126]

[0138] In an embodiment, the single-use fill manifold comprises a first single-use fill manifold, the supply fluid comprises a first supply fluid, and the method further includes removing the first single-use fill manifold from the single-use distribution manifold after delivering the fill portion and the underfill portion of the first supply fluid. In an embodiment, the method further includes collecting / draining any fluid remaining in the fill manifold body to a final outlet port and combining the fill manifold with the underfill portion to form a complete delivery portion before removing the fill manifold.

[0127]

[0139] In an embodiment, a fill manifold inlet of the second single-use fill manifold is connected to a second outlet of the plurality of distribution manifold outlets of the single-use distribution manifold via a second sterile fluid fill pathway. A second supply fluid is supplied to the distribution manifold inlet of the single-use distribution manifold. In an embodiment, supplying the second supply fluid includes introducing a recovery fluid from a collection container via a sterile fluid reserve pathway to the distribution manifold inlet such that at least a portion of the second supply fluid includes the recovery fluid from the collection container. The second supply fluid is delivered from a second distribution manifold outlet of the plurality of distribution manifold outlets of the single-use distribution manifold via the second sterile fluid fill pathway to the fill manifold inlet of the second single-use fill manifold. A fill portion of the second supply fluid is delivered from all but a reserved fill manifold outlet of the plurality of fill manifold outlets of the second single-use fill manifold to single-use containers each sterilely fluid-connected to the fill manifold outlet. After the fill portion has been dispensed, an underfill portion of the second supply fluid is dispensed from the reserved one of the fill manifold outlets of the second single-use fill manifold to a single-use container in sterile fluid connection with the fill manifold outlet. After the underfill portion has been dispensed, the fill manifold volume of the second supply fluid remaining in the body conduit of the second single-use fill manifold is drained from the reserved one of the fill manifold outlets of the second single-use fill manifold to a single-use container in sterile fluid connection with the fill manifold outlet.

[0128]

[0140] 13-21, one embodiment of a fluid distribution system 650 constructed in accordance with the principles of the present disclosure and undergoing a fluid recovery sequence is shown. In FIGS. 13-21, dashed line depictions indicate fluid flow paths through the system 650 according to the particular operation being performed.

[0129]

[0141] FIGS. 13-18 illustrate a first fluid recovery sequence in the form of an underfill operation for a single-use container. Referring to FIG. 13, the system 650 can be primed by supplying a supply fluid 651 from a source container(s) to manifolds 653, 654, and 655. A vent conduit 697 above the fill manifold 655 is opened to allow air to be forced out of the series of manifolds 653-655. In FIG. 14, the vent valve 701 is closed in response to liquid reaching a liquid sensor 699 in the vent conduit 697. FIGS. 15 and 16 illustrate sequential fills through the first and second standard fill outlets 681 and 682 of the fill manifold 655, with each container 725 connected to a standard fill outlet being filled to a target volume. Referring to FIG. 16, the remaining standard fill outlets 683-686 can then be filled sequentially. 17, the underfill volume is delivered through underfill outlet 686 of fill manifold 655 to a fluidly connected single-use container 725. Referring to FIG. 18, the fluid in fill manifold 655 is drained from the body of the fill manifold, out underfill outlet 686, and into the bottom container 725 so that each container in rack 700 contains the target volume. Vent conduit 697 is open during the draining operation of fill manifold 655.

[0130]

[0142] 19 and 20 illustrate a second fluid recovery sequence in the form of a distribution manifold draining operation. Referring to FIG. 19, after filling a single-use container stored in workstation 700, the container is removed from fill manifold 655. Vent conduit 697 is opened and fluid in distribution manifolds 653, 654 is allowed to drain (via the influence of gravity) through recovery conduit 106 into recovery container 107. Referring to FIG. 20, once the distribution manifold draining operation is complete, vent conduit 697 can be closed and a new single-use fill manifold 655' can be connected to a different outlet of intermediate distribution manifold 654.

[0131]

[0143] 21 illustrates a third fluid recovery sequence in the form of a manifold priming operation in which fluid from the recovery vessel 107 is used to prime the manifolds 653, 654. Once the fluid in the recovery vessel 107 reaches the low level sensor 118, the system 650 can deliver a new supply of fluid from the original fluid source 651, as shown in FIG.

[0132]

[0144] 13-21 , in embodiments, liquid distribution system 650 may include a suitable integrity test apparatus 735 configured to perform an integrity test on at least one component of system 650. In embodiments, integrity test apparatus 735 is configured to perform an integrity test on at least one of manifolds 653-655. Various integrity test apparatus are suitable for use with embodiments of the present disclosure, such as the PALLTRONIC Flowstar IV Filter Integrity Test Instrument, PALLTRONIC Flowstar IV Filter Integrity Test Instrument MUX Extension, PALLTRONIC Flowstar LGR Test Instrument, or PALLTRONIC AquaWIT IV Filter Integrity Test System, all from Pall Corporation of Port Washington, NY. In embodiments, integrity test apparatus 735 is configured to perform at least one of a leak test and a pressure decay test on at least one of single-use manifolds 653-655.

[0133]

[0145] In an embodiment, the fluid distribution system is configured to be used to provide a closed system that can be used for an "X" set of fill sequences, where the "X" set of fill sequences is equal to the number of outlets in a first distribution manifold. In an embodiment, the fluid distribution system is configured to be used to provide a closed system that can be used for an "X" times "Y" set of fill sequences, where the "X" set of fill sequences is equal to the number of outlets in a first distribution manifold and the "Y" set of fill sequences is equal to the number of outlets in a second distribution manifold connected in series to the first distribution manifold.

[0134]

[0146] All references cited in this specification, including publications, patent applications, and patents, are herein incorporated by reference to the same extent as if each reference was individually and specifically indicated to be incorporated by reference and was set forth in its entirety herein.

[0135]

[0147] Use of the terms "a," "an," and "the" and similar referents in the context of describing the present invention (particularly in the context of the claims below) should be construed to encompass both the singular and the plural unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "containing" should be construed as open-ended terms (i.e., meaning "including, but not limited to") unless otherwise indicated. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of individually referring to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated herein as if it were individually listed herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context. Any and all examples provided herein, or the use of exemplary language (e.g., "such as"), are intended merely to better clarify the invention and do not limit the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0136]

[0148] Preferred embodiments of the present invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of these preferred embodiments will become apparent to those skilled in the art upon reading the foregoing description. The inventors expect those skilled in the art to employ such variations as they see fit, and the inventors intend the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, this invention includes any combination of the above-described elements in all possible variations thereof unless otherwise indicated herein or clearly contradicted by context.

Claims

1. 1. A fluid distribution system comprising a pump, a single-use fill manifold, a fill valve apparatus, and a control unit, the pump is configured to selectively generate a flow of fluid; the single-use fill manifold includes a fill manifold inlet, a plurality of fill manifold outlets, and a fill manifold body conduit, the fill manifold inlet being in fluid communication with each of the plurality of fill manifold outlets via the fill manifold body conduit, the fill manifold inlet being disposed with the pump to deliver a supply fluid to the single-use fill manifold, the fill manifold outlets including at least one standard fill outlet and an underfill outlet; the filling valve arrangement includes a plurality of valves disposed with the single-use filling manifold such that each of the filling manifold outlets is independently closeable via a corresponding one of the valves of the filling valve arrangement; 11. The fluid distribution system of claim 10, wherein the control unit includes a processor and a non-transitory computer readable medium having a fluid distribution program, the processor being configured with the computer readable medium to execute the fluid distribution program, the processor being in electrical communication with the pump and the fill valve apparatus to selectively operate the pump and the valve of the fill valve apparatus based on instructions from the fluid distribution program, the fluid distribution program comprising a container filling module configured to deliver a target fill volume of the supply fluid from each standard fill outlet of the fill manifold outlets, deliver an underfill volume of the supply fluid from the underfill outlet of the fill manifold outlet, and drain a fill manifold volume of the supply fluid from the fill manifold body conduit out of the underfill outlet of the fill manifold outlet, the underfill volume being less than the target fill volume.

2. Further comprising a plurality of single-use containers; each of the single-use containers having an access port fluidly connected to a corresponding one of the fill manifold outlets via a sterile fluid connector; The container fill module of the fluid dispensing program, when executed by the processor, supplying the supply fluid to the fill manifold inlet of the single-use fill manifold; sequentially delivering the target fill volume of fluid from each of the standard fill outlets of the single-use fill manifold to the single-use containers in aseptic fluid connection therewith; after the target fill volume has been sequentially delivered, delivering the underfill volume of fluid from the underfill outlet of the single-use fill manifold to the single-use container in sterile fluid connection with the underfill outlet; after dispensing the underfill volume, draining the fill manifold volume of fluid from the fill manifold body conduit out of the underfill outlet and into the single-use container in sterile fluid connection to the underfill outlet; The fluid distribution system of claim 1 configured to implement:

3. a vent conduit in fluid communication with the fill manifold body conduit; a vent valve disposed with the vent conduit to selectively close the vent conduit and operatively disposed with the control unit; The fluid distribution system of claim 1 or 2, further comprising:

4. a vent liquid sensor disposed within the vent conduit and configured to generate a liquid detection signal in response to detecting liquid in the vent conduit, the control unit being in electrical communication with the vent liquid sensor to receive the liquid detection signal from the vent liquid sensor; an air filter, the air filter being disposed with the vent conduit, the vent valve being interposed between the vent liquid sensor and the air filter; Further equipped with The fluid distribution system of claim 3 , wherein the control unit is configured to stop operation of the pump and / or close the vent valve in response to receiving the liquid detection signal.

5. When executed by the processor, priming the fill manifold body conduit of the single-use fill manifold with the fill manifold volume of the supply fluid; expelling air within the fill manifold body conduit through the vent conduit while the vent valve is in an open position during priming of the fill manifold body conduit; placing the vent valve in a closed position to close off the vent conduit after the fill manifold body has been primed; 5. The fluid distribution system of claim 3 or 4, comprising a fill manifold priming module configured to perform:

6. a single-use distribution manifold including a distribution manifold inlet, a plurality of distribution manifold outlets, and a distribution manifold body conduit, the distribution manifold inlet in fluid communication with each of the plurality of distribution manifold outlets via the distribution manifold body conduit, one of the plurality of distribution manifold outlets in aseptic fluid connection with the fill manifold inlet, the distribution manifold inlet disposed with the pump to deliver the supply fluid to the single-use fill manifold via one of the distribution manifold outlets; a distributor valve arrangement including a plurality of valves disposed with the single-use distributor manifold, such that each of the distributor manifold outlets is independently closeable via a corresponding one of the valves of the distributor valve arrangement; The fluid distribution system of any one of claims 1 to 5, further comprising:

7. a collection container and a sterile fluid pre-path, said collection container in fluid communication with said distribution manifold body conduit via said sterile fluid pre-path; 7. The fluid distribution system of claim 6, further comprising a distribution manifold drain module configured to drain a distribution manifold volume of the supply fluid in the distribution manifold body conduit to the sterile fluid reserve path to the collection container when the fluid distribution program is executed by the processor.

8. a vent conduit in fluid communication with the fill manifold body conduit; a vent valve disposed with the vent conduit to selectively close the vent conduit and operatively disposed with the control unit; a recovery valve, the recovery valve being disposed with the sterile fluid reserve path such that the sterile fluid reserve path is closable via the recovery valve, the recovery valve being operably disposed with the control unit; Further equipped with the collection vessel is disposed downward in a direction in which gravity acts on the distribution manifold volume, the vent valve, and the single-use distribution manifold; 8. The fluid distribution system of claim 7, wherein the distribution manifold drain module, when executed by the processor, is configured to open the vent valve to allow air to flow from outside the vent conduit into the distribution manifold body conduit and open the recovery valve disposed with a first sterile fluid fill path.

9. a recovered liquid upper limit sensor disposed with the collection container and configured to generate a recovered liquid upper limit signal in response to detecting a predetermined high level of liquid in the collection container, the control unit being in electrical communication with the recovered liquid upper limit sensor to receive the recovered liquid upper limit signal from the recovered liquid upper limit sensor; 9. The fluid distribution system of claim 8, wherein the distribution manifold drain module, when executed by the processor, is configured to close the vent valve and close the recovery valve disposed with the first sterile fluid fill path in response to receiving the recovered liquid high limit signal.

10. the single-use distribution manifold comprises an intermediate single-use distribution manifold; The fluid distribution system comprises: an upstream single-use distribution manifold including an upstream distribution manifold inlet, a plurality of upstream distribution manifold outlets, and an upstream distribution manifold body conduit, wherein the upstream distribution manifold inlet is in fluid communication with each of the plurality of upstream distribution manifold outlets via the upstream distribution manifold body conduit, one of the plurality of upstream distribution manifold outlets is in aseptic fluid connection with the distribution manifold inlet of the intermediate single-use distribution manifold, and the upstream distribution manifold inlet is disposed with the pump to deliver the supply fluid to the single-use filling manifold; an upstream distribution valve arrangement including a plurality of valves disposed with the upstream single-use distribution manifold, such that each of the upstream distribution manifold outlets is independently closeable via a corresponding one of the valves of the upstream distribution valve arrangement; The fluid distribution system of any one of claims 6 to 9, further comprising:

11. 1. A method of aseptically dispensing a fluid, comprising: providing a supply fluid to a fill manifold inlet of a single-use fill manifold; delivering fill portions of the supply fluid from all but a reserved fill manifold outlet of a plurality of fill manifold outlets of the single-use fill manifold to single-use containers in sterile fluid connection to the fill manifold outlets; after delivering the fill portion, delivering an underfill portion of the supply fluid from the reserved one of the fill manifold outlets to a single-use container in sterile fluid connection with the fill manifold outlet, the underfill portion being smaller than the fill portion; draining a fill manifold volume of the supply fluid from a body conduit of the single-use fill manifold through the reserved one of the fill manifold outlets into the single-use container in sterile fluid connection thereto after delivering the underfill portion; A method comprising:

12. 12. The method of claim 11, wherein the step of draining the fill manifold volume of the supply fluid remaining in the body conduit of the single-use fill manifold includes opening a manifold vent in fluid communication with the body conduit and exchanging the fill manifold volume with air in the body conduit during draining.

13. 13. The method of claim 12, wherein the step of supplying the supply fluid to the fill manifold inlet includes priming the body conduit of the single-use fill manifold with the fill manifold volume, expelling air within the body conduit through the manifold vent in fluid communication with the body conduit during priming, and closing the manifold vent after priming.

14. The method of any one of claims 11 to 13, wherein the step of delivering the fill portions comprises delivering each fill portion in sequence.

15. The method of any one of claims 11 to 14, wherein the underfill portion and the fill manifold volume combined are substantially the same as the fill portion.

16. supplying the supply fluid to a distribution manifold inlet of a single-use distribution manifold; delivering the supply fluid from a first distribution manifold outlet of a plurality of distribution manifold outlets of the single-use distribution manifold through a first sterile fluid fill path to the fill manifold inlet of the single-use fill manifold; removing the single-use container from the single-use fill manifold after draining the fill manifold volume of the supply fluid remaining in the single-use fill manifold; draining a distribution manifold volume of the supply fluid from the single-use distribution manifold into a sterile fluid reserve path to a collection container in sterile fluid connection to the single-use distribution manifold; The method of any one of claims 11 to 15, further comprising:

17. 17. The method of claim 16, wherein the step of supplying the supply fluid to the distribution manifold inlet of the single-use distribution manifold comprises introducing recovery fluid from the collection container through the sterile fluid reserve path to the distribution manifold inlet such that at least a portion of the supply fluid comprises recovery fluid from the collection container.

18. 18. The method of claim 16 or 17, wherein the step of draining the distribution manifold volume of the supply fluid remaining in the body conduit of the single-use distribution manifold comprises opening a manifold vent in fluid communication with the body conduit of the single-use distribution manifold and opening at least one recovery valve disposed with the first sterile fluid fill path.

19. the single-use distribution manifold comprises an intermediate single-use distribution manifold; The method comprises: supplying the supply fluid to a distribution manifold inlet of an upstream single-use distribution manifold; delivering the supply fluid from a first distribution manifold outlet of a plurality of distribution manifold outlets of the upstream single-use distribution manifold through a sterile distribution fluid pathway to the distribution manifold inlet of the intermediate single-use distribution manifold; Further equipped with 19. The method of claim 16, wherein the step of draining the distribution manifold volume of the supply fluid comprises draining fluid remaining in the single-use distribution manifold and the upstream single-use distribution manifold, and the collection vessel is positioned below the single-use distribution manifold and the upstream single-use distribution manifold in a direction in which gravity acts on the distribution manifold volume.

20. the single-use fill manifold comprises a first single-use fill manifold and the supply fluid comprises a first supply fluid; The method comprises: removing the first single-use fill manifold from the single-use distribution manifold after delivering the fill and underfill portions of the first supply fluid; connecting a fill manifold inlet of a second single-use fill manifold to a second distribution manifold outlet of the plurality of distribution manifold outlets of the single-use distribution manifold via a second sterile fluid fill path; supplying a second supply fluid to the distribution manifold inlet of the single-use distribution manifold, the supplying of the second supply fluid comprising introducing a recovery fluid from the collection container through the sterile fluid prep path to the distribution manifold inlet such that at least a portion of the second supply fluid comprises recovery fluid from the collection container; delivering the second supply fluid from the second distribution manifold outlet of the plurality of distribution manifold outlets of the single-use distribution manifold through the second sterile fluid fill path to the fill manifold inlet of the second single-use fill manifold; delivering fill portions of the second supply fluid from all but a reserved fill manifold outlet of the second single-use fill manifold to single-use containers in sterile fluid connection thereto; after delivering the fill portion, delivering an underfill portion of the second supply fluid from the reserved one of the fill manifold outlets of the second single-use fill manifold to a single-use container in sterile fluid connection with the fill manifold outlet; draining a fill manifold volume of the second supply fluid remaining in a body conduit of the second single-use fill manifold after delivering the underfill portion from the reserved one of the fill manifold outlets of the second single-use fill manifold to the single-use container in sterile fluid connection to the reserved one; The method of any one of claims 16 to 19, further comprising:

Images