Patent Publication Number: US-2022211579-A1

Title: Dual Container System for Product Reconstitution

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This is a divisional of U.S. patent application Ser. No. 16/630,994, filed Jan. 14, 2020, which is the U.S. national phase of International Patent Application No. PCT/US18/41801, filed Jul. 12, 2018, which claims priority U.S. Provisional Patent Application No. 62/533,380, filed Jul. 17, 2017, the entire contents of each of which are incorporated by reference herein. 
     Additionally, the following related and co-owned applications are hereby expressly incorporated by reference herein in their entirety: U.S. Provisional Application Ser. No. 62/533,362, having Attorney Docket No.: 31203/52018P (entitled STERILE PRODUCT BAG WITH FILTERED PORT); U.S. Provisional Application Ser. No. 62/533,408, having Attorney Docket No.: 31203/52032P (entitled MEDICAL PRODUCT INCLUDING PRE-FILLED PRODUCT BAG WITH FILTERED FLUID PORT); U.S. Provisional Application Ser. No. 62/533,427, having Attorney Docket No.: 31203/52050P (entitled FILTERED PRODUCT BAG WITH COMPACT FORM FACTOR); and U.S. Provisional Application Ser. No. 62/533,440, having Attorney Docket No.: 31203/52062P (entitled MEDICAL SYRINGE SYSTEM WITH FILTERED FILLING PORT), each filed on Jul. 17, 2017. 
    
    
     FIELD OF THE DISCLOSURE 
     This disclosure relates to a system for reconstituting a concentrate and, more particularly, a dual container system for reconstituting and sterilizing a non-sterile concentrate. 
     BACKGROUND 
     Often, drugs and nutrients are mixed with a pharmaceutical fluid such as a diluent before being delivered to a patient. The diluent may be, for example, a dextrose solution, a saline solution or even water. Many such drugs or nutrients are supplied in a concentrated form such as powder, liquid, gel, foam, etc., and packaged in glass or plastic vials. 
     In order for the concentrate to be administered to a patient, it must first undergo reconstitution. As used herein, the term reconstitution includes not only liquidization of non-liquid concentrates but also dilution of liquid concentrates. 
     One way of reconstituting a concentrate is first to inject a diluent into the vial holding the concentrate. This may typically be performed by a syringe having a liquid diluent contained in the syringe barrel. After the rubber stopper of the vial is pierced by the syringe needle, the liquid is injected into the vial. The vial is shaken to reconstitute and dilute the concentrate with the liquid. The liquid is then withdrawn back into the syringe. These steps may be repeated several times to ensure complete reconstitution of the concentrate. After the final mixing, the syringe is withdrawn and the reconstituted product may then be injected into a medication port of a parenteral solution container (e.g., an IV bag) containing a medical solution or diluent such as dextrose or saline solution. The drug, now diluted with the medical solution in the parenteral solution container, is delivered through an administration set for intravenous administration to the patient. 
     Some known parenteral solution containers have even been developed to include a device for connecting directly to the vial, thereby bypassing the need for the syringe. Such devices utilize a cannula extending from the parenteral container and with a sharp exterior end sealed inside of a sheath with a removable closure. When reconstitution is required, the removable closure can be removed and a vial containing concentrate is pierced with the sharp end of the cannula to provide for fluid communication back and forth between the vial and the interior chamber of the parenteral container. This allows the user to mix the component and ultimately store them in the parenteral container for administration to the patient. 
     Due to the necessity for only sterile solutions being delivered to patients, the drug or nutrient concentrate and even the pharmaceutical fluid used for reconstitution must be sterile prior to, during, and after reconstitution is performed. Thus whether the drug or nutrient is reconstituted and added to an IV bag using a syringe or vial attachment prior to administration, the steps to reconstitute and add should be undertaken in a manner and in an environment to reduce the potential of contamination. For example, frequently these steps are undertaken within a laminar flow fume hood found in the pharmacy. Although these hoods may offer an effective amount of space, there is still a general hindrance in undertaking the reconstitution and addition and also the risk of contamination cannot be completely removed. If the steps are undertaken in other areas of the health care setting, the risk of contamination may be even greater. 
     Moreover, the drug or nutrient and the containers in which they reside are typically provided to hospitals or pharmacists, for example, pre-filled and pre-sterilized. For concentrates, these must be either filled into their containers in an aseptic environment and/or filled and subsequently sterilized. Aseptic filling can be tedious, costly, and time consuming. While sterilizing filled containers can be cost effective, certain drugs can be sensitive to heat and therefore steam sterilization is not an option. Other forms of sterilization can be much more costly and time consuming. Aseptic filling can also pose a risk that the concentrate is not at desired level of sterility prior to reconstitution and addition to the IV bag. 
     SUMMARY 
     One aspect of the present disclosure provides a system for reconstituting and sterilizing a concentrate includes a mixing container, a filtration device, and a product bag. The a mixing container has an inlet port and outlet port in fluid communication with a mixing chamber disposed between the inlet port and the outlet port. The mixing chamber is adapted to contain a product concentrate. The filtration device has an inlet and an outlet, the inlet of the filtration device coupled to the outlet port of the mixing container. The filtration device includes a filter membrane with a nominal pore size in a range of approximately 0.1 μm to approximately 0.5 μm. The product bag has an inlet port coupled to the outlet of the filtration device, and has a bladder defining an empty sterile chamber for receiving sterilized and reconstituted product resulting from mixing a pharmaceutical fluid with a product concentrate in the mixing chamber to obtain a mixture then introduced through the filtration device to obtain the reconstituted and sterilized product. 
     In some aspects, the system also includes a product concentrate disposed in the mixing chamber. 
     In some aspects, the product concentrate in the mixing chamber is a non-sterile product concentrate. 
     In some aspects, the filter membrane is shaped as (a) a hollow fiber with a wall and pores residing in the wall of the fiber, or (b) a flat filter disposed within a rectangular, square or box-like filter housing, the flat filter having a wall and pores residing in the wall. 
     In some aspects, the filtration device comprises a stem and the filter membrane is disposed in line with the stem between the inlet and outlet of the filtration device. 
     In some aspects, the stem defines a seal-and-cut area between the filter membrane and the inlet port of the product bag, the seal-and-cut area adapted to allow the stem to be sealed and cut to close the inlet port of the product bag. 
     In some aspects, the filter membrane comprises a plurality of filter membranes. 
     In some aspects, the filter membrane includes an inlet end and an outlet end, wherein the outlet end is sealed and the inlet end is an open inlet. 
     In some aspects, the filter membrane has a wall thickness in the range of approximately 150 μm to approximately 500 μm. 
     In some aspects, the filter membrane has a longitudinal dimension in the range of approximately 3 cm to approximately 420 cm, an inner diameter in the range of approximately 2 mm to approximately 4 mm, and an outer diameter in the range of approximately 2.3 mm to approximately 5 mm. 
     In some aspects, the filter membrane is made of at least one of the following materials: a polyolefin, polyvinylidene fluoride, polymethylmethacrylate, polyacrylonitrile, polysulfone, polyethersulfone, and a polymer containing cationic charges. 
     In some aspects, the stem is one of a flexible stem or a rigid stem. 
     In some aspects, the stem is made of at least one of the following materials: PVC, PET, a poly(meth)acrylate, a polycarbonate, a polyolefin, a cycloolefin copolymer, polystyrene, or a silicone polymer. 
     In some aspects, the filter membrane includes at least one U-shaped hollow fiber filter membrane secured in a U-shaped configuration by a filter membrane housing contained within a filter body. 
     In some aspects, the filter membrane includes a plurality of U-shaped hollow fiber filter membranes. 
     In some aspects, the filter membrane comprises a plurality of parallel hollow fiber membrane filters secured in a side-by-side configuration. 
     In some aspects, the filter membrane comprises a plurality of parallel hollow fiber membrane filters arranged in a circular pattern. 
     In some aspects, the filter membrane has a nominal pore size in a range of approximately 0.1 μm to approximately 0.22 μm. 
     In some aspects, the non-sterile product concentrate comprises a medicinal or nutritional concentrate disposed. 
     In some aspects, the mixing container comprises a drip chamber with two open ends, one of the open ends being the inlet port for receiving a diluent. 
     In some aspects, the mixing container comprises a vial with two open ends, one of the open ends being the inlet port for receiving a diluent. 
     In some aspects, wherein the mixing container comprises a bag defining the inlet port adapted to receive a diluent. 
     In some aspects, the mixing container comprises a vial with a single open end, and the system further comprises a vial adaptor defining the inlet port and outlet port, the vial adaptor further defining a mixing port coupled to the single open end of the vial. 
     In some aspects, the vial adaptor further comprises a first conduit establishing fluid communication between the inlet port and the mixing port, and a second conduit establishing fluid communication between the mixing port and the outlet port. 
     In some aspects, each of the first and second conduits includes a terminal end that is disposed within the vial, the terminal end of the first conduit extending further into the vial than the second terminal end. 
     In some aspects, the product bag further comprises an administration port separate from the inlet port of the product bag for facilitating administration of the reconstituted and sterilized product to a patient. 
     Another aspect of the present disclosure provides a system for reconstituting a non-sterile concentrate, wherein the system includes a mixing container, a non-sterile concentrate, and a filtration device. The mixing container has an inlet port and outlet port in fluid communication with a non-sterile mixing chamber disposed between the inlet port and the outlet port. The non-sterile product concentrate is disposed in the mixing chamber. The filtration device has an inlet and an outlet, the inlet of the filtration device coupled to the outlet port of the mixing container. The filtration device also having a filter membrane disposed between the inlet and outlet of the filtration device and having a nominal pore size in a range of approximately 0.1 μm to approximately 0.5 μm, for producing sterilized and reconstituted product resulting from mixing a pharmaceutical fluid with the non-sterile product concentrate in the mixing chamber to obtain a non-sterile mixture then introduced through the filtration device to obtain the reconstituted and sterilized product. 
     In some aspects, the system also includes a product bag having an inlet port adapted to be coupled to the outlet of the filtration device, the product bag having a bladder defining an empty sterile chamber for receiving the reconstituted and sterilized product from the outlet of the filtration device. 
     In some aspect, the system further includes a syringe with a delivery end adapted to be coupled to the outlet of the filtration device, the syringe having a syringe barrel defining a reservoir, a plunger, and a stopper slidably disposed in the reservoir, the reservoir defining an empty sterile chamber for receiving the reconstituted and sterilized product from the outlet of the filtration device. 
     In some aspects, the filter membrane is shaped as (a) a hollow fiber with a wall and pores residing in the wall of the fiber, or (b) a flat filter disposed within a rectangular, square or box-like filter housing, the flat filter having a wall and pores residing in the wall 
     In some aspects, the filtration device comprises a stem and the filter membrane is disposed in line with the stem. 
     In some aspects, the stem defines a seal-and-cut area between the filter membrane and the inlet port of the product bag, the seal-and-cut area adapted to allow the stem to be sealed and cut to close the inlet port of the product bag. 
     In some aspects, the filter membrane comprises a plurality of filter membranes. 
     In some aspects, the filter membrane includes an inlet end and an outlet end, wherein the outlet end is sealed and the inlet end is an open inlet. 
     In some aspects, the filter membrane has a wall thickness in the range of approximately 150 μm to approximately 500 μm. 
     In some aspects, the filter membrane has a longitudinal dimension in the range of approximately 3 cm to approximately 420 cm, an inner diameter in the range of approximately 2 mm to approximately 4 mm, and an outer diameter in the range of approximately 2.3 mm to approximately 5 mm. 
     In some aspects, the filter membrane is made of at least one of the following materials: a polyolefin, polyvinylidene fluoride, polymethylmethacrylate, polyacrylonitrile, polysulfone, polyethersulfone, and a polymer containing cationic charges. 
     In some aspects, the stem is one of a flexible stem or a rigid stem. 
     In some aspects, the stem is made of at least one of the following materials: PVC, PET, a poly(meth)acrylate, a polycarbonate, a polyolefin, a cycloolefin copolymer, polystyrene, or a silicone polymer. 
     In some aspects, the filter membrane includes at least one U-shaped hollow fiber filter membrane secured in a U-shaped configuration by a filter membrane housing contained within a filter body. 
     In some aspects, the filter membrane includes a plurality of U-shaped hollow fiber filter membranes. 
     In some aspects, the filter membrane comprises a plurality of parallel hollow fiber membrane filters secured in a side-by-side configuration. 
     In some aspects, the filter membrane comprises a plurality of parallel hollow fiber membrane filters arranged in a circular pattern. 
     In some aspects, the filter membrane has a nominal pore size in a range of approximately 0.1 μm to approximately 0.22 μm. 
     In some aspects, the non-sterile product concentrate comprises a medicinal or nutritional concentrate disposed. 
     In some aspects, the mixing container comprises a drip chamber with two open ends, one of the open ends being the inlet port for receiving a diluent. 
     In some aspects, the mixing container comprises a vial with two open ends, one of the open ends being the inlet port for receiving a diluent. 
     In some aspects, the mixing container comprises a bag defining the inlet port adapted to receive a diluent. 
     In some aspects, the mixing container comprises a vial with a single open end, and the system further comprises a vial adaptor defining the inlet port and outlet port, the vial adaptor further defining a mixing port coupled to the single open end of the vial. 
     In some aspects, the vial adaptor further comprises a first conduit establishing fluid communication between the inlet port and the mixing port, and a second conduit establishing fluid communication between the mixing port and the outlet port. 
     In some aspects, each of the first and second conduits includes a terminal end that is disposed within the vial, the terminal end of the first conduit extending further into the vial than the second terminal end. 
     In some aspects, the product bag further comprises an administration port separate from the inlet port of the product bag for facilitating administration of the reconstituted and sterilized product to a patient. 
     Yet another aspect of the present disclosure provides a method of reconstituting and sterilizing a concentrate. The method includes providing a mixing container having an inlet port and outlet port in fluid communication with a non-sterile mixing chamber disposed between the inlet port and the outlet port, a non-sterile product concentrate disposed in the mixing chamber, and a filtration device having an inlet and an outlet, the inlet of the filtration device coupled to the outlet port of the mixing container, the filtration device comprising a filter membrane disposed between the inlet and outlet of the filtration device and having a nominal pore size in a range of approximately 0.1 μm to approximately 0.5 μm. The method also includes introducing a pharmaceutical fluid into the mixing chamber through the inlet port of the mixing container. The method also includes mixing the pharmaceutical fluid and concentrate to obtain non-sterile reconstituted product. The method also includes passing the reconstituted product through the outlet port of the mixing chamber and through the filtration device to obtain sterilized and reconstituted product. 
     In some aspects, the method also includes providing a product bag having an inlet port coupled to the outlet of the filtration device, the product bag having a bladder defining an empty sterile chamber, and introducing the sterilized and reconstituted product into the sterile chamber of the product bag from the outlet of the filtration device. 
     In some aspects, the method further includes providing a syringe with a delivery end adapted to be coupled to the outlet of the filtration device, the syringe having a syringe barrel defining a reservoir, a plunger, and a stopper slidably disposed in the reservoir, the reservoir defining an empty sterile chamber; and introducing the sterilized and reconstituted product into the sterile chamber of the syringe from the outlet of the filtration device. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a plurality of filter membranes. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through an open outlet end and a sealed outlet end of the hollow fiber of the filter membrane. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a filter membrane having a wall thickness in the range of approximately 150 μm to approximately 500 μm. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a filter membrane having a longitudinal dimension in the range of approximately 3 cm to approximately 420 cm, an inner diameter in the range of approximately 2 mm to approximately 4 mm, and an outer diameter in the range of approximately 2.3 mm to approximately 5 mm. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a filter membrane made of at least one of the following materials: a polyolefin, polyvinylidene fluoride, polymethylmethacrylate, polyacrylonitrile, polysulfone, polyethersulfone, and a polymer containing cationic charges. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a filter having at least one U-shaped hollow fiber filter membrane secured in a U-shaped configuration by a filter membrane housing contained within a filter body. 
     In some aspects, passing non-sterile reconstituted product through a filter having at least one U-shaped hollow fiber filter membrane comprises passing the non-sterile reconstituted product through a plurality of U-shaped hollow fiber filter membranes. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a plurality of parallel hollow fiber membrane filters secured in a side-by-side configuration. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a plurality of parallel hollow fiber membrane filters arranged in a circular pattern. 
     In some aspects, passing the non-sterile reconstituted product through the filtration device comprises passing the non-sterile reconstituted product through a filter membrane having a nominal pore size in a range of approximately 0.1 μm to approximately 0.22 μm. 
     In some aspects, the method further includes sealing and cutting the filtration device at a location between the filter membrane and the inlet port of the product bag to close the inlet port of the product bag. 
     In some aspects, the method further includes performing a filter integrity test on the filter. 
     In some aspects, the method further includes removing the filtration device from the mixing container prior to performing the filter integrity test. 
     In some aspects, performing the filter integrity test comprises one of a pressure degradation test, a bubble point test, a water intrusion test, or a water flow test. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       While the specification concludes with claims particularly pointing out and distinctly claiming the subject matter that is regarded as the present disclosure, it is believed that the disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the figures may have been simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omissions of elements in some figures are not necessarily indicative of the presence or absence of particular elements in any of the exemplary embodiments, except as may be explicitly delineated in the corresponding written description. None of the drawings are necessarily to scale. 
         FIG. 1  is a front view of a first embodiment of a dual container system for reconstituting and sterilizing a concentrate in accordance with the present disclosure; 
         FIG. 1A  is an exploded cross-sectional side view of one version of a removable attachment between a mixing container and a filtration device of the system of  FIG. 1 ; 
         FIG. 1B  is an assembled cross-sectional side view of the removable attachment of  FIG. 1A ; 
         FIG. 1C  is an exploded cross-sectional side view of an alternative version of a removable attachment between a mixing container and a filtration device of the system of  FIG. 1 ; 
         FIG. 1D  is an assembled cross-sectional side view of the removable attachment of  FIG. 1C ; 
         FIG. 2  is a front view of a second embodiment of a dual container system for reconstituting and sterilizing a concentrate in accordance with the present disclosure; 
         FIG. 3  is a front view, partially in cross-section, of a third embodiment of a dual container system for reconstituting and sterilizing a concentrate in accordance with the present disclosure; 
         FIG. 3A  is a schematic cross-sectional detail of a vial adaptor of  FIG. 3 ; 
         FIG. 4  is a cross-sectional detail view of the vial adaptor of  FIG. 3  connected to an associated vial; 
         FIG. 5  is an expanded isometric view of one embodiment of a filtration device for use with the system of any one of  FIGS. 1-3 ; 
         FIG. 6  is a perspective view of an alternative connector for use with the filtration device of  FIG. 5 ; 
         FIG. 7  is a side cross-sectional view of the connector of  FIG. 6 ; 
         FIG. 8  is a side view of the connector of  FIG. 6 ; 
         FIG. 9  is a bottom view of the connector of  FIG. 8 ; 
         FIG. 10  is a top view of the connector of  FIG. 8 ; 
         FIG. 11  is a front view of an alternative filtration device for use with any of the systems of  FIGS. 1-3 ; 
         FIG. 12  is a front view of another alternative filtration device for use with any of the systems of  FIGS. 1-3 ; 
         FIG. 13  is a front view of yet another filtration device for use with any of the systems of  FIGS. 1-3  having a plurality of hollow fiber membranes secured side by side; 
         FIG. 14  is an isometric view of the securement device used for the plurality of hollow fiber membranes depicted in  FIG. 13 ; 
         FIG. 15  is an isometric view of a fiber bundle for a product bag having a plurality of hollow fiber membranes secured in a circular holder; 
         FIG. 16  is an exploded perspective view of an alternative connector for use with a three-filter filter bundle; 
         FIG. 17  is a side exploded view of the connector of  FIG. 16 ; 
         FIG. 18  is a exploded perspective view of another alternative connector for use with a seven-filter filter bundle; 
         FIG. 19  is a side exploded view of the connector of  FIG. 18 ; 
         FIG. 20  is a bottom view of the connector of  FIG. 19 ; and 
         FIG. 21  is a front view, partially in cross-section, of an alternative version of the dual container system of  FIG. 3 . 
     
    
    
     DETAILED DESCRIPTION 
     The present disclosure is directed to a novel system and method for reconstituting a product concentrate, which can be sterile or non-sterile, and subsequently passing the resultant product through a sterilizing filter. Generally, the system includes a mixing container that stores the optionally non-sterile product concentrate such as a drug or nutrient in the form of a powder, a gel, a foam, a liquid, etc. The mixing container includes an inlet port adapted to receive a diluent, and an outlet port coupled to an inlet of a sterilization filtration device. In one embodiment, the outlet of the filtration device is coupled to a product bag with a pre-sterilized inner chamber such that sterilized product departing the filtration device flows into the product bag for subsequent storage and administration. One benefit of this arrangement is that the product concentrate need not be stored in the mixing container in a sterile condition, or while the concentrate can be introduced into the mixing container in a sterile condition, there is less importance on the need to maintain and/or monitor that sterility throughout shipping and storage. Another advantage is that this arrangement allows for reconstitution to be performed on-demand at a hospital or pharmacy, for example. That is, the system can be provided containing only the product concentrate. A pharmacist can introduce a diluent to reconstitute the product in the mixing container, which is then pushed through the sterilization filter to result in a sterile product ready for patient administration. This on-demand process greatly reduces the risk of pre-sterilized products becoming contaminated, and also reduces the cost of managing and verifying sterile materials, as well as shipping heavy prefilled bags of pre-sterilized pharmaceutical fluid. 
     To meet the foregoing, the present disclosure provides multiple embodiments of reconstitution and sterilization systems. A first embodiment described primarily with reference to  FIG. 1  includes a mixing container in the form of a simple drip chamber or two open ended vial.  FIG. 2  includes a mixing container in the form of a medical bag.  FIGS. 3 and 21  each includes a mixing chamber that embodies a conventional drug vial. While the mixing containers can vary, each embodiment shares a common and unique technical features and principle of operation. 
       FIG. 1  illustrates a first embodiment of a system  200  for reconstituting and sterilizing a product concentrate in accordance with the present disclosure. The system  200  includes a mixing container  202 , a product bag  206 , and a filtration device  204  coupled between the mixing container  202  and product bag  204 . As shown in  FIG. 1 , in some versions the mixing container  202  is a separate container adapted to be connected to and also removable from the filtration device  204 , as will be discussed below. In other versions, the mixing container  202  can be provided pre-attached to the filtration device  204 . 
     The mixing container  202 , as shown, contains a volume of a product concentrate  208 . The product concentrate  208  can include a drug concentrate or a nutrient concentrate, for example, and may be in the form of a powder, a liquid, a gel, a foam, or any other concentrated form requiring reconstitution prior to patient administration. As mentioned, in some embodiments, the concentrate  208  can be sterile or non-sterile. The filtration device  204  includes an inlet  218 , an outlet  220 , and a filter membrane  222  disposed between the inlet and outlet  218 ,  220 . The product bag  206  includes a generally conventional medical bag constructed of medical grade films to define a bladder  224  that is a fillable pouch having a sterile interior chamber  226  with a standard volume capacity. The chamber  226  can be sterilized through any known means such as steam sterilization, Gamma irradiation, etc. At least partially surrounding a perimeter of the bladder  224  is a sealed perimeter  228  having a plurality of apertures  230  configured to receive mounting hang pins during filling, administration, and/or storage. The chamber  226  of the bladder  224  is fluidly connected to an inlet port  232  of the bladder  206 . An administration port  234  is disposed on the bladder  206  for being coupled to an administration set to facilitate patient administration. Other ports can be included as desired. 
     Still referring to  FIG. 1 , the mixing container  202  of the present embodiment can include a drip chamber or a glass vial  216  having an inlet port  212 , an outlet port  214 , and a mixing chamber  216  between the inlet and outlet ports  212 ,  214 . In some versions, the inlet port  212  can include a septum or other piercable membrane. The mixing chamber  216  as well as the product concentrate  208  stored in the mixing chamber  216  can be non-sterile or sterile. The outlet port  214  of the mixing container  202  is coupled, preferably directly, to the inlet  218  of the filtration device  204 . The outlet  220  of the filtration device  220  is coupled, preferably directly, to the inlet port  232  of the product bag  206 . 
     As mentioned briefly above, in some embodiments, the outlet port  214  of the mixing container  202  can be permanently attached to the inlet  218  of the filtration device  204 . In other embodiments, the outlet port  214  of the mixing container  202  can be removably attached to the inlet  218  of the filtration device  204  in order to facilitate a filter integrity test, as will be described below. For example,  FIGS. 1A-1D  depict two different possible coupling mechanisms for removably attaching and detaching the mixing container  202  to the filtration device  204 . In  FIGS. 1A and 1B , the outlet port  214  of the mixing container  202  can include a piercable diaphragm or septum  215  and the inlet  218  of the filtration device can include a shroud  217  and piercing member  219 . So configured, the outlet port  214  can be brought into contact with the inlet  218  of the filtration device  204  such that the piercing member  219  pierces the diaphragm or septum  215  to establish a fluid pathway between the mixing container  202  and the filtration device  204 , as shown in  FIG. 1B . In some versions, the connection between mixing container  202  and the filtration device  204  shown in  FIG. 1B  can be maintained with friction present between the outlet port  214  and the shroud  217 , between the outlet port  214  and the piercing member  219 , between the outlet port  214  and the diaphragm or septum  215 , or some other means. Thus, to detach the mixing container  202  from the filtration device  204 , a simple axial force may be applied to overcome the friction fit. For example,  FIGS. 1C and 1D  illustrate an alternative, similar to  FIGS. 1A and 1B , but where the mixing container  202  and filtration device  204  are attached and detached through a threaded connection. Specifically, as shown, the outlet port  214  of the mixing container  202  can have external threads  221  and the shroud  217  of the filtration device  204  can have internal threads  223  that threadably engage the external threads  221 . So configured, when attaching the mixing container  202  to the filtration device  204 , the piercing member  219  penetrates the diaphragm or septum  215  and relative rotation of the mixing container  202  and filtration device  204  cause the internal and external threads  221 ,  223  to engage, thereby attaching the components together. Thus, to detach the mixing container  202  from the filtration device  204 , opposite relative rotation can unthread the outlet port  214  from the inlet  218 . 
     Referring back to  FIG. 1 , when the system  200  is fully assembled, a pharmaceutical fluid such as a water, saline, a solution, a diluent, etc. used for reconstituting concentrates can be introduced into the inlet port  212  of the mixing chamber  202  to mix with the product concentrate  208 . Because the mixture will subsequently be passed through a sterilizing filter, the pharmaceutical fluid can be sterile or non-sterile. The user may take certain actions (e.g., shaking, swirling, rocking, etc.) to facilitate mixing the fluid and the concentrate in the mixing chamber  216  while additional fluid is introduced into the mixing chamber  216  to begin forcing the mixture out of the mixing container  202  and through the filtration device  204 . As the mixture flows into the filtration device  204 , the mixture filters through the filter membrane  222 , resulting in a sterilized and reconstituted product flowing out of the outlet  220  of the filtration device  204  and into the product bag  206 . 
     In some embodiments, the filtration device  204 , as shown in  FIG. 1 , includes a stem  236 , in line with which the filter membrane  222  is mounted. In the version of  FIG. 1 , the stem  236  is shown as only extending below the filter membrane  222 , but in other versions, the stem  236  may also extend above the filter membrane  222  and/or the filter membrane  222  may be physically disposed inside of the stem  236 . Regardless, the stem  236  in  FIG. 1  is located between the filter membrane  222  and the inlet port  232  of the product bag  206  and constitutes an essentially hollow conduit region defining a “seal and cut area”. The phrase “seal and cut area” pertains to the manner in which the product bags are sealed and cut after introducing fluid to the chamber  226  through the filtration device  204 . That is, the disclosed arrangement is designed such that after the product bag  206  receives the reconstituted and sterilized product from the filtration device  222 , a sealing mechanism can be employed to seal the stem  236  closed in the “seal and cut area,” which is below the filter membrane  222  but above the inlet port  232  of the product bag  206 . Thus, the “seal and cut area”  238  in this version is a portion of the stem  236  above the product bag  206  where the filter membrane  222  does not reside. Sealing of the “seal and cut area”  238  can be achieved with a heat sealer or any other device, including for example clamping a clamp onto the “seal and cut area”  238 . Once the stem  236  is sealed, the stem  236  is cut at a location above the seal but below the filter membrane  222 . Cutting may be achieved with a knife or any other device. The stem  236  provides an isolated fluid connection between the inlet  232  and the chamber  226  of the bladder  224  of the product bag  206 , such that once the product is filtered through the filter membrane  222 , the reconstituted and sterilized product passes directly into the sterilized environment of the empty chamber  226  of the bag  206 . Hence, after the bag  206  receives the reconstituted and sterilized product and the stem  236  is sealed and cut, the reconstituted and sterilized product in the bladder  226  remains sterile until the bladder  224  is punctured or compromised. This, of course, assumes that the filtration device  204  was uncompromised prior to filling and performed as desired. 
     To ensure that the filter membrane  222  performed properly, a filter integrity test can be performed. A filter integrity test is facilitated by the arrangement of the “seal and cut area”  238  of the stem  236 , which allows for the filter membrane  222  to be separated intact from the remainder of the now-sealed product bag  206 . For example, after the stem  236  and filter membrane  222  are separated from the product bag  206 , a filter testing device (not shown) may be pre-programmed or controlled to perform a filter integrity test on the filter membrane  222 . Examples of filter integrity tests might include a bubble point test, a pressure degradation test, a water intrusion test, a water flow test, or any suitable test known in the art. A pressure degradation test is a method for testing the quality of a filter either before or after the filter has been used. In the preferred embodiment, the filter membrane  222  is tested after the mixture passes through the filter membrane  222  and into the product bag  206 . To perform the filter integrity test using a pressure degradation test procedure, the filtration device  204  not only removed from the product bag  206 , but also preferably removed from the mixing container  202 . For example, the outlet port  214  of the mixing container  202  can be removably attached to the inlet  218  of the filtration device in the manners described above with respect to  FIGS. 1A-1D  and, as such, the mixing container  202  can easily be removed from the filtration device  204  prior to performing the filter integrity test. Thus, with the mixing container  202  detached, a test head (not shown) applies an air pressure of a predetermined value to the inlet  218  and filtration device  204 . In one embodiment, the pre-determined value is the pressure where gas cannot permeate the filter membrane  222  of an acceptable filtration device  204 . A pressure sensor, or other method of measuring the integrity of the filter, is located within the test head and measures the pressure decay or diffusion rate through the filter membrane  222 . The results from the integrity test are assessed to determine the quality of the filter membrane  222 , and therefore the quality of the solution that previously passed through the filter membrane  222  and into the product bag  206 . If the pressure sensor measures a decay or a unexpected rate of decay, then the filtration device  204  fails the test and it can be determined that the solution in the product bag is unsatisfactory. Alternatively in a bubble point test, the test head gradually increases the pressure applied to the filter membrane  222 , and the increase in pressure is measured in parallel with the diffusion rate of the gas through the filter membrane  222 . Any disproportionate increase in diffusion rate in relation to the applied pressure may indicate a hole or other structural flaw in the filter membrane  222 , and the filter would fail the integrity test. 
     Thus, it can be appreciated that the disclosed arrangement of the “seal and cut area”  238  disclosed herein advantageously facilitates the filter integrity test, and a determination that the fluid in the product bag is either sterile or has the potential of being compromised may be made with a high degree of certainty. 
       FIG. 2  depicts a second embodiment of a system  200  for reconstituting and sterilizing concentrate in accordance with the teachings of the present disclosure. Like the system of  FIG. 1 , the system of  FIG. 2  includes a mixing container  202 , a product bag  206 , and a filtration device coupled between the mixing container  202  and product bag  206 . Same as that described above, the mixing container  202  includes an outlet port  214  that can be either permanently attached or removably attached to the inlet  218  of the filtration device  204  using one of the connections described in  FIGS. 1A-1D  or any other suitable connection. The filtration device  204  and product bag  206  in  FIG. 2  are identical to the same components in  FIG. 1 , so the details will not be repeated. The mixing container  202 , however, is distinct from that described with reference to  FIG. 1 . 
     In  FIG. 2 , the mixing container  202  includes a construct similar to the product bag  206  in that it is constructed of medical grade films to define a bladder  240  that is a fillable pouch having an interior chamber  242  with a standard volume capacity. And, in the interior chamber  242 , resides a volume of a product concentrate  250 . In contrast to the product bag  206 , the chamber  242  of the mixing container  202  need not be sterile. In fact, both the chamber  242  and the concentrate  250  disposed in the chamber  242  can be non-sterile or sterile in accordance with the teachings and benefits of the present disclosure. At least partially surrounding a perimeter of the bladder  240  is a sealed perimeter  244  having a plurality of apertures  246  configured to receive mounting hang pins during filling, administration, and/or storage. The chamber  242  of the bladder  240  is fluidly connected to an inlet port  248  of the bladder  240 . The inlet port  248  may be an open port or may include a septum or membrane that is adapted to be pierced by a filling nozzle during a filling operation, for example. Additional ports or openings may also be provided, as depicted, such as a pair of medicine ports for introducing additional fluids as may be desired. 
     From the foregoing, it should be appreciate that the process for reconstituting and sterilizing the non-sterile product concentrate  250  in the system  200  of  FIG. 2  is substantially identical to the process described above with respect to  FIG. 1 . As such, the details will not be repeated. One difference in the process may include the fact that the mixing container  202  in  FIG. 2  is a flexible bag, which lends itself to manual manipulation. As such, as a pharmaceutical fluid is introduced into the chamber  242  through the inlet port  248 , the user may manually manipulate and/or massage the bladder  240  to facilitate mixing of the pharmaceutical fluid and concentrate  250  prior to passing the mixture through the filtration device  204 . 
       FIG. 3  depicts a third embodiment of a system  200  for reconstituting and sterilizing concentrate in accordance with the teachings of the present disclosure. Like the system of  FIGS. 1 and 2 , the system of  FIG. 3  includes a mixing container  202 , a product bag  206 , and a filtration device  204  coupled between the mixing container  202  and product bag  206 . Same as that described above with respect to  FIGS. 1 and 2 , the mixing container  202  includes an outlet port  214  that can be either permanently attached or removably attached to the inlet  218  of the filtration device  204  using one of the connections described in  FIGS. 1A-1D  or any other suitable connection. The filtration device  204  and product bag  206  in  FIG. 3  are identical to the same components in  FIGS. 1 and 2 , so the details will not be repeated. The details of the mixing container  202 , however, are distinct from that described with reference to  FIGS. 1 and 2 . 
     In  FIG. 3 , the mixing container  202  includes a traditional vial  252  in combination with a vial adaptor  254 . The vial  252  defines an interior chamber  256  containing a volume of a product concentrate  258 , and an opening  260 , which can include a rubber stopper  262  or other fitment for attaching to the vial adaptor  254 , as will be described. As with prior embodiments, the chamber  256  of the mixing container  202  of  FIG. 3  need not be sterile. In fact, both the chamber  256  and the concentrate  258  disposed in the chamber  256  can be non-sterile or sterile in accordance with the teachings and benefits of the present disclosure. 
     As seen in  FIGS. 3 and 3A , the vial adaptor  254  includes a T-shaped connector including an inlet port  264 , an outlet port  266 , and a mixing port  268 . The mixing port  268  is connected to the vial  252  and, more particularly, the opening  260  of the vial  252 . In the version of  FIG. 3 , the inlet port  264  of the vial adaptor  254  is connected to a first fill tube  270  and the outlet port  266  is connected to a second fill tube  272 . The first and second fill tubes  270 ,  272  can be threadably or otherwise connected to the inlet and outlet ports  264 ,  266 , respectively. An opposite end of the second fill tube  272  is also connected to the inlet  218  of the filtration device  204 . In some embodiments, the second fill tube  272  can be removably attached to the inlet  218  of the filtration device  204  such as to facilitate removal of the mixing container for performing a filter integrity test. In some embodiments, the second fill tube  272  can be removably attached to the filtration device  204  using one of the connections described in  FIGS. 1A-1D  or any other suitable connection. In other embodiments, the vial adaptor  254  could be provided without either or both of the fill tubes  270 ,  272  such that, in some versions, the outlet port  266  is connected directly to the inlet  218  of the filtration device  204 . In that case, the outlet port  266  can be removably attached to the filtration device  204  using one of the connections described in  FIGS. 1A-1D  or any other suitable connection. 
     As shown in more detail in  FIG. 3A , the mixing port  268  of the vial adaptor  254  further includes a first conduit  272  and a second conduit  274 , which as depicted in  FIG. 4 , assist with flowing fluid through the mixing container  202  during use. Specifically, as depicted in  FIG. 4 , the first conduit  272  includes a terminal end  276  and the second conduit  274  includes a terminal end  278 , each terminal end  276 ,  278  disposed inside of the chamber  256  of the vial  252 . In this version, the terminal end  276  of the first conduit  272  extends further into the chamber  256  than the terminal end  278  of the second conduit  274  for facilitating mixing and reducing the potential for backflow during use because as oriented during use, the first conduit  272  is positioned above the second conduit  274  in the direction of gravity. That is, during use, the vial  252  would most likely be oriented “upside down” such that the rubber stopper of the vial  252  would be at the bottom, so the conduits  272 ,  274  extend generally upward. In this configuration, the terminal end  276  of the first conduit  272  is located above the terminal end  278  of the second conduct  274  such that the terminal end  278  of the second conduit  274  is located at the bottom of the vial  252  to facilitate the drainage of the drug solution into the final product bag  206 . With the vial adaptor  254  configured as described, it can be seen in  FIG. 3A , that the adaptor  254  defines in inlet flow path  280  and an outlet flow path  282 . The inlet flow path  280  begins at the inlet port  265  and flows to the terminal end  276  of the first conduit  272 . The outlet flow path  282  begins at the terminal end  278  of the second conduit  274  and flows to the outlet port  266 . 
     From the foregoing, it should be appreciate that the process for reconstituting and sterilizing the product concentrate  258  in the system  200  of  FIG. 3  is substantially identical to the process described above with respect to  FIGS. 1 and 2 . As such, the details will not be repeated. The primary distinction would be that the pharmaceutical fluid passing through the inlet port  264  of the vial adaptor  254  and into the vial  252  must flow through the first flow path  280 , which includes in the depicted version one ninety-degree turn. Similarly, the mixture leaving the vial  252  through the mixing port  268  of the vial adaptor  254  must flow through the second flow path  282 , which also includes in the depicted version one ninety-degree turn. The structure of these flow paths and rigidity of the vial  252  may benefit from the user manually manipulating the vial  252  to facilitate mixing of the pharmaceutical fluid and concentrate  258  in a manner similar to that described with reference to the mixing container  202  of  FIG. 1 . While the adaptor  254  of the disclosed version is T-shaped and includes conduits  280 ,  282  with ninety-degree turns, other versions of the adaptor  254  are contemplated. 
     As mentioned, during use of the foregoing systems  200 , a pharmacist or other technician must introduce a pharmaceutical fluid such as a diluent into the mixing container  202  to begin reconstituting the product concentrate. This can be accomplished manually, automatically, or semi-automatically. 
     As mentioned, each of the foregoing embodiments includes a filtration device  204  for sterilizing the mixture of concentrate and pharmaceutical fluid before the mixture reaches the product bag  206 . While each of the foregoing embodiments includes a product bag  206  coupled to the outlet  220  of the filtration device  204 , in other versions of the present disclosure, the system  200  does not require the product bag  206 . In such versions, the outlet  220  of the filtration device  204  can be adapted to be connected to a different storage facility, an administration set for direct patient administration, or otherwise. As such, it should be understood that in the present disclosure of the system  200 , the product bag  206  is an optional aspect. 
     For example,  FIG. 21  depicts one alternative version of the system  200  described above with reference to  FIG. 3  for reconstituting and sterilizing concentrate in accordance with the teachings of the present disclosure. Like the system of  FIG. 3 , the system in  FIG. 21  includes a mixing container  202  and a filtration device  204 . Distinct, however, is that the system  200  in  FIG. 21  does not include a product bag  206 . Instead, it includes a syringe  500  on the receiving end of the filtration device  204 . The syringe  500  can be generally conventional and include a syringe barrel  502  defining a cavity or reservoir, a plunger  504  connected to a stopper  506  disposed in the cavity or reservoir, and a delivery end  508 . As shown, the delivery end  508  of the syringe  500  is connected to the filtration device  204 . All other aspects, structural and functional, of the mixing container  202  and filtration device  204  in  FIG. 21  can be identical to those described in reference to  FIGS. 3-4  and, as such, the details will not be repeated. So configured, one the reconstituted product has been sufficiently delivered into the syringe  500 , the mixing container  202  can be removed from the filtration device  204 , and the filtration device can be removed from the delivery end  508  of the syringe  500  for integrity testing. Then, the product in the syringe  500  can be delivered to a patient with a needle through an administration set or other means as is generally known. 
     As described, the filtration device  204  of the systems  200  include a filter membrane  222 . The filter membrane  222  can take various forms to achieve the intended sterilization. For example, as shown in  FIG. 5 , one embodiment of a filtration device  204 . While all of the reference numerals used in  FIG. 5  do not directly correlate to those used in  FIGS. 1-3 and 21 , it should be appreciated that the filtration device  204  in  FIGS. 1-3 and 21  can be embodied by the filtration device  204  of  FIG. 5 . In  FIG. 5 , the filtration device  204  has a filter  155  that can be a hollow fiber membrane with one sealed end  158  and one open inlet end  160 . The sealed end  158  can be capped or it may be sealed with a heat seal, an adhesive, or some other means. A plurality of pores  162  along the surface  164  of the filter  155  allow a pharmaceutical fluid that entered the filter  155  at the open inlet end  160  to exit the filter  155 . In one version, the stem  156  surrounds the filter membrane  170  in a generally concentric configuration so filtered pharmaceutical fluid exiting the filter membrane  170  is contained within the stem  156  and ultimately passed, in some embodiments, to the product bag  206 . 
     As depicted in  FIG. 5 , a hollow connector  166  can be used to secure the stem  156  and the filter  155  together. The open inlet end  160  of the filter  155  is sealingly connected to an open outlet end  168  of the hollow connector  166 . The connection may be achieved by gluing the open inlet end  160  of the filter  155  to the open outlet end  168  of the connector  166  with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector  166  such as cyclohexanone. In the version depicted, the open outlet end  168  of the connector  166  comprises a hollow cylindrical member that fits inside of and is fixed to the open inlet end  160  of the filter  155 . As such, an outer diameter of the open outlet end  168  of the connector  166  is substantially similar to or slightly smaller than an inner diameter of the open inlet end  160  of the filter  155 . In some versions, the open inlet end  160  of the filter  155  may be welded to the open outlet end  168  of the connector  166  by, for example, heat welding (e.g., introducing a hot conical metal tip into the open inlet end  150  of the filter  155  to partially melt it), laser welding if the hollow connector  166  is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filter  155  may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector  166 . Other designs and configurations for connecting the filter  155  to the connector  166  are intended to be within the scope of the present disclosure. 
     The hollow connector  166  further includes a fluid inlet  169  for connecting to the outlet port  214  of the mixing container  202  of any of  FIGS. 1-3 and 21 , for example. In some versions, the fluid inlet  169  can include a Luer type fitting or other standard medical fitting. The mixture from the mixing container  202  can then travel through the hollow connector  166  and exit into the filter  155  through the open outlet end  168  of the hollow connector  166 . The hollow connector  166  also includes a sealing surface  172  to which the stem  156  is attached. The sealing surface  172  in this version is cylindrical and has a diameter larger than a diameter of the open outlet end  168 , and is disposed generally concentric with the open outlet end  168 . In fact, in this version, the outer diameter of the sealing surface  172  is generally identical to or slightly smaller than an inner diameter of the stem  156 . So configured, the stem  156  receives the sealing surface  172  and extends therefrom to surround and protect the filter  155  without contacting the surface  164  of the filter  155 . The stem  156  can be fixed to the sealing surface  172  with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem  156  receives the pharmaceutical solution after it passes through the pores  162  in the filter  155 . From there, the now filtered solution passes into the bladder  152 . 
       FIGS. 6-10  illustrate an alternative hollow connector  766 , similar to connector  166 , for securing the stem  156  and the hollow fiber filter  155  of  FIG. 5  together. The connector  766  includes an open outlet end  768  carried by a stem structure that extends in a first direction from a bearing plate  777  and is adapted to be sealingly connected to the open inlet end  160  of the filter  155 . The connection may be achieved by gluing the open inlet end  160  of the filter  155  to the open outlet end  768  of the connector  766  with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector  766  such as cyclohexanone. In the version depicted, the stem structure of the open outlet end  768  of the connector  766  comprises a hollow cylindrical member that fits inside of and is fixed to the open inlet end  160  of the filter  155 . As such, an outer diameter of the open outlet end  768  of the connector  766  is substantially similar to or slightly smaller than an inner diameter of the open inlet end  160  of the filter  155 . In some versions, the open inlet end  160  of the filter  155  may be welded to the open outlet end  768  of the connector  766  by, for example, heat welding (e.g., introducing a hot conical metal tip into the open inlet end  150  of the filter  155  to partially melt it), laser welding if the hollow connector  766  is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filter  155  may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector  766 . Other designs and configurations for connecting the filter  155  to the connector  766  are intended to be within the scope of the present disclosure. 
     The hollow connector  766  further includes a fluid inlet  769 , which is also a stem structure, extending in a second direction (opposite the first direction) from the bearing plate  777 . The fluid inlet  769  of the hollow connector  766  is adapted to connect to the outlet port  214  of the mixing container  202  of  FIGS. 1-3 and 21 , for example. In some versions, the fluid inlet  769  can include a Luer type fitting or other standard medical fitting. The mixture from the mixing container  202  can then travel through the hollow connector  766  and exit into the filter  155  through the open outlet end  768  of the hollow connector  766 . 
     The hollow connector  766  also includes a sealing surface  772  to which the stem  156  is attached. The sealing surface  772  in this version is a cylindrical shroud extending from the bearing plate  777  in the first direction and has a diameter larger than a diameter of the open outlet end  768 . The sealing surface  772  is disposed generally concentric with the open outlet end  768 . As such, in this embodiment, the shroud of the sealing surface  772  surrounds the stem structure of the open outlet end  768  such that an annular gap  779  resides between the two. In fact, in this version, the outer diameter of the sealing surface  772  is generally identical to or slightly smaller than an inner diameter of the stem  156 . So configured, the sealing surface  772  of the connector  766  can be received by the stem  156  such that the stem  156  extends therefrom to surround and protect the filter  155  without contacting the surface  164  of the filter  155 . The stem  156  can be fixed to the sealing surface  772  with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem  156  receives the mixture after it passes through the pores  162  in the filter  155 . From there, the now filtered product passes, in come embodiments, to the product bag  206 . 
     While the foregoing version of the filtration device  204  has been described as including a single filter membrane  170 , in other embodiments within the scope of the present disclosure, the filtration device  204  may include multiple filter membranes  170 . A few non-limiting examples of multiple membrane filters will be discussed below. 
     In one version of the foregoing assembly of  FIG. 5 , and as mentioned, the stem  156  includes an inner diameter that is larger than an outer diameter of the filter membrane  170 , and the stem  156  includes a longitudinal dimension that is larger than a longitudinal dimension of the filter membrane  170 . As such, when the stem  156  and filter membrane  170  are assembled onto the connector  166 , the filter membrane  170  resides entirely within (i.e., entirely inside of) the stem  156  and a gap exists between the inner sidewall of the stem  156  and the outer sidewall of the filter membrane  170 . As such, fluid passing into the filter membrane  170  passes out of the plurality of pores  162  and flows without obstruction through the gap and along the inside of the stem  156  to the bladder. In some versions, the stem  156  can be a flexible tube, a rigid tube, or can include a tube with portions that are flexible and other portions that are rigid. Specifically, in some versions, a stem  156  with at least a rigid portion adjacent to the filter membrane  170  can serve to further protect the filter membrane  170  and/or prevent the filter membrane  170  from becoming pinched or kinked in a flexible tube. In other versions, such protection may not be needed or desirable. In one embodiment, the stem  156  has an internal diameter in the range of approximately 2.5 mm to approximately 8 mm, and a longitudinal dimension in the range of approximately 5 cm to approximately 30 cm. In one embodiment, the internal diameter of the stem  156  is about 0.2 to about 3 mm larger than the outer diameter of the filter membrane  170 . And, the filter membrane  170  has an outer diameter in the range of approximately 2.3 mm to approximately 5 mm, a longitudinal dimension in the range of approximately 3 cm to approximately 420 cm, and a wall thickness in the range of approximately 150 μm to approximately 500 μm. Furthermore, in one version each of the plurality of pores  162  in the filter membrane  170  have a diameter less than or equal to approximately 0.2 microns. In some versions, each pore has a diameter less than or equal to a value in a range of approximately 0.1 microns to approximately 0.5 microns, for instance, approximately 0.2 to approximately 0.4 microns. In some versions, each pore has a diameter that is less than or equal to approximately 0.22 microns. In some versions, each pore has a diameter that is less than or equal to a value in a range of approximately 0.1 microns to approximately 0.2 microns. In some versions, each pore has a diameter that is less than or equal to a value in a range of approximately 0.1 microns to approximately 0.22 microns. These pore sizes coupled with the disclosed geometrical dimension of the stem  156  and filter membrane  170  ensure acceptable flow rates through the filter membrane  170  for filling the product bags with patient injectable solutions such as sterile water, sterile saline, etc. In other versions, any or all of the dimensions could vary depending on the specific application. 
     Suitable materials for the filter membrane  170  can include polyolefins (e.g., PE, PP), polyvinylidene fluoride, polymethylmethacrylate, polyacrylonitrile, polysulfone, and polyethersulfone. In some embodiments within the scope of the present disclosure, the filter  155  may be comprised of a blend of polysulfone or polyethersulfone and polyvinylpyrrolidone. In other embodiments within the scope of the present disclosure, the filter membrane  170  can include a polymer containing cationic charges, e.g. polymers bearing functional groups like quaternary ammonium groups. A suitable example for such polymers is polyethyleneimine. The filter membrane  170  may be manufactured by known techniques including, e.g., extrusion, phase inversion, spinning, chemical vapor deposition, 3D printing, etc. Suitable materials for the stem  156  include PVC, polyesters like PET, poly(meth)acrylates like PMMA, polycarbonates (PC), polyolefins like PE, PP, or cycloolefin copolymers (COC), polystyrene (PS), silicone polymers, etc. 
     Additional details regarding some possible versions of the filter and the specific construction of the membrane, for example, can be described in European Patent Application No. EP16152332.9, entitled FILTER MEMBRANE AND DEVICE, filed Jan. 22, 2016, and additionally in PCT/EP2017/051044, entitled FILTER MEMBRANE AND DEVICE, filed Jan. 19, 2017, the entire contents of each of which are expressly incorporated herein by reference. 
     Thus far, the hollow fiber membrane  170  in  FIG. 5 , for example, has been described as being located within the stem  156 . In other embodiments, the filter  155  may include its own housing or other support structure, which is coupled to the stem  156  either in place of the connector  166  in  FIG. 5  or connector  766  in  FIGS. 6-10 , or at a location between two portions of the stem  156 . 
     For example,  FIG. 11  is a front view of a filter assembly  1000  for a product bag (not pictured) having a single U-shaped hollow fiber filter membrane  1002  contained within a filter body  1004 . The filter membrane  1002  is secured to a filter membrane housing  1006  in the U-shaped configuration with an adhesive (i.e., a UV curing acrylic adhesive), an epoxy, welding, bonding, or other means. The filter membrane housing  1006  is connected to the filter body  1004  at an outlet portion  1008  of the filter body  1004 . An inlet portion  1010  is sealably connected to the outlet portion  1008  of the filter body  1004  at a joint or other seam. The inlet portion  1010  of the filter body  1004  has an inlet  1012  by which a pharmaceutical fluid may enter the filter assembly  1000 . The mixture from the mixing container  202  then enters the filter membrane  1002  through a plurality of pores  1014 , travels through the filter membrane  1002 , exits the filter membrane  1002  at filter membrane outlets  1016 , and exits the filter body  1004  at filter outlet  1018 . The filter outlet  418  may then be connected to the product bag  206 , as shown in  FIGS. 1-3 and 21 . In  FIG. 11 , the flow of fluid through the assembly  1000  has been described as moving from the inlet  1012  of the inlet portion  1010  to the outlet  1018  of the outlet portion  1008 . However, the same assembly  400  could be used in the opposite direction such that fluid enters the outlet  1018  of the outlet portion  1008  and exits the inlet  1012  of the inlet portion  1010 . In this alternative configuration, fluid would first enter the inlet  1018 , pass into the filter membrane  1002  at the filter membrane outlets  1016 , and exit through the pores  1014  and finally the inlet  1012 . 
       FIG. 12  is an alternate embodiment of the filter assembly  1000  depicted in  FIG. 11 . In  FIG. 12 , the filter  1020  includes two U-shaped hollow fiber filter membranes  1022  are secured to a filter membrane housing  1024  in the U-shaped configuration with an adhesive (i.e., a UV curing acrylic adhesive), an epoxy, welding, bonding, or some other means. The filter membranes  1022  and filter membrane housing  1024  are contained within a filter body  1026  having an inlet portion  1028  with inlet  1030  sealably connected to an outlet portion  1032  having filter outlet  1034 . In other embodiments, a filter may include more than two U-shaped hollow fiber filter membranes arranged as depicted in  FIGS. 11 and 12 . In  FIG. 12 , like in  FIG. 11 , the flow of fluid through the assembly  1000  has been described as moving from the inlet portion  1028  to the outlet portion  1032 . However, the same assembly  1000  could be used in the opposite direction such that fluid enters the outlet portion  1032  and exits the inlet portion  1028  as described above relative to  FIG. 11 . 
       FIG. 13  is a further alternative filter assembly. Specifically, in  FIG. 13 , a plurality of linear membrane filters  502  are secured directly together in a parallel side-by-side configuration for what can be referred to as a fiber bundle. The filters  502  in  FIG. 13  can be secured together with adhesive (i.e., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. In other versions, the plurality of filters  502  can be manufactured together as one piece by way of any of the manufacturing techniques described above. 
       FIG. 14  provides another alternative in which a securement device  504  includes a number of blocks defining a plurality of grooves  506  identical to the number of hollow fiber membrane filters  502 . The blocks of the securement device  504  may be sandwiched together and used to hold the plurality of hollow fiber membrane filters  502  in the side-by-side configuration. The securement device  504  depicted in  FIG. 14  allows for two sets of the hollow fiber membrane filters  502  of  FIG. 13  to be stacked relative to each other. The fiber bundle including the membrane filters  502  and the securement device  504  may be placed in a filter body, such as that discussed with respect to  FIGS. 11 and 12 . 
       FIG. 15  is an isometric view of another version of a fiber bundle  600  for a filtration device  204  having a plurality of parallel hollow fiber membrane filters  502  similar to  FIGS. 13 and 14 , but wherein the parallel filters  502  are arranged in a circular pattern by a circular holder  504 . The fiber bundle  600  may be placed in a filter body, such as that discussed with respect to  FIGS. 11 and 12 . 
       FIGS. 16-17  and  FIGS. 18-20  illustrate two additional devices for coupling fiber bundles to a stem in accordance with the present disclosure.  FIGS. 16-17  discloses a connector  866  for connecting a three-fiber bundle to a stem. Specifically, the connector  866  includes a first hollow body  866   a  and a second hollow body  866   b.  The first body  866   a  includes a solution inlet  869 , which is a stem structure, extending from a bearing plate  877 . A mixture from the mixing container  202  can be fed into the fluid inlet  869  of the first hollow body  866   a  of the connector  866 . In some versions, the fluid inlet  869  can include a Luer type fitting or other standard medical fitting. 
     The hollow connector  866  also includes a sealing surface  872  to which the stem  156  is attached. The sealing surface  872  in this version is a cylindrical shroud extending from the bearing plate  877  in a direction opposite to a direction of extension of the fluid inlet  869 . The sealing surface  872  is disposed generally concentric with the fluid inlet  869 . As such, in this embodiment, the shroud of the sealing surface  872  defines a cylindrical cavity (not shown in the drawings) for receiving a portion of the second hollow body  866   b  of the connector  866 . 
     The second hollow body  866   b,  as depicted, includes a support plate  880  and three open outlet ends  868  extending from the support plate  880 . Additionally, the support plate  880  includes an outer diameter that is essentially the same as or slightly smaller than an inner diameter of the cavity of the shroud of the sealing surface  872  such that when assembled, the support plate  880  is positioned into the cavity. In one version, the support plate  880  includes a seal member  882  around its periphery to form a fluid tight seal with the inner surface of the shroud of the sealing surface  872  when inserted into the cavity. Friction, adhesive, or some other means may retain the support plate  880  in connection with the shroud of the sealing surface  872 . 
     As mentioned, the second body  866   b  includes three open outlet ends  868  extending from the support plate  880 . Each open outlet end  868  is adapted to be sealingly connected to an open inlet end  160  of one of three filters  155 . The connection may be achieved by gluing open inlet ends  160  of the filters  155  to the open outlet ends  868  with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector  766  such as cyclohexanone. In the version depicted, the stem structure of the open outlet ends  868  of the connector  866  comprises a hollow cylindrical member that fits inside of and is fixed to the open inlet ends  160  of the filters  155 . As such, an outer diameter of the open outlet ends  868  is substantially similar to or slightly smaller than an inner diameter of the open inlet ends  160  of the filters  155 . In some versions, the filters  155  may be welded to the open outlet ends  868  of the connector  866  by, for example, heat welding (e.g., introducing a hot conical metal tip into the open inlet ends  150  of the filters  155  to partially melt it), laser welding if the hollow connector  866  is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filters  155  may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector  866 . Other designs and configurations for connecting the filters  155  to the open outlet ends  868  are intended to be within the scope of the present disclosure. 
     Finally, as with previously described embodiments, the sealing surface  872  of the connector  866  can be received by the stem  156  such that the stem  156  extends therefrom to surround and protect the filters  155  without contacting the surfaces  164  of the filters  155 . The stem  156  can be fixed to the sealing surface  872  with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem  156  receives the pharmaceutical solution after it passes through the pores  162  in the filter  155 . From there, the now filtered solution passes into the bladder  152  in the same manner described above with respect to  FIGS. 3-5 . 
       FIGS. 18-20  discloses a connector  966  for connecting a seven-fiber bundle to a stem. Specifically, the connector  966  includes a first hollow body  966   a  and a second hollow body  966   b  that can be connected to the first hollow body  966   a  with an adhesive or via other means. The first body  966   a  includes a solution inlet  969 , which is a stem structure, extending from a bearing plate  977 . A mixture from the mixing container  202  can be fed into the fluid inlet  969  of the first hollow body  966   a  of the connector  966 . In some versions, the fluid inlet  969  can include a Luer type fitting or other standard medical fitting. 
     The second hollow body  966   b,  as depicted, includes a hollow cylindrical support collar  980  in which seven hollow fiber membrane filters  955  can be disposed parallel to each other, as shown in  FIGS. 18 and 20 . In one version, the support collar  980  can include a support plate  982  carrying seven open outlet ends  968  extending into the collar  980  for connecting to the filters  955  in a manner similar to that described above regarding  FIGS. 16-17 . The connection may be achieved by gluing the filters  955  to the open outlet ends  968  with, for example, an epoxy resin, a polyurethane resin, a cyanoacrylate resin, a UV curing acrylic adhesive, or a solvent for the material of the hollow connector  966  such as cyclohexanone. In the version depicted, the stem structure of the open outlet ends  868  of the connector  866  comprises a hollow cylindrical member that fits inside of and is fixed to the filters  955 . As such, a diameter of the open outlet ends  968  is substantially similar to or slightly smaller than an inner diameter of the filters  955 . In some versions, the filters  955  may be welded to the open outlet ends  968  of the connector  966  by, for example, heat welding (e.g., introducing a hot conical metal tip into the filters  955  to partially melt it), laser welding if the hollow connector  966  is made from a material that absorbs laser radiation, mirror welding, ultrasound welding, and friction welding. Alternately, the filters  955  may be inserted into a mold, and a thermoplastic polymer may be injection-molded around it to form the hollow connector  966 . Other designs and configurations for connecting the filters  955  to the open outlet ends  968  are intended to be within the scope of the present disclosure. 
     Finally, the collar  980  of this embodiment includes a sealing surface  972  that can be received by the stem  156  such that the stem  156  extends therefrom. The stem  156  can be fixed to the sealing surface  972  with adhesive (e.g., a UV curing acrylic adhesive), epoxy, welding, bonding, etc. The stem  156  receives the mixture after it passes through the pores  162  in the filters  955 . From there, the now sterilized passes into the product bag  206  in the same manner described above with respect to any of  FIGS. 1-5 . 
     From the foregoing, it can be seen that various filtering arrangements can serve the principles of the present disclosure including introducing a reconstituted to the product bag in a sterilized manner. And while the filtration device  204  throughout the disclosure has been described as including a hollow fiber filter or a plurality of hollow fiber filters, in other versions of the disclosure the filtration device  204  can include other forms of filter assemblies including, for example, a flat filter disposed within a rectangular, square or box-like filter housing. The flat filter could have any of the same characteristics as the hollow fiber filter described herein, only its geometrical shape and configuration would be different. 
     While certain representative versions of the claimed subject matter have been described herein for purposes of illustrating the invention, it will be apparent to those skilled in the art that various changes in the devices and methods disclosed may be made without departing from the spirit and scope of the invention, which is defined by the following claims and is not limited in any manner by the foregoing description.