Patent Publication Number: US-2011054436-A1

Title: Method and system for maintaining aseptic conditions in the storage of biologics

Description:
FIELD OF THE TECHNOLOGY 
     The present technology is generally related to maintenance and storage of biologics as it pertains to maintaining aseptic conditions, and more specifically to preventing contamination due to repeated access. The biologics can comprise drugs, cells in suspension or other solutions or fluids intended for aseptic storage and routine access. For example, an aseptic container can store human breast milk for repeated enteral feedings while minimizing the risk of contamination and increasing the shelf life of the milk. 
     BACKGROUND 
     The storage of biological fluids and solutions is routine practice in biomedical applications today. However, shelf-life of these fluids and solutions can be compromised through contamination due to repeated access. Contamination can be minimized by storage of these fluids and solutions in single dose volumes, preventing the potential contamination by eliminating the risks posed by multiple accessing of the aseptic storage container. However, dosage volumes may not be predictable in all instances, and the increase storage space requirements associated with multitudes of single dose containers may not be feasible. 
     The current art lacks a reliable way to allow for the flexibility of dosing regimens and the reduction in storage complexity for biologic fluids and solutions as it relates to their prescription, administration and delivery. Moreover, the art lacks adequate systems and methods for reducing the risks associated with the manipulation, transport, handling, storage and/or repeated access of biologics whose aseptic condition may be sensitive to such actions. A technology addressing this need, or some other related technological deficit, would benefit practitioners. 
     In one aspect of the present invention, a means for storing multi-dose volumes of human breast milk can provide for repeated access of the biological fluid without the risk of contamination and subsequent reduction in shelf life. The discussion of maintenance of aseptic conditions in multi-dose volumes of human breast milk presented in this summary is for illustrative purposes only. Various aspects of the present invention may be more clearly understood and appreciated from a review of the following detailed description of the disclosed embodiments and by reference to the figures and claims. Other aspects, systems, processes, methods, features, advantages, benefits, and objects of the present invention will become apparent to one of ordinary skill in the art upon examination of the following detailed description and the accompanying figures. It is intended that all such aspects, systems, processes, methods, features, advantages, benefits, and objects are to be included within this description, are to be within the scope of the present invention, and are to be protected by the accompanying claims. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1A  is a prospective view of the aseptic container assembly, shown with cap open and main body ready for attachment to fluid transfer component (i.e.—breast pump, etc.) 
         FIG. 1B  is a side view of the same assembly showing section A-A 
         FIG. 1C  is a section view A-A of the assembly shown in  FIG. 1B  showing the assembly with the cap off and the plunger in the topmost position; indicating that the aseptic container is empty. 
         FIG. 2A  is a prospective view of the aseptic container assembly, shown with cap closed; indicating that the aseptic container has been filled with the fluid intended for storage and/or repeated access. 
         FIG. 2B  is a side view of the same assembly showing section B-B 
         FIG. 2C  is a section view B-B of the assembly shown in  FIG. 2B  showing the assembly with the cap on and the plunger in the bottom most position; indicating that the aseptic container is full and showing detail view C. 
         FIG. 2D  is a detail view C of the section view B-B of the assembly shown in  FIG. 2B  showing the assembly with a ball valve in the closed position. Said ball valve is configured such that in the closed position it rests in a sealed position against the top inside surface of the cap, preventing contaminants from entering the aseptic container. 
         FIG. 3A  is a prospective view of the aseptic container assembly showing access by a standard syringe. The syringe is inserted into the container cap such that the tip of the syringe is flush with the ball valve. 
         FIG. 3B  is a side view of said assembly showing section D-D 
         FIG. 3C  is a section view D-D of said assembly, showing the syringe tip fully engaged against the ball plunger, and the plunger in the topmost position; indicating that the aseptic container has been emptied and showing detail view E. 
         FIG. 3D  is a detail view E of section view D-D of the assembly in 
         FIG. 3B  showing the syringe barrel fully engaged against the ball valve, the ball valve spring fully compressed and the syringe barrel tip flush with the inside surfaces of the aseptic container cap; ensuring no outside contaminants can enter the cap exchange interface during repeated access by the syringe. 
         FIG. 4A  is a side view of an alternate embodiment of the aseptic container and showing section F-F and with the assembly cap closed. 
         FIG. 4B  is a section view F-F of the aseptic container assembly in  FIG. 4A  showing the alternate embodiment of the aseptic container full and the duckbill valve and ball valve combination of the cap as indicated by detail view G. 
         FIG. 4C  is a detail view G of the cap assembly with combination valve show in section view F-F of  FIG. 4B . The ball valve is closed such that the outside surface is flush with the inside surface of the cap tip and the duckbill valve is flush with the outside surface of the bottom stem of the ball valve; preventing contamination on two levels. 
         FIG. 4D  is an alternate view of the assembly in  FIG. 4A  showing section view H-H. 
         FIG. 4E  is a section view H-H of the assembly shown in  FIG. 4C  showing an alternate view of the aseptic container cap assembly with combination valve and detail view I. 
         FIG. 4F  is a detail view I of section view H-H showing the ball valve and duckbill valve assembly in the closed position. The ball valve is configured such that is can slidably engage the duckbill valve during repeated access while maintaining the duckbill valve in a closed position; especially under positive pressure, thus preventing the introduction of contaminants through the ball valve when under pressure. 
         FIG. 5A  is a side view of the alternate embodiment shown in  FIG. 4A  as engaged by a syringe barrel during repeated access and showing section view J-J. 
         FIG. 5B  is a section view J-J of the assembly shown in  FIG. 5A  showing the syringe barrel fully engaged with the ball valve, and the duckbill valve open due to evacuation of the aseptic container due to withdrawal of the syringe plunger; allowed only by the full engagement of the ball valve by the syringe barrel tip and as showing detail view K. 
         FIG. 5C  is the detail view K of section view J-J showing the combination valve as fully engaged by the syringe barrel tip and with the duckbill valve open during aspiration, allowing removal of the fluids stored within the aseptic container while preventing introduction of contaminants during withdrawal. 
     
    
    
     DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS 
     The present invention may be understood more readily by reference to the following detailed description of the invention taken in connection with the accompanying drawing figures, which form a part of this disclosure. It is to be understood that this invention is not limited to the specific devices, methods, conditions or parameters described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed invention. Also, as used in the specification including the appended claims, the singular forms “a,” “an,” and “the” include the plural, and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” or “approximately” one particular value and/or to “about” or “approximately” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. 
     Referring now to  FIGS. 1-2 , an aseptic container assembly  10  is shown according to a first example embodiment that supports storage for repeated access while minimizing exposure of a biological agent to contamination. Those skilled in the art having benefit of this disclosure will appreciate that, beyond addressing repeated access of the biologics contained therein and the impact of contamination to the biologics due to said repeated access, the present technology and the aseptic container  10  address further needs in the art, for example providing storage and repeated access finesse even for biological agents that are not susceptible to contamination. 
     The term “contaminate”, as used herein, generally refers to: a foreign or non-sterile material, with resulting impact of limiting the usable life of the biologics stored within the aseptic container. The term “contamination,” as used herein, generally encompasses the act of introducing a foreign or non-sterile material during repeated access of the biologics, with resulting impact of limiting the usable life of the biologics stored within the aseptic container. 
     Those skilled in the art having benefit of this disclosure will appreciate that a biological fluid or other agent maintained in solution (such as, but not limited to; cells in suspension or human breast milk) stored within an aseptic container and intended for repeated access is prone to contamination due to exposure to non-sterile conditions or the introduction of non-sterile materials during said access. While the repeated access of said biologics in standard aseptic containers is commonly conducted using sterile access devices, contamination can still occur due to the lack of proper sealing of the container after said access, or due to the introduction of contamination materials that may be present on the surface of said container during introduction of the access device. 
     Examples of biological agents include; living cells in suspension; therapeutic cells (stem cells, progenitor cells or cells having a capability to differentiate into a specific type of cell); drugs; pharmaceutical agents; one or more pharmacologically active ingredients disposed in a delivery solution; drug carrier systems; biochemicals susceptible to various storage conditions; carbohydrate compounds and materials in solution; and various biological fluids such as, but not limited to, human breast milk, etc., without being exhaustive. 
     The aseptic container  10  comprises a storage body comprised of a generally elongate cylindrical form  12  having a distal enclosed end or base  16 , a proximal open end  13 , and an internal surface  17  extending there through. The body  12  can be constructed of a biocompatible material such as but not limited to silicone rubber, polyurethane, polyethylene, thermoplastic elastomers, or any other suitable polymer or material. The distal enclosed end  16  of the storage body  12  includes a movable member at the end of the lumen  19 . This movable member  19  is also constructed of biocompatible material such as but not limited to silicone rubber, polyurethane, polyethylene, thermoplastic elastomers, or any other suitable polymer or material. The enclosed end may take many forms other than those shown in the figures, including but not limited to; collapsible bag, translational body, pressurized assembly, etc., without being exhaustive. 
     For certain applications, the storage body  12  can be sized for connection to standard collection apparatus for biological fluids such as human breast milk via the open end  13 . The open end can take the form of locking threads, snap connection, etc., without being exhaustive. The geometry of the storage body is sufficient to provide adequate storage volume for the biologic during transfer from the origin into the aseptic container, but can vary depending on application. The section view  FIG. 1C  shows the empty aseptic storage container  10  such that the distal movable member  19  is withdrawn and fully proximal such that the minimum enclosed volume is displayed. 
     The storage body  12  further includes a tethered cap  11  placed adjacent to the storage body  12 , either permanently affixed or attached via some form of connection umbilical  14 . The cap  11  has a large inner and outer diameter than the storage body  12 . The cap  11  is affixed to the storage body  12  such that it can be applied to the proximal open end  13  of the storage body  12  without difficult manipulation. The cap  11  is aligned with the storage body  12  and defines the means for enclosing the biologics within the storage body  12  once the aseptic container  10  is full or ready for storage. The cap  11  includes a means to access the biologics contained within the storage body  12  via a seal  18  on the top of the cap. The seal  18  prevents access of contaminants there through. The cap, as shown in  FIG. 2 , can be integrally connected to the storage body  12  such that it forms a fluid tight assembly  20 . 
     The inner surface  17  defines a sterile, biologic storage space, chamber or reservoir  17 , which contains the biologic during storage and repeated access via the seal  18  and protects the biologic from contamination encountered during access of the biologic through the seal  18 . The seal  18  can be constructed of biocompatible surface contact sealing materials, such as thermoplastic elastomers, silicone, polyisoprene or other appropriate materials that, when pressed against a surface of greater rigidity, provide a fluid tight seal. When accessed, the seal  18  provides for the means to withdraw the biologics from the storage body  12  such that the distal movable member  19  retracts and reduces the total available volume of the aseptic container accordingly. This corresponding change in container volume prevents the formation of internal vacuum during withdraw of the biologic, thereby eliminating the potential for introduction of contaminants due to the need to normalize with ambient conditions. 
       FIG. 2C  is a section view of the capped aseptic container assembly  20  and shows the aseptic container  20  filled to capacity such that the distal movable member  19  is fully distal such that the maximum enclosed volume is displayed.  FIG. 2D  shows a detail view of the section view  2 C for the seal  18 . Proximate the seal  18  are one or more holes, apertures, or passageways  24  through the cap  11  providing entry into the enclosed aseptic container  20  and around the seal  22 . The plurality of holes  24  permits the movement of the biologic between the inner sterile surfaces  17  and the outer cap  11  during access and movement of the seal  22 . 
     Accordingly, fluid in the inner storage body  12  can flow through the holes  24  and the seal  18  and into the intermediate transport vessel  31  and as shown, and hereby referred to as, a needleless syringe format in  FIG. 3 . However, when the nozzle  32  of the needless syringe  31  is inserted into the seal  18  to access the storage biologic, the syringe  31  at least substantially, if not fully, occludes the exit of the seal  18  thereby preventing inadvertent expulsion of the biologic during access as shown in  FIGS. 3C and 3D .  FIG. 3C  is a section view of  FIG. 3B  showing the connection of the needless syringe  31  to the aseptic container  10  via insertion of the nozzle  32  into the seal  18 .  FIG. 3D  is a detail view of the section view in  FIG. 3C  showing the placement of the syringe  31  nozzle  32  within the seal  18 . Additionally, the path through the holes  24  can be opened only upon access with the nozzle  31  such that it has depressed the seal  22  sufficiently to eliminate the fluid tight seal previously maintained prior to access. The seal return  23  is shown compressed such that the seal  22  can be returned to its nominal state upon removal of the nozzle  32 . The seal return can be comprised of biocompatible material such as stainless steel compression springs, shape memory alloys such as nickel titanium, elastomeric polymers or other similar materials. 
       FIGS. 4 and 5  show alternate views of the aseptic container  40  with internal self-penetrating components attached to the seal  18 . In this embodiment, and as shown in the detail view  FIG. 4C  of the section view  FIG. 4B , the seal body  42  includes an asymmetric self penetrating feature  44  that pushes through an integral seal  45  built into the cap  11  aperture  46 . This asymmetric self penetrating feature is shown in the opposing plane in the detail view  FIG. 4E  of the section view  FIG. 4D . In this view, the self penetrating feature is shown across the seal  45 , but such that said seal  45  provides a fluid tight seal against the feature  44  when the seal body  42  is fully engaged with the seal  18  via the seal return component  43 . 
     In  FIG. 5 , the aseptic container assembly  50  is accessed by the needless syringe  31  such that the nozzle  32  is fully engaged with the cap  11  seal  18 .  FIG. 5C  shows a detail view of the section view in  FIG. 5B . This detail view displays the accessed aseptic container assembly  50  such that the nozzle  32  is fully engaged with the seal  18 . In this view, the seal body  42  is depressed such that the integral seal  45  is moved away from the seal body  42  and the penetrating feature  46  is fully within the sterile internal storage space  17  and provides for passage of the biologic container therein past the integral seal  45 , around the asymmetric seal body  42  and into the needless syringe  31 . Similarly to the action shown in  FIG. 3 , the practitioner withdraws the plunger of the syringe  33  to cause the biologic to flow from the aseptic storage container  50  into the needless syringe  31 . To adjust for the change in fluid volume the distal movable member  19  compensates by altering its position or geometry within the storage body  12  to adjust the volume within the storage body  12  to thereby keep the biologic within the sterile storage space  17  without causing the formation of differential pressure such that a vacuum occurs within the storage body  12 , thereby increasing the likelihood of the flow of contaminants into the sterile storage space  17 . 
     While the invention has been described with reference to example embodiments, it will be understood by those skilled in the art that a variety of modifications, additions and deletions are within the scope of the invention, as defined by the following claims.