Abstract:
An apparatus for processing one or more products in need of closure. The apparatus comprises a vessel including an inlet for receiving the one or more products and an outlet for discharging the one or more products under sterile and/or pyrogen free conditions. A device is also adapted for applying the closure to the one or more products in the vessel, along with the optional filling and/or weighing of the products before or after applying the closure. Related apparatuses, systems, and methods are disclosed.

Description:
TECHNICAL FIELD AND BACKGROUND 
       [0001]    This invention relates to a disposable production line for processing, manipulating, manufacturing and/or packaging products or devices under an inert atmosphere, and/or sterile conditions and/or a pyrogen free environment. This invention further relates to U.S. Patent Application Pub. Nos. 2012/0031042 and 2012/0294697 to Zambaux, the disclosures of which are incorporated herein by reference. 
       SUMMARY 
       [0002]    This disclosure may be considered to relate to an apparatus for processing one or more products in need of a closure. The apparatus includes a vessel including an inlet for receiving the one or more products and an outlet for discharging the one or more products under sterile and/or pyrogen free conditions. A device, such as a tool, is adapted for applying the closure to the one or more products in the vessel. 
         [0003]    In one embodiment, the device comprises a sleeve connected to a wall of the vessel, such as the top wall. The sleeve may comprise a flexible sleeve having a rigid portion adapted for applying the closure to at least one product. The rigid portion may be adapted for applying a closure to each of a plurality of products simultaneously. 
         [0004]    The apparatus may further include a platform in the vessel opposite the device for supporting the one or more products, which platform may be connected to a motive device and move from the inlet to the outlet of the vessel. The device may comprise a tool in the form of a press. The press may be positioned in the sleeve, and the vessel may comprise at least one flexible wall (such as part of a flexible bag). 
         [0005]    The apparatus may further include a scale associated with the vessel for weighing the one or more products before or after applying the closure. A platform may be provided for supporting the product or products for being weighed on the scale. A conduit for pressurizing the vessel may also be provided. The apparatus may include a glove attached to the vessel for manipulating one or more of the product, the device, or the closure, and a basket or tray may support a plurality of products in the vessel. The device may be adapted to apply a closure to the plurality of products in a simultaneous fashion while positioned in the basket or tray. 
         [0006]    A further aspect of the disclosure relates to the foregoing system, and further including an apparatus comprising a filler or filling means for filling the product prior to passing the product to the vessel for receiving the closure. 
         [0007]    Still another aspect of the disclosure pertains to an apparatus for processing one or more products. The apparatus comprises a vessel including an inlet for receiving the one or more products and an outlet for discharging the one or more products under sterile and/or pyrogen free conditions. A platform for supporting the one or more products in the vessel is adapted for moving toward the inlet or the outlet of the vessel. A motive device may be provided for moving the platform, which may be connected to a wall of the vessel between the inlet and the outlet. 
         [0008]    A further aspect of the disclosure relates to a method of processing a product. The method comprises applying a closure to the product using a press contained at least partially within a sleeve projecting into a compartment of a vessel under sterile and/or pyrogenic conditions. A further aspect relates to a method of processing a product comprising moving a product on a platform in a compartment of a vessel under sterile or pyrogenic conditions from closer to an inlet of the vessel to closer to an outlet of the vessel. Either method may further include the step of filling the product prior to the step of applying the closure or moving the product. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWING FIGURES 
         [0009]      FIG. 1  is a schematic view of one embodiment of the product processing system; 
           [0010]      FIGS. 2-5  illustrate various examples of isolators for use in the system of  FIG. 1 ; 
           [0011]      FIGS. 6-7  illustrate another example of an isolator for weighing/capping products. 
       
    
    
     DETAILED DESCRIPTION 
       [0012]    A system  10  for processing a product under an inert atmosphere, under sterile conditions, and/or in a pyrogen free environment, is disclosed. The system  10  may include a plurality of isolators, which may be connected to one another to complete the system  10 . In the exemplary embodiment illustrated in  FIG. 1 , the system  10  includes a first transfer isolator  12 , a second transfer isolator  14 , a filling isolator  16 , and a weighing and capping isolator  18 . Each of the isolators  12 ,  14  may include at least one flexible wall, and may be in the form of a flexible and/or disposable vessel, such as a bag. 
         [0013]    With further reference to  FIG. 2 , the first transfer isolator  12  may include at least one inlet  20  and one or more outlets  22 . Each of the inlet(s)  20  and the outlet(s)  22  may comprise a port for sealing with another isolator or other container under a controlled atmosphere, sterile and/or pyrogen free conditions. In addition, the first transfer isolator  12  may include one or more regulating ports  27 , which may be attached to a gas tube  28  that may be used to inflate and/or deflate the first transfer isolator  12 , and/or to introduce a sterile, inert, and/or pyrogen free gas to create a desired atmosphere within the first transfer isolator. These regulating ports  27  and/or gas tubes  28  may be used to control and/or manipulate the pressure within an isolator. 
         [0014]    The first transfer isolator  12  may further include one or more glove ports  24  for allowing access to manipulations of the contents of an interior of the first transfer isolator  12  in a sealed manner. These glove ports  24  may be connected to one or more gloves  25 . The gloves  25  may be located on two or more sides of the isolator, such as on opposite sides, so as to allow for two or more people to work in the isolator at the same time. Each side of the isolator  12  may include upper gloves and lower gloves, so as to allow an operator to work from both a standing and a sitting position. In practice, there may be times when transferring an item from one isolator to another may require picking up an item with a lower glove and moving it into a hand in the upper glove because the upper glove is closer to the outlet (or vice-versa when transferring into an isolator). 
         [0015]    Sterile and/or pyrogen free containers C may be transported in a transfer station (not shown) that may be linked to the inlet  20  of the first transfer isolator  12 . The transfer station may be disposable or non-disposable in nature. Once linked, the system  10  may be considered a closed system, with each isolator or other container being linked by connectors, such as flexible tubes. These connectors may be of the type disclosed in either of U.S. Patent App. Pub. Nos. 2012/0031042 or 2012/0294697. 
         [0016]    The connectors may be closed off by doors  26  on each side of the connector (to initially isolate each section from the other sections and to allow for cleaning and sterilization of the connectors). Once the transfer station is attached, all the doors  26  may be removed. The containers C may then be passed into the first transfer isolator  12  through the inlet  20  and uncapped therein. The uncapped containers may be placed into a tray or basket and the caps may be placed in a different tray or basket. 
         [0017]    As illustrated in  FIG. 2 , the first transfer isolator  12  may have plural outlets  22 . The closure, caps or other pieces for use in assembling the product may be passed through one of the outlets to the second transfer isolator  14 . The products, such as uncapped containers C, may be passed through the second of the two outlets to the filling isolator  16 . 
         [0018]      FIG. 3  illustrates the second transfer isolator  14  in further detail. The second transfer isolator  14  may include one or more inlets  30  and one or more outlets  32 . In the illustrated embodiment, the second transfer isolator  14  includes a single inlet and a single outlet. The second transfer isolator  14  may also include one or more regulating ports  27  and/or gas tubes  28  for regulating the atmosphere within the second transfer isolator  14 . 
         [0019]    In addition, a platform  34  may be included in the second transfer isolator  14  for facilitating movement of items, such as products, within the isolator. The platform  34  may interact with a motive device outside of the isolator for manipulating a position of the platform within the interior of the second transfer isolator  14 . The motive device may include an electronic motor and/or a manual motive device. 
         [0020]    The platform  34  may be connected to the wall of the second transfer isolator  14 , such as by welding, and may be provided with sufficient flexible material to allow for the platform to move within the interior of the isolator. In use, the platform  34  may be moved closer to the inlet  30  to receive items from the first transfer isolator  12 , such as caps removed from the containers C. The platform  34  may then be moved closer to the outlet  32  to allow passage of items, such as uncapped containers, for downstream processing, such as to the weighing and capping isolator  18 . 
         [0021]    One example of a filling isolator  16  is shown in further detail in  FIG. 4 . This particular filling isolator  16  includes an inlet  40  for receiving items, such as from the first transfer isolator  12 . An outlet  42  may also be included in the filling isolator  16 , such as for delivering filled containers to the weighing and capping isolator  18 . The filling isolator  16  may include a dispenser, such as a filling means  46 , for dispensing a product into a container C within the isolator. The filling means  46  may include a needle in communication with a conduit and a source of the substance to be used to fill the container C, and may be similar to that which is disclosed in U.S. Patent App. Pub. No. 2012/0031042. The filling isolator  16  may also include one or more regulating ports  27  and/or gas tubes  28  for regulating the atmosphere within the isolator. 
         [0022]    In addition, the filling isolator  16  may include a platform  44 , which may be moveable within the interior of the isolator. The platform  44  may interact with a motive device as described above for controlling the position of the platform. In practice, a carrier, such as a tray or basket, carrying the uncapped container(s) may be placed on the platform  44 . An actuator may cause the filling means  46  and the platform  44  to align with one another to facilitate filling of the container(s). In the case of the filling isolator including a flexible wall and the filling means  46  is connected to it, this allows for the filling means  46  to be lowered into each container and fill the container C with a given substance. The platform  44  may be automatically shifted according to preset specifications until plural containers C in a particular group are filled. At the end of the filling process, the platform  44  may be manipulated to a position close enough to the outlet  42  so that the filled containers may be passed into the weighing and capping isolator  18 , and then alight as completed containers C′ from the associated outlet. 
         [0023]    The weighing and capping isolator  18  is shown in further detail in  FIGS. 5-7 . This isolator  18  may include two inlets  50   a,    50   b.  The first inlet  50   a  may be utilized for receiving caps from the second transfer isolator  14 , while the second inlet  50   b  may be utilized for receiving filled containers from the filling isolator  16 . The weighing and capping isolator  18  may further include an outlet  52  for removing items from the isolator and/or the system  10 . 
         [0024]    The weighing and capping isolator  18  may be adapted for interacting with a scale  56  for the weighing one or more containers within the isolator, such as filled containers received from the filling isolator  16 . The scale  56  may be external to the interior of the weighing and capping isolator  18 , and may be supported within a well  57  external to the isolator. The well  57  may be included in a frame F supporting the weighing and capping isolator. 
         [0025]    The weighing and capping isolator  18  may further include a cover  54  for interacting with the scale  56 . The cover  54  may form a seal with the wall of the weighing and capping isolator  18  so as to allow for pressure control within the isolator, and to seal the scale outside of an interior of the isolator. The cover  54  may also be made partially or entirely of plastic, such as polyethylene. The cover  54  may further include an opening or recess  54   a,  such as in the center of the cover, with a flexible film that allows for centering of a product or container on the scale  56 . The flexible film may seal the opening while allowing a certain degree of movement of a product or container within the flexible film. 
         [0026]    In addition, the weighing and capping isolator  18  may include a sleeve  58 , which may fully or partially cover a device for applying a closure to the product, such as a tool in the form of a capping mechanism  60  for applying a closure to the container C. The capping mechanism  60  may be in the form of a press or similar device capable of moving within the weighing and capping isolator  18  toward and away from the product, and in a manner such that pressure is applied to the product. In another embodiment, the capping mechanism  60  may be adapted to move both in a vertical direction, up and down within the isolator  18 , as well as in one or more horizontal directions, such that the capping mechanism  60  may move in three dimensions. 
         [0027]    The sleeve  58  may be flexible, so as to allow for movement of the capping mechanism  60  within the isolator  18 . Additionally, the sleeve  58  may function to fully or partially seal the capping mechanism  60  from the interior of the weighing and capping isolator  16 . This may allow the capping mechanism  60  to interact indirectly with one or more items within the weighing and capping isolator  18 , such as containers C, through the sealed sleeve  58 . 
         [0028]    As shown in  FIG. 7 , the sleeve  58  may further include a platform at the end within the interior compartment of the vessel forming the isolator  18 , which platform may comprise capping element  62  adapted to contact one or more containers C. The capping element  62  may include a flat lower surface for directly contacting the caps. In another embodiment, the capping element  62  may include a flexible or malleable surface for molding or at least partially surrounding one or more of the closures or caps on the containers. In a further embodiment, the capping element  62  may include one or more pre-formed recesses for receiving one or more of the caps on the containers within the weighing and capping isolator  18 . 
         [0029]    The sleeve  58  and/or capping mechanism  60  may be positioned above a capping platform  64  within the isolator. The capping platform  64  may be configured to accept a tray or basket of products, such as vials or containers, and then position the containers below the capping mechanism  60 . The platform  64  may include a centering device for ensuring that the tray or basket is centered beneath the sleeve  58  and/or capping mechanism  60 . This centering device may include one or more locators, such as recesses or projections, for interacting with corresponding locators in the tray or basket, such as recesses or projections. Alternately, the centering device may include a recess for receiving the tray or basket or a projection from the tray or basket. 
         [0030]    Additionally, the weighing and capping isolator  18  may further include a secondary outlet  66 . This secondary outlet  66  may be utilized for removal of a single container from the isolator  18 , such as in the case of there being a question about the accuracy of the scale. 
         [0031]    In practice, a filled container C or containers may be weighed to ensure a proper amount of a given substance, such as a pharmaceutical compound, is present. The caps may then be initially placed on the containers, either before or after the containers have been placed in the tray. This initial placement of the cap or closure on the containers may be done by hand, such as by the use of the gloves  25  in the isolator  18 . Placement of the containers in the trays may be done after an individual container has been weighed, or the containers may be placed in the tray or basket and the tray or basket and containers may be weighed together. The tray or basket may be placed on the capping platform  64  either before or after containers have been placed in the tray or basket. Once the tray or basket is properly aligned beneath the sleeve  58 , the capping mechanism  60  may be actuated to contact the caps or closures of the containers and to fully seal and cap the containers. This may be done by pressing the capping mechanism  60  against the tops of the containers to press the closures or caps tightly on the containers. This ensures that each container has been filled with the appropriate weight of a given compound, and that the containers are fully sealed before removal from the controlled environment within the system  10 . 
         [0032]    The foregoing descriptions of several embodiments made according to the disclosure of certain inventive principles herein are presented for purposes of illustration and description. The embodiments described are not intended to be exhaustive or to limit the invention to the precise form disclosed and, in fact, any combination of the components of the disclosed embodiments is contemplated. For example, the cover  54 , scale  56 , and well  57  may be associated with a separate isolator from the isolator capping mechanism  60 . In addition, the sleeve  58  may be made of a non-flexible, telescoping material allowing for the relative movement of the capping mechanism, such as in the vertical direction. Modifications or variations are possible in light of the above teachings. The embodiments described were chosen to provide the best illustration of the principles of the invention and its practical application to thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. All such modifications and variations are within the scope of the invention when interpreted in accordance with the breadth to which it is fairly, legally, and equitably entitled.