Abstract:
A dispensing device comprises a sealed package including a collapsible compartment and an administration assembly. The administration assembly includes a delivery device in fluid communication with a substance within the sealed package. A compression panel collapses the compartment to dispense a substance through the delivery device. Embodiments for a single use dispenser for hypodermic administration of a unit dose of a therapeutic fluid, as well as therapeutic packages and methods for administering therapeutic substances to subjects, are also provided.

Description:
A single-use, unit-dose hypodermic therapeutic delivery device. The device improves upon the packaging conditions of the therapeutic substances, while allowing for efficient and cost effective manufacturing. In particular the device has the advantages of improved packaging, storage, transportation, preparation, reconstitution, and delivery of dry powder vaccines. In addition, the device&#39;s construction allows for convenient destruction after use. 
     FIELD OF THE INVENTION 
     The present invention, in one sense, relates to a dispensing package of a unit dose of therapeutic substance and administration of the therapeutic substance to a patient. More particularly the present invention refers to pre-filled film packages where the package is pierced to deliver its content(s). 
     BACKGROUND OF THE INVENTION 
     Film or foil packages (generally referred here after as “film packages”) are abundant in commercial use for hermetically storing content which is sensitive to environmental condition which can cause its perish. Films can be composed to have superior barrier properties to light, air moisture and other elements encountered in and around the package. State of the art film manufacturing methods allow for combination of several monolayers in a multilayer film each providing complementary properties and qualities to the film. For example aluminum Aluminum-Oxide or Teflon laminates provide superior barrier to moisture and oxygen. Polypropylene or Polyester layer provides goof formability of the film, and PE or EVA outer layers provides excellent heat sealing properties. Thus extreme properties can be incorporated in a multi-layer film without giving up on other important properties. Achieving high barrier wall with injection molded parts (hereafter referred to as molded parts) is more challenging and relatively limited than with film walls. Molded parts are usually made from a single uniform material and where a combination of materials or properties is relatively expensive and complicated to manufacture. Also, while films are produced in a continuous process under uniform constant and controlled conditions which reduce the probability of defects in the product, injection molding cycles involve varying conditions which increase risk of defects in particular if the molded parts involve extreme properties such as very small size or very low wall thickness. Thus molded parts provide inferior barrier properties. Defects in molded parts may include cold weld lines (i.e. a seam between one segment of a part to another which is not a homogenous continuation of the material), a crack of a hole, etc. Thus molded parts provide inferior barrier properties for packaging purposes and therefore are not common in this art. Yet several sophisticated packages, which provide extra functionality, combine molded parts in a film package such that the molded part provides part of the wall of the package and therefore a barrier between the content of the pouch and the surroundings. While providing the extra functionality, the molded part is then the Achilles Heel of the hermetic sealing of the content. 
     U.S. Pat. No. 6,979,316 discloses an auto-injector for rapid delivery of a bolus of injectable medication. In one exemplary the auto-injector comprises a pouch reservoir where a septum is implemented at one end of the pouch for piercing said pouch with a needle. The text describes the septum to be a barrier between content of the pouch and the surrounding. The text does not support the term “septum” any further but it is assumed, based on the common terminology in the art that the inventors refer to a self-sealing compressed rubber component that can be penetrated by a sharp hollow member, such as a needle, to communicate with the content of the pouch. Common rubber materials for this application include silicon. Septums are in common use in filling sites or outlet ports of infusion bags, or other forms of containers for liquid medications. 
     In U.S. Pat. No. 3,554,256 a container for packaging and feeding intravenous fluids which includes a flexible tubular container member having sealed ends and an outlet connector disposed midway between the ends of the container for interconnecting with an intravenous tube. The ends of the container member are adapted to be attached to a support so that the container member can be folded over and its ends attached to the support, whereby the outlet is disposed at the bottom of the container member. At least one other connector is located near one end of the container member to permit an additive to be added to the contents of the container. 
     SUMMARY OF THE INVENTION 
     A variety of embodiments are described which broadly relate to the dispensing of a dose of a substance to a subject. In the description which follows, the term “film” refers to any thin resilient wall of a reservoir, including flexible sheets, laminated sheets or films, monolayer or multilayer, extruded, blow-molded, blown-films or calibrated (rolled) films, metal foils, etc. The term “pouch” refers to any form of reservoir at list partly constructed from films. The terms “pouches”, “blisters”, and “compartments” generally refer to packages comprising flexible walls commonly made from film, foil, extruded, blown, blow molded, stamped, cold formed, or thermoformed components. 
     One embodiment of a device comprises a sealed package that includes a collapsible compartment containing the substance. An administration assembly is joined to the package for relative movement there with. The administration assembly may include a delivery device that is movable from a pre-administration position wherein the delivery device is separated from the substance, to a ready position wherein the delivery device is in fluid communication with the substance. At least one compression panel is associated with a sealed package and movable into an engaged position to collapse the compartment and cause the substance to be dispensed through the delivery device. 
     In certain embodiments a coupler joins the administration assembly to the sealed package, and to this coupler may be a fitting or a portion of a solid body which houses at least a portion of the administration assembly and the sealed package. A gasket seal or the like may be interposed between the administration assembly and the solution. Where the collapsible compartment comprises a multi-layered film wall, the seal may be interposed between these layers. Further, a reinforcement insert may be joined to a wall of the collapsible compartment to provide the backing for the seal as the delivery device is advanced toward the ready position. The delivery device may be operable to puncture a flexible wall to establish fluid communication with the substance. 
     A particular embodiment provides a single use dispenser for hypothermic administration of a unit dose of a therapeutic fluid to a subject and comprises a hermetically sealed package including a collapsible first compartment containing a first therapeutic substance, with the first compartment comprising a first flexible wall. A rigid backing supports the hermetically sealed package and an administration assembly is associated with the hermetically sealed package. The administration assembly includes an elongate needle having a piercing end and for penetrating the flexible wall of the first compartment, and extends from the piercing and toward a delivery end for administering the therapeutic fluid. A needle actuator advances the needle from a pre-administration position, wherein the piercing end is separated from the flexible wall of the first compartment, toward a ready position to cause the proximal end to breach the integrity of the flexible wall and establish communication between the therapeutic substance and the delivery and. A hub carries the needle and may be frictionally captured within the coupler. In one embodiment, the hub is threadedly attached to the coupler such that rotation of the hub relative to the fitting advances the needle from the pre-administration position toward the ready position. 
     The single use dispenser may also include a collapsible second compartment containing a second therapeutic substance and having an associated second flexible wall. Here, a frangible seal is disposed between the first and second compartments and the rigid backing is movably attached relative to the compartments between a flattened state and a folded state wherein the backing collapses the second compartment to cause the frangible seal to rapture such that the first and second therapeutic substances are merged. It should be appreciated that the backing which supports the hermetically sealed package may function to collapse one or both of the compartments, or one or more separate compression panels may be employed for this purpose. Further, the compression panel(s) can be configured to protect the needle when it is in the pre-administration position, and may be movable beyond the engaged state to damage, and prevent further use of, the needle. 
     Also described is a therapeutic package for use in administering a dose of a therapeutic substance to a subject. Such a package broadly comprises first and second sealed compartments having respective first and second walls, with each compartment pre-filled with a respective first and second therapeutic fluid. A frangible seal is disposed between the two compartments. The compartments can be merged by directly pressing with a finger or by a compression panel that is movable between a disengaged state towards an engaged state where the compression panel collapses the second compartment to cause the frangible seal to rapture such that the first and second fluids are merged. 
     A still further embodiment provides a dispenser comprising a film package including a collapsible compartment containing the therapeutic substance, an administration assembly joined to the film package for relative movement there with, and a coupler joining the administration assembly to the film package. The coupler may be attached to either an interior or exterior wall of the film package. 
     A method is also provided for preparing to administer a dose of the therapeutic substance to a patient. According to the method an administration device is provided that includes a sealed package and an administration assembly such as described above. The administration assembly is advanced from the pre-administration position toward the ready position causing the proximal piercing and of the delivery device to breach the integrity of the sealed package and establish fluid communication between the therapeutic substance and the distal delivery end. The sealed package may then be compressed with the compression panel to dispense the therapeutic substance through the distal delivery end. The administration assembly may include a protective covering for the delivery device, whereby advancement from the pre-administration position toward the ready position is initiated upon removal of the protective covering. Advantageously also, a portion of the administration assembly may be rotatable to cause the piercing end to puncture the sealed package. A restorative force may then be applied to return the delivery device to the pre-administration position from the ready position. 
     The present invention further discloses a device comprising a package and an administration assembly. The package and administration assembly can be separately manufactured and then joined at a later manufacturing step or by a user, and thereby reducing manufacturing complexity and providing logistic and operation flexibility. 
     The present invention further discloses a compartment containing a substance. The compartment is integrally made from film such that the boundaries of the compartments are solely defined by said film, and where a dispensing assembly is manipulated to break the integrity of the package and communicate the substance with the dispensing end of the administration device. 
     These and other aspects of the present invention will become more readily appreciated and understood from a consideration of the following detailed description of the preferred embodiments when taken together with the accompanying drawings, in which: 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  demonstrates method for fabricating a device according to the present invention; 
         FIG. 2  demonstrates a preferred embodiment of the present invention; 
         FIG. 3  demonstrates a preferred means for sealing between the needle and the reservoir including a rubber gasket; 
         FIG. 4  demonstrates a preferred means for sealing between the needle and the reservoir using radial sealing to the needle; 
         FIG. 5  demonstrates a preferred means for sealing between the needle and the reservoir comprising a support insert in the reservoir; 
         FIG. 6  demonstrates a preferred means for attaching the fitment to the pouch using an insert with a snap fit; 
         FIG. 7  demonstrates a preferred means for sealing between the needle and the reservoir including an insert with a gasket; 
         FIG. 8  demonstrates an embodiment of the pouch where a gasket is incorporated in the wall of the pouch; 
         FIG. 9  demonstrates another preferred embodiment of the piercing mechanism where the piercing is activated by quarter turn of the needle hub; 
         FIG. 10  demonstrates another preferred embodiment of the present invention where automatic piercing is activated by removing the needle protector; 
         FIG. 11  demonstrates a preferred embodiment of the present invention which comprises safety feature to protect from needle stick injuries; 
         FIG. 12  demonstrates another preferred embodiment of the present invention which comprises means for squeezing the pouch; 
         FIG. 13  demonstrates another preferred embodiment of the present invention which comprises automatic piercing mechanism; 
         FIG. 14  demonstrates another preferred embodiment of the present invention which comprises automatic piercing mechanism; 
         FIG. 15  demonstrates another preferred embodiment of the present invention where the pouch comprises a compartment for topical disinfectant product; 
         FIG. 16  demonstrates another preferred means for attaching the fitment to the pouch; 
         FIG. 17  demonstrates another preferred embodiment of the present invention comprising a self piercing means and needle extraction and retraction mechanism; 
         FIG. 18  provides more details of the embodiment of  FIG. 17 ; 
         FIG. 19  demonstrates an embodiment mostly similar to the embodiment to  FIG. 17  but with a different piecing means; 
         FIG. 20  demonstrates an embodiment mostly similar to the embodiment to  FIGS. 17 and 19  but with a different piecing means; 
         FIG. 21  demonstrates another preferred embodiment of the present invention where the device has a shape of a credit card with folding hinge; 
         FIG. 22  demonstrates an embodiment mostly similar to that of  FIG. 21  but with a different folding hinge; 
         FIG. 23  demonstrates an embodiment mostly similar to the embodiment of  FIG. 22  but with a different detent mechanism as well as a disinfectant package; 
         FIG. 24  demonstrates another preferred embodiment of the present invention mostly similar to the embodiment of  FIG. 21  but where the piercing happens in a different fashion; 
         FIG. 25  demonstrates method for fabricating the pouch; and 
         FIG. 26  demonstrates a further method for fabricating the pouch. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustrations specific embodiments for practicing the invention. The leading digit(s) of the reference numbers in the figures usually correlate to the figure number, with the exception that identical or common components which appear in multiple figures may at times be identified by the same reference numbers. The embodiments illustrated by the figures are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that other embodiments may be utilized and changes may be made without departing from the spirit and scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined only by the appended claims. 
     Referring now to  FIGS. 1   a - 1   g , the steps of fabricating a preferred package  10  of the present invention is demonstrated. Referring to  FIG. 1   a , a portion of a thin film cut to shape and size is demonstrated  11 . The film  11  can be made of mono layer or multi-layer plastic, metal, metal oxides, glass or a combination thereof. Other film materials known in the art are applicable.  FIG. 1   b  demonstrates the film portion  11  after a fitting  12  has been attached to it on a folding line  19 . The fitting  12  is preferably made of plastic material and is attached to the film  11  by one of the means known in the art including heat stake welding, ultrasonic welding, RF welding, hot plate welding, adhesives, or mechanical engagement such as snap feature or pressure fit to a member located of the opposite side of the film  11 .  FIG. 1   c  demonstrates a step in the fabrication of the package  10  where two panels of the film  11  are folded along the folding line  19 . The film  11  adjusts itself to accommodate the rigid fitting along the folding line  19 .  FIG. 1   d  demonstrates a fabrication step of the package  11  where a first compartment  15  is formed by welding a defined area  14  of the film  11  between the two opposite folded sides. The geometry of the welding  14  allows for the film portion  13  around the fitting  12  to naturally blend in with compartment  15 . The welding of the film walls  11  can be made by any of the means know in the art including ultrasonic, RF, heat stake, hot plate, etc. Alternatively the walls can be adhered rather than welded.  FIG. 1   e  demonstrates a subsequent step in the fabrication of the package  11  where the first compartment  15  has been filled and sealed and a second compartment  16  has been formed. The sealing portion  17  between the first compartment  15  and the second compartment  16  is frangible such that under the presence of pressure in at least one of the compartments  15  or  16  the attachment of the opposite walls in designated portion  17  will separate (or rupture) allowing said two compartments to merge, while the perimeter sealing of the compartments  15  and  16  remains tightly sealed. The weaker joint of the films at the frangible seal  17  can be achieved in various ways known in the art including use of different sealing conditions (such as welding temperature, welding pressure, or welding time), apply specific sealing geometry, or selective coating or passivation of the sealing layer.  FIG. 1   f  demonstrates a subsequent step of fabricating the package  11  where the second compartment is sealed resulting in a completely hermetically sealed package. Unlike most of the film packages with fitment which are commercially available, where the fitting is inserted between the film walls which construct the compartment and therefore are in direct contact with the content of the package, the content of compartments  15  and  16  are solely exposed to the film  11  inner layer providing a superior barrier from environmental conditions.  FIG. 1   g  demonstrates a subsequent stage of the fabrication of the device  10  where a dispensing assembly  18  is attached to the fitting  12 . 
     The dispensing assembly, also referred to in this embodiment and others as an administration assembly, moves relative to the sealed package and communicates the content of the package to the target to which the content is ultimately applied. A coupler, such as a fitting or fitment, joins the administration assembly to the sealed package. The administration assembly includes a delivery device, and it comprises a proximal end including at least one mean for communicating the content of the package to the dispensing assembly in a sealed fashion; and a distal end comprising at least one applicator for the particular application of the device. In some embodiments the applicator is a canula or a needle for invasive administration of the contents of the package to a tissue of a subject such as intradermal injection, subcutaneous injection, intramuscular injection or other injection methods known in the art for medical, cosmetic, veterinary, or other commercial dispensing applications. In other embodiments the applicator is a dropper tip or a spray head for topical applications, oral applications, enteral applications, parenteral applications, opthalmological applications, nasal, or ear treatment or other medical, veterinarian, cosmetic, beauty or commercial applications known in the art. In yet other embodiments the applicator is a surface applicator such as a brush, pad, sponge for one of the applications described above. In yet other embodiments the dispensing assembly comprises a connector or a fitting to connect to any of the above applicators or to connect to a tube or a bag to which the content of the package is to be dispensed. Commercial applications include dispensing of glue, paint or dyes or samples of such, chemical agents for diagnostic or titration, glues, or other commercial applications known in the art. It will be obvious to those skilled in the art that dispensing assembly may include plurality of applicators or a replaceable applicator. 
     Referring now to  FIGS. 2   a - 2   g , a preferred embodiment of the present invention is demonstrated.  FIGS. 2   a  and  2   b  show general views at the pre-administration (or rest) position, i.e. the position in which the device is during storage, transportation and until it is used. The pouch  11  has the fashion as demonstrated in  FIG. 1 , and an elongated fitting  12 , broadly a coupler, is attached to the pouch along the folded section of the pouch  19 . A needle protector  21  is accommodated at the distal end of the fitment  12 . The first compartment  15  is separated from the second compartment  16  by a frangible seal  17 .  FIG. 2   c  demonstrates a section view along the section line in  FIG. 2   a , revealing a needle  22  having a distal sharp end to facilitate penetration of the needle to the body of a subject, and a proximal end for piercing the pouch  11  in order to establish fluid communication between the needle  22  and the fluid in the reservoir  15 .  FIG. 2   d  demonstrates the device after the first and the second compartment were merged and its contents mixed such that the fluid in the reservoir  15  is now ready for administration.  FIG. 2   e  demonstrates an enlarged detail view of a portion of  FIG. 2   c . The needle  22  passes through a needle hub  23  which is frictionally held within the fitting  12 . It is to be noted that needle  22  has a sharpened inner end portion  20  for penetrating the of pouch  11  and a sharpened outer end portion for use in administering the drug or vaccine to a subject. 
     A needle protector  21  having a diameter such that it can fit within fitting  12  is, for storage and shipment, lodged with its open end fitting within the open end of fitting  12  and held in position by a combination of friction and an inwardly projecting annular ridge which abuts hub  23 . Needle protector  21  functions as an actuator for advancing the needle from the pre-administration position toward the ready position. Protector includes an outwardly projecting flange  25  to control the movement when preparing to administer the solution by forcing needle to breach the integrity of the pouch&#39;s  11  wall. 
     Referring now to  FIG. 2   f , the device is shown in the ready position after the needle protector  21  was pushed toward the fitting  12  thereby manipulating the proximal sharp point of needle  22  to penetrate the pouch wall  19 . The pierced portion of the wall  19  establishes a fluid tight seal against the needle  22  thus ensuring that the medication flows strictly from the reservoir  15  to the distal end of the needle  22 . Referring now to  FIG. 2   g , following the piercing of the wall  19  the needle protector  21  is removed and can be retained for use as a protective cover over the needle  22  once the injection has been administered. 
     Referring now to  FIGS. 3   a  &amp;  3   b  a further preferred embodiment of the present invention is demonstrated which is mostly similar to the configuration of  FIG. 2  except for the addition of a sealing member in a form of a gasket  31  disposed between the fitting  12  and the pouch&#39;s wall  19  to facilitate the sealing of the needle  22  to the reservoir wall  19 . The gasket  31  is made from a resilient material compatible with the specific application and the manufacturing processes, and in most applications latex or silicone rubbers are adequate. In one embodiment the gasket  31  is compressed either radially or axially or both to increase the compression of the gasket  31  on the needle  22  when the last penetrates thereby improving the sealing. The gasket  31  can be held in position by merely being confined between the pouch wall  19  and the fitting  12 , or alternatively can be attached to either the fitting  12  or the pouch wall  19  by one of the means known in the art.  FIG. 3   a  demonstrates a detail of a section view exposing the piercing arrangement in the rest position.  FIG. 3   b  demonstrates the device after the piercing mechanism has been activated: the needle protector is advanced toward the pouch  11  causing the needle hub to displace toward the hub and the needle  22  to penetrate the gasket  31  and the pouch wall  19 . 
     Referring now to  FIGS. 4   a  &amp;  4   b , another preferred embodiment of the present invention is demonstrated, which is mostly similar to the configuration of  FIG. 2  with the exception that a different sealing mechanism between the needle  22  and the reservoir  15  is implemented. Here, the fitting  12  comprise a narrow section  41  that press fits against the needle  22  in a fluid tight seal fashion. The piercing mechanism is similar to that of the configuration of  FIG. 2 .  FIG. 4   a  demonstrates the rest position, and  FIG. 4   b  demonstrates the pierced position. 
     Referring now to  FIG. 5 , a further preferred embodiment of the present invention is demonstrated in which an annular reinforcement insert  51  supports the inside of the pouch wall  19 , thereby to: a) reduce the tendency of the wall  19  to stretch downwardly during piercing, b) provide a rigid backing for compressing the gasket  31  against fitting  12 , c) provide a protection to the sharp piercing end of the needle from getting in contact with the pouch walls  11 . The insert  51  can be made from thermoplastic material such as polypropylene or polyethylene and is attached to the inside of the wall  19  by one of the suitable means known in the art such as heat welding or gluing. 
       FIG. 6  demonstrates another preferred embodiment where the insert  51  and the fitting  12  are attached to the wall  19  through a mechanical engagement between the fitting  121  and the insert  51  through the wall  19 , potentially avoiding the direct attachment between the fitting and the wall  19  or the insert  51  and the wall  19 . A protrusion of the insert  51  comprises a snap feature  61 , in the form of a lateral radial ridge, that is forced into a reciprocal recess with a radial lateral groove  62  in the fitment  12 . 
       FIG. 7  demonstrates another preferred sealing between the needle  22  and the reservoir  15  where a gasket  31  is accommodated between the insert  51  and the inside of the wall  19 . 
       FIG. 8  demonstrates a further preferred embodiment of the pouch of the present invention where the gasket  31  is implemented between the layers of the film wall  19 . 
     Referring now to  FIG. 9   a - 9   d , a further preferred embodiment is demonstrated where the piercing of the pouch  11  is due to a quarter turn of the needle hub  23  rather than pushing inward as it was in previous configurations of  FIGS. 2 to 8 .  FIG. 9   a  demonstrates the rest position of the device  90 . The needle hub comprises lateral protrusions  91  for facilitating the turning action with a finger and thumb.  FIG. 9   b  demonstrates the device  90  when the pouch is pierced and the device is in a ready state for administration. After merging compartment  16  to compartment  15  and mixing their contents, the hub  23  is turned a quarter turn clockwise to pierce the reservoir wall  19 , and thereafter the needle protector  21  is removed making the device ready for administration.  FIG. 9   c  demonstrates a detailed section view of the piercing mechanism of the device  90  at the rest position. The hub  23  comprises an internal threaded bore  92 , engaged with external threads  93  on the fitting  12 .  FIG. 9   d  demonstrates the same view as  FIG. 9   c  after the hub  23  has been turned clockwise, causing the hub  23  to travel axially toward the pouch  11  and the needle  22  to pierce the pouch wall  19 . 
       FIGS. 10   a  &amp;  10   b  demonstrate another preferred embodiment of the present invention comprising an automatic piercing mechanism which is activated at the removal of the protector  21 . Referring to  FIG. 10   a , a compressed coil spring  101  is accommodated between the distal end of the fitting  12  and the needle hub  23  biasing the needle hub  23  toward the pouch  11 , yet the hub is retained in a offset position from the pouch by detent arms  102 . Detent arms  102  have the form of cantilever springs and their tapered contact surface with the hub  23  apply an outward radial force on the arms  102  to disengage from the hub  23 . The detent arms  102  are counter-forced inward by the protector  21 . Referring to  FIG. 10   b , as the protector  23  is removed the cantilever arms  102  are free to move outward by the force applied by the hub  23 , thereby disengaging from the hub  23 . The hub  23 , under the force of the spring  101  advances toward the pouch  11  causing the needle to pierce the wall  19 . 
       FIGS. 11   a - 11   e  demonstrate a further preferred embodiment of the present invention comprising a needle stick safety feature and automatic piercing feature.  FIG. 11   a  demonstrates a perspective view of the device comprising the pouch  11 , a fitment  12  having a cover  112  with a mostly longitudinal slot  113  in which a slider knob  111  is disposed and can be operated to travel along said slot to manipulate the needle to the administration extended position, and for piercing the wall of the pouch. Protrusions  118  of the knob  111  lean against surface  112  preventing the knob from rotating when operated, except when the protrusions  118  reach the broadening in the slot  117 . In  FIG. 11   a  the device  110  is demonstrated in its rest position in which the needle is confined in the fitting  12 . A tamper evident member  114 , for indicating whether the device has been previously tampered with, retains the knob  111  in the rest position. Referring now to  FIG. 11   b  a cross-section of the device  110  is shown in the rest position. The fitting  12  comprises a pouch piercing hub  114  and an elongated body in which the needle  22  is disposed, its distal end accommodated in an opening  115  of the fitting  12  and it is attached to the slider  111  next to a bend in the needle  22 , while its proximal (piercing end) is free. 
     Referring now to  FIG. 11   c  the device  110  is demonstrated at an intermediate instant of the activation action, it being understood at this point that one or more of the compartments, e.g., compartment  16 , has been depressed to merge their contents. After compartment  16  was merged with compartment  15 , and the fluids in the extended compartment  115  were mixed and ready for administration, the tamper evident piece  114  is broken-off and the knob is operated to advance the needle  22  to extend from the fitting  12 . The operation of the knob  111  is achieved by placing the finger on the pad  116 , the thumb on slider knob  111  and squeezing the knob  111  forward. In return, the knob  111  slides forward until it hits the end of the slot  113 , at which point protrusions  118  are aligned with the broadening zone  117  of the slot  113 . Referring now to  FIG. 11   d , the end position of the knob  111  outward operation is demonstrated in which, under continuation of squeezing the knob forward, the knob  111  tilts counterclockwise thereby causing the needle to bend and the proximal end of the needle to penetrate the piercing hub  114  and pierce the pouch  111 . At this position the protrusions  118  are engaged with the broadening zone  117  of the slot  113 , holding the knob (and the needle) from moving along the slot  113  during administration. The knob  111  is detained in the rotated position by a pair of detent protrusions (not shown) that engage in the slot  113  at the end of the knob rotation. In a further configuration the force that the needle applies to the knob due to its bending is in a direction which causes a counterclockwise torque to the knob. Such arrangement are some times referred to a self locking mechanism, toggle mechanism, or over-center mechanism. At the end of the administration the knob  111  is manipulated back to the original position thereby disconnecting the needle  22  from the reservoir  15  and hiding the distal end of the needle  22  in the fitting  12 . 
     In a further embodiment a compressed spring is disposed in the fitting  12  along its longitudinal direction such that it biases the knob  111  to the rest position, causing the knob  111  to return to the backward position as soon as the knob  111  has been rotated back from the administration position. 
       FIG. 11   e  demonstrates the position of the device after the knob has been retracted to the rear most position. As the tamper evident  114  is now absent, the knob  111  retracts to a further backward position than the rest position. At this position the distal end of the needle  22  disengages from the opening  115  such that any subsequent attempt to operate the knob to the extended position of the needle, is prevented as the needle hits the wall of the fitting  12 . In one embodiment a constant tension on the needle  22  ensures that the needle  22  tip will be removed sidewards from the opening  115 . 
     Referring now to  FIGS. 12   a - 12   e , a further preferred embodiment of the present invention is demonstrated where a device for facilitating the squeezing of the reservoir for administration is provided.  FIG. 12   a  demonstrates a device  120  at the rest position, comprising a pouch  11  which holds a hermetically sealed reservoir  15 , and a fitting  12  attached to said pouch  11  confining the pouch&#39;s piercing hub (not shown) and a proximal end of a needle  22  for piercing said pouch. The device further comprises a protector having a core  123  firmly connected to the fitting  12  and two rotatable hoods  122 , connected to the core  123  by living hinges  126 , which cover the distal end of the needle, thus forming a protection from accidental needle stick injuries. In each of the hoods  122  a groove  125  defines a cantilever surface  124  which at a later position will be used as a compression panel for squeezing the reservoir  15  to cause the fluid in said reservoir  15  to expel.  FIG. 12   b  demonstrates a section view of the device  120  at the rest position. The needle  22  is positioned such that the proximal end of the needle is offset from the gasket  31 . The needle hub  23  can be reached through opening  127  at the base of the hoods  122  to operate the needle hub  23  to pierce the pouch. Refer now to  FIG. 12   c  which demonstrates a variation on the needle hub  23  which here comprises two vertical arms that prevent the hoods  122  from opening unless the hub  23  has been manipulated down to pierce the pouch, thereby determining the sequence in which the device is to be operated. In  FIG. 12   d , the device  120  is demonstrated at intermediate instant of opening the hoods  122  in a disengaged state. Where the needle hub  23  has not been operated at an earlier stage to pierce the pouch  11 , a clear access to the needle hub  23  allows making the piercing operation at this stage. Referring now to  FIG. 12   e , a section view demonstrates the device  120  ready for administration. The hoods  122  has been fully opened such that the compression panels  124  are leaning against the reservoir  15  in an engaged state and the internal side of the cantilever surfaces  124  are used as squeezing pads. Squeezing the reservoir  15  with the compression panels allows convenient and efficient means for completely emptying the reservoir  15 , especially if the last has a surface larger than the finger pads  128 . Upon completing the administration the hoods are returned to the rest position to protect for accidental needle injuries. The current embodiment provides improved needle-sticks safety compared with embodiments where a protector is replaced on the needle after use in the axial direction of the needle. In this embodiment the protector panels are pushed from the sides in a manner that the fingers are not exposed to needle sticks 
     In one embodiment a tamper evident feature, showing whether the device has been previously tampered with, needs to be manipulated in order to open the hoods  122 . In another embodiment a tamper evident feature is manipulated by opening the hoods  122 . In a further embodiment a tamper evident feature needs to be manipulated in order to operate the hub  23  to pierce the pouch  11 . In another embodiment the operation of the hub  23  to pierce the pouch  11  manipulates a tamper evident feature. In yet another embodiment a lock feature permanently locks the hoods together when those are returned to the rest position after administration providing an auto-disable feature preventing reuse of the device. 
     Referring now to  FIGS. 13   a - 13   f , a further preferred embodiment is demonstrated which is mostly similar to the embodiment  120  of  FIG. 12 , with the exception that an automatic piercing mechanism is incorporated in the needle protector.  FIG. 13   a , and its enlarged detail view in  FIG. 13   b , demonstrate the device  130  in the rest position A cylindrical sleeve  131  is accommodated concentric with the needle  22 , and spaced apart from needle hub  23 . The sleeve  131  is connected to two joint arms  132  at one end of the joint arms. The other end of the joint arms  132  are connected to the hoods  122 , and at the rest positioned the arms are folded and confined between the sleeve  131  and the hoods  122 .  FIG. 13   c , and its enlarged detail view in  FIG. 13   d , demonstrate the device  130  at intermediate instant of opening the hoods  122 . The end of the arms  132  that are connected to the hoods  122  are pulled out with the hoods, causing the sleeve  131  to move toward, and get in contact with, the needle hub  23 .  FIG. 13   e , and its enlarged detail view  13   f , demonstrate a subsequent instant of opening the hoods  122 . The arms  132  continue to pull the sleeve  131  down as the hoods continue to open, and as a consequence the sleeve displaces the hub  23  toward the pouch  11  causing the needle  22  to pierce the wall  19 . 
       FIGS. 14   a - 14   i  demonstrate a further preferred embodiment  140  of the present invention.  FIG. 14   a  demonstrates a general view of the device  140  at a pre-use configuration. The film  11  that constitutes the pouch continues beyond the piercing hub to cover and hermetically seal over the needle protector, such that the entire device is hermetically sealed and the protector can not just be pulled of from the device  140 . A slit  147  in the film marks the future point of breaking-off the protector and part of the film from the device  140 .  FIG. 14   b  demonstrates the piercing hub  141  and the protector  142 , which confine the needle (not shown), prior to introducing to the pouch  11 . The piercing hub  141  and the protector base  142  share a common profile terminating by a sharp edge  143 .  FIG. 14   c  demonstrates an exploded view of the assembly of  FIG. 14   b . The needle  22 , and the needle hub  23  are now visible. The needle hub  23  comprises an external thread section  144  that engages with an internal thread section of the piercing hub  141 , and a flange section  145  that engages with the needle protector  142  when the last in mounted on the needle hub  23 .  FIG. 14   d  demonstrates the device  140  when the protector and the section of the pouch film that cover it are turned a quarter turn counterclockwise. Because of the common sharp edge of the protector  142  base and the piercing hub  141 , together with the slit  147  in the film in front of the commons sharp edge  143 , as soon as the protector starts turning the film is completely sheared separating the needle protector  142  from the rest of the device  140 . In  FIG. 14   e , after the film package has been sheared off by the quarter turn action, the protector can now be removed. 
       FIG. 14   f  demonstrates the device in the rest position again providing orientation for the following section views.  FIG. 14   g  orients for the detail view of  FIG. 14   h . The thread section  144  of the needle hub  23  is engaged with the internal thread  146  of the fitting  141  such that when the needle hub is rotated in a counterclockwise direction the needle hub  23  will advance toward the pouch  11 . The flange section  145  of the needle hub  23  is engaged with needle protector base  152  such that turning the protector around the needle  22  axis will turn the needle hub along with it, while the needle hub  22  is free to move outward from the protector base  152  along the needle  22  axis. Thus as the protector  21  is turned a quarter turn counterclockwise to shear the film package the needle  22  will advance toward the pouch  11 .  FIG. 14   h  further shows a thin membrane that seals the reservoir  15 .  FIG. 14   i  shows a section view of the same configuration as in  FIG. 14   d , after the protector  21  has been turned a quarter turn in a counterclockwise direction from the rest position. The turn of the protector  21  caused the needle hub  23  to turn and advance out of the protector base  152  and toward the pouch  11  causing the proximal needle end to pierce the membrane  148 . 
       FIGS. 15   a - 15   b  demonstrate a further preferred configuration of the present invention which comprises a compartment for disinfectant substance for disinfecting the skin area at the injection site. The pouch comprises a dedicated slit  152  for concentrating the shear forces when opening the disinfectant compartment  151 . The disinfectant compartment  151  may contain a liquid, a gel, or other forms of disinfectant ingredients. The pouch may further contain a gauze, a sponge, or any other absorbing matrix known in the art that can contain the disinfectant fluid and facilitate the application to the skin at the injection site. In a further embodiment the arrangement is such that the essential steps for preparing the device for administration are conditioned by or are interfered by first utilizing or at least removing or opening the disinfectant compartment  151 . 
       FIGS. 16   a - 16   i  demonstrate a further preferred embodiment where the fitting is accommodated on a welded seam of the pouch.  FIG. 16   a  demonstrates a section view for orientation of the following section views.  FIG. 16   b  demonstrates the rest position. The fitting  12  is mechanically engaged with an insert  51  through the wall of the pouch  11 . The needle hub  23  is accommodated in a vertical slot  153  in the fitting  12 , such that the needle is offset from the seam line of the pouch  11  and is aligned with a conduit  151  in the insert  51 . Referring to  FIG. 16   c , when the needle hub is advanced in the slot  153  toward the pouch, the needle  22  pierces the wall of the pouch  19 . 
     Referring now to  FIGS. 17   a - 17   e , a further preferred embodiment of the present invention is demonstrated.  FIG. 17   a  shows the device  170  in a perspective view. The device  170  comprises a housing  171  and a sliding knob  172  accommodated in sliding grooves (not shown) in the housing  171 . The package  11  is accommodated on the top surface of the housing  11  and comprises a first compartment  15  and a second compartment  16 , separated by a rupturable seal  17  (not shown). The housing  171  conceals a needle assembly which can be extended through opening  173  when activating the device  170 . The sliding knob  172  comprises two sets of two teeth  174  and  175  symmetrically disposed along the front edge of the knob  172 . It can be appreciated that in this Figure and in the following  FIGS. 18 ,  19 , and  20 , the housing acts as the coupler and the sliding knob acts as the actuator. 
       FIG. 17   b  demonstrates a top view of the device  170 . The view provides three section lines for orientation of the subsequent section views. Two sets of two openings, symmetrically disposed in the top of the housing  176  and  177  are designated to accept teeth  175  and  174  respectively, when the knob is advanced to a forward position where said teeth and said openings align. 
       FIG. 17   c  demonstrates a longitudinal section cut of the device  170  at the rest position in proximity to the side wall of the housing  171 . Note that in this Figure and the following section views  FIGS. 17   d  and  e , the knob  172  is shown in its entirety and not sectioned, to better demonstrate the details of this part and their interaction with the device  170 . The knob  172  comprise a first surface  172 ′ in parallel and in contact with the top surface of the housing  171  and an inclined surface  172 ″ (hereafter “compression panel”) in the front of the knob on which the teeth  174 ,  175  are disposed. The ends of teeth  174  are sitting against the upper surface of the housing  174 . The knob  172  further comprises two vertical ribs  177 , engaged in longitudinal grooves in the top of housing  171 , each rib  177  comprises a lateral protruding pivot  179 , perpendicular to said rib  177 , and a latch  178  provided by a notch in the rib  177 . The pivot  179  contacts the inside of the upper wall of the housing  171 . Thus, in the rest position, the knob  172  is constrained to longitudinal movement by the engagement of the ribs  171  in the said grooves, while the rotation of the knob  172  around the pivot  179  is prevented by the three vertical contact points of the knob  172  with the top surface of the housing  171 . A meniscus  185  in the side wall of the housing  171  defines the forward end position of the pivot  179  when the knob  172  is slid forward, at which position the teeth  174  will align with opening  177  allowing the knob  172  to rotate. 
     Referring now to  FIG. 17   d  a longitudinal section view along the symmetric line of the device  170  in the rest position is demonstrated. A needle  22 , connected to a needle hub  23 , are disposed in the housing  171  such that they can be moved along the longitudinal direction of the housing  171 . The needle  22  is accommodated in a slit in the needle hub  23  and is connected by one of the means known in the art such as press fit or glue. A spring  181  is disposed between the housing  171  and the needle hub  23 , biasing the last to the backside of the housing  171 . The needle  22  comprises a sharp distal end  22 ′ for penetrating a tissue of a subject, accommodated in an opening portion of the housing  173 , and a sharp proximal end  22 ″ at the end of a hooked section of the needle  22  for piercing the compartment  15 . The package  11  comprises a first compartment  15  and a second compartment  16  defined between two opposite film walls, and separated by a rupturable welded portion between said walls, and is attached to the front section of the upper wall of the housing  171 . The package  11  is attached to the housing  171  by one of the means known in the art including, welding, gluing, mechanical fit, adhesive layer of the film, etc. The first compartment  15  comprises a well  186  extending through an opening in the upper wall of the housing  171  to the inner side of the housing  171 . A co annular cylinder member  187  is disposed in the well to improve the sealing against the needle  22  when it pierces the wall of the compartment  15 . The hub  23  comprises a detent tooth  182  which is engaged with the latch  178  of the knob  172 , such that when the knob  172  is moved along the housing  171  the needle hub  23  and the needle  22  will be traveling along with it. 
     Referring to  FIG. 17   e , a combined section view of the device  170  is demonstrated. The needle hub  23  further comprises a snap arm  183  aligned, and in an offset position from opening  176 , which comprises an inward protrusion  184  for latching snap arm  183  when the needle hub  23  travels to its forward position. 
       FIGS. 18   a - 18   e  demonstrate embodiment  170  of  FIG. 17  in the ready position. After the compartments  15  and  16  were merged and mixed by pressing and mashing the wall of the package  11  with a finger, the knob  172  is forced by pushing forward the compression panel  172 ″ with a finger to the forward position.  FIG. 18   a  provides a general view of the device  170  with the needle  22  now extending from the housing  171  through opening  173 . Normally at this position the needle is inserted to a target tissue of a patient, which is not shown here.  FIG. 18   b  demonstrates a top view of the device  170  providing orientation for the subsequent section views. The grooves  188  in the upper wall of the housing in which the ribs  177  (not shown) of the knob  172  engage, are now visible. A widening portion of the groove  188  allows clearance for the pivots  179  to pass through the wall into the housing  171  during the assembly process. 
     Referring to  FIG. 18   c , at the front position of the knob  172 , the teeth  174  of the knob  172  aligns with opening  177 , such that forcing the second portion of the knob  172 ″ further forward or downward will cause the knob to rotate counterclockwise. 
     Referring now to  FIG. 18   d , the proximal end of the needle  22 ″ pierced the wall of compartment  15  establishing fluid communication between the fluid in said compartment and the distal end of the needle  22 ′. The sealing member  187  provides for an improved sealing between the needle and the compartment&#39;s  15  wall. The sealing member can be made from rubber materials such as silicone or polyurethane rubber, or a soft plastic material such as PE, a PE/EVA compound, etc. It will be obvious to those skilled in the art that the fluid tight sealing of the needle  22  to the wall  11  can be accomplished by other means. In one embodiments the composition of the actual wall of the package  11  is such that it provides good sealing. Such wall will preferably have a layer of soft thermoplastic such as PE, EVA, Surlin (Dupont) etc. In other embodiment the sealing member is accommodated externally to the package  11  wall. In other embodiments the sealing member is provided by an inward extension of the upper wall of the housing  171 . Referring back to  FIG. 18   d , by continuing to force the compression panel  172 ″ forward (or downward), compartment  15  is depressed by causing the content of compartment  15  to expel through the needle  22  (i.e. the “administration” of the fluid), until the compartment is completely squeezed. 
     Referring now to  FIG. 18   e , as the knob  172  reaches the front most position, the snap arms  183  latch with the protrusion  184  of the opening  176  in the upper wall of the housing  171 . Due to its rocker construction, as the knob  172  is rotated to squeeze the compartment  15 , the latch  178  of the knob is removed from detent tooth  182 , thereby disengaging the knob  172  from the needle hub  172 . Thereafter, and for the duration of the administration, the needle hub  23  is held in the front position due to the engagement of snap arm  183  and protrusion  184 , preventing the spring from pushing the needle hub  23  back in. During the rotation of the knob  172 , teeth  175  penetrate through openings  176  and contact snap arm  183  pushing them down toward disengagement of protrusions  184 , such that as soon as the administration is completed, the snap arms  183  disengage from protrusions  184 , the hub  23  snaps to the backward most position drawing the needle back into the housing. 
       FIG. 18   f  demonstrates the discard position of the device  170 . The hub  23  is now retracted to a position where it can not reengage with the knob  172 , preventing reuse of the device  170 , or abuse of residual substance. In one embodiment the knob can not be rotated back from the counterclockwise end position thereby preventing reach to the package  11 , thereby preventing potential exposure or abuse of the substance. 
     Referring to  FIGS. 19   a - 19   e , a further preferred embodiment of the present invention is demonstrated which is mostly similar to embodiment of  FIGS. 17 and 18 , but for a different method of piercing the package  11 . The general operation and function of the knob  172  is similar to that of  FIG. 17  and therefore will only be briefly described.  FIG. 19   a  demonstrates a general view of the device  190 . A U-shape groove  194  in the upper wall of the housing  191  defines a cantilever portion  195  to which the package  11  is attached.  FIG. 19   b  provides a top view of the device  190  for orientation of the section views in subsequent Figures. 
       FIG. 19   c  demonstrates a section of the device  190  in the rest position. The first compartment  15  comprises a well  186  that extends through an opening in the upper wall of the housing  191 . The proximal end of the needle  22 ″ terminates with a vertical section. 
       FIG. 19   d  demonstrates the device after the second compartment  16  has been merged to the first compartment  15 , and the knob  172  has been moved to the forward position, by pushing on the compression panel  172 ″ forward with a finger. The proximal end of the needle is now aligned with the well  186  of compartment  15 . 
     Referring now to  FIG. 19   d , by further pushing the compression panel  172 ″ forward (or downward), compartment  15  is depressed and as a result causes the cantilever surface  195  to bend down to a point that the proximal end of the needle  22 ″ pierces the wall of compartment  15 , establishing fluid communication between the content of compartment  15  and the distal end of the needle  22 ′. 
     Referring now to  FIG. 20  a further preferred embodiment  200  is demonstrated. The device  200  is mostly similar to the device  190  of  FIG. 19  but for the different piercing means. The device  200  is demonstrated in the administration position. A u cut in the bottom wall of the housing  201  defines a cantilever section  202 . To administer the content of compartment  15  one finger presses the compression panel  172 ″ while another finger provides for an opposite force on the cantilever section  202 , such that the cantilever section  202  bends in and forces the proximal end of the needle  22 ″ to bend and pierce the wall of the first compartment  15 . A sealing member  205  enhances the sealing of the wall of the well  186  of compartment  15 . The sealing member  205  can be made of soft thermoplastic or rubber. 
     Referring now to  FIGS. 21   a - 21   h , a further preferred embodiment of the present invention is demonstrated. Referring to  FIG. 21   a  a perspective view is showing the upper side of the device  210 , shown in the rest position. The device  210  comprises a mostly thin and flat body  211  with a general shape of a credit card divided into a first compression panel  215  and a second compression panel  216  (hereafter sometimes referred to as “panel” or “panels”), mostly similar in size to the first panel  215 , by a living hinge section  212 . The package  11  is attached to the first panel  215 . Referring now to  FIG. 21   b  a perspective view of the under side of the device  210  is demonstrated in the rest position. A needle  22  and a hub  23  assembly is accommodated in a longitudinal recess  213  that extends between the first panel  215  and the second panel  216 , providing clearance for the hub  23  to slide toward the first panel  215 . The second panel  216  comprises a slot  214  for accommodating the distal end of the needle (not seen), providing protection to the needle from being damaged prior to use, as well as from sticking injuries from the needle. It can be appreciated, then, from this embodiment that the hub  23  acts as the needle actuator. In fact, in the various embodiments described herein, the actuator can be considered as any pieces which, collectively or separately, function to advance at least a portion of the administration assembly (or particularly, at least a portion of the delivery device) from the pre-administration position towards the ready position. It can also be appreciated that in this Figure and in the following Figures the flat body  211  acts as the coupler. 
     In one embodiment a label at least partially covers the lower surface of the first and second panels  215 , 216 . In one embodiment the label is at least partially removable. In one embodiment said removable section protects the needle during storage and is removed to expose the needle  22  prior to administration. In one embodiment said removable section of said label prevents access to the needle hub  23 , and by removing said peelable section the hub  23  can be manipulated to move toward the first panel  215 . In one embodiment said removable section of said label bridges between the first panel  215  and the second panel  216 , over the hinge  212  therefore preventing the body  211  from folding, and whereby removing said removable section allows for the body  211  to easily fold. In one embodiment a non-removable section of said label retains the hub  23  in the slot  213 . 
     Referring now to  FIG. 21   c , a longitudinal section view is demonstrated along the symmetry line of the device  210  at the rest position as marked in  FIG. 21   a . The first compartment  15  of the package  11  comprises a well  186  accommodated in a recess in the first compression panel  215 . The proximal end of the needle  22 ″ is accommodated in a horizontal bore  217  connecting the slot  213  and the well  186 , such that the sharp tip of the proximal end  22 ″ is spaced apart from said well  186 . In some configurations the content of the second compartment  16  is powder that needs to be mixed and dissolved with a diluent in the first compartment  115  prior to being administrated. To prevent remaining particles of said powder from reaching the needle  22 , the well  186  is capped with a filter  218  such as nonwoven filter attached the wall of the first compartment  FIG. 21   d  demonstrates a section view along the line marked in  FIG. 21   b . The hub  23  is engaged with both compression panels  215 , 216  by an undercut such that the hub is limited to move in the longitudinal direction of the body  211 , preventing the panels from folding along the hinge  212 . 
     Referring to  FIG. 21   e , a section view of the device  210  is demonstrated at the initial activation position. Compartment  16  has been merged into compartment  15  by separating the frangible weld line  17 . The hub  23  has then been pushed toward the first panel  215  causing the proximal end of the needle  22 ″ to pierce the wall of the well  186  of compartment  15 , thereby establishing fluid communication between the content of compartment  15  and the distal end of the needle  22 ′. The hub is now disengaged from the slot in the second panel  216  allowing the body  211  to be folded i.e. the second panel  216  to be folded over compression panel  215  or vice versa. 
     Referring now to  FIG. 21   f  the administration position is demonstrated where the second panel  216  is folded over the first panel  215  thereby depressing compartment  15  and causing the content of said compartment to expel and to be administered through the needle  22 , to a target tissue of a subject (not shown). By folding the second panel  216  the distal end of the needle  22 ′ is exposed and allows for penetration to a tissue. 
     By small variation in the embodiment of the device  210  the order of the activation steps described above can be switched over. In one embodiment the slot  213  in the second panel  216  does not have the undercut structure as demonstrated in  FIG. 21   d  and the second panel  216  folding is not constrained by the hub  23 . Therefore the second panel can be first folded over the first panel  215  and only then after the well hub is displaced to pierce the well  186 . 
     Referring to  FIG. 21   g , the discarding position of the device  210  is demonstrated. After completing the administration, the second compression panel  216  is rotated back 180 degrees around the hinge  212  to the opposite folded position of  FIG. 21   f , and by doing so folding and destroying the needle  22 . In one embodiment a mechanical latch retains the device in this position, thus providing an auto-disable mechanism for preventing reuse of the device, as well as preventing possible accidental needle sticks after use. 
       FIG. 21   h  demonstrates an enhancement which furnishes the hinge  212  with a toggle like action in a fashion commonly implemented in cosmetic or other flip-top liquid-container closures. Elastic straps  219  are bridging between the first panel  215  and the second panel  216  of the body  211 , in an offset position to the folding axis of hinge  212 , such that the straps  219  are stretched in all the intermediate rotational positions between the end positions, and therefore biasing the second flap to one of the end positions demonstrated in the preceding figures. The toggle action may simplify the user&#39;s action of folding the second panel  216 . 
     In a further embodiment the device  210  comprises a mechanism for causing automatic piercing of the reservoir when the compression panel is folded over similar to the mechanism disclosed in  FIG. 13 . 
     In one embodiment a rubber septum in a form of a sleeve is inserted into the section of the pouch that accepts the proximal end of the needle, to improve the sealing between the needle and the reservoir. 
     Referring to  FIGS. 22   a  &amp;  22   b  a further preferred embodiment is demonstrated mostly similar to the embodiment of  FIG. 21 , but for the hinge connecting between the first panel  215  and the second panel  216 . Panels  215  and  216  are now fabricated as separated bodies, and are connected through a film layer that extends over a gap between the two panels, forming a live hinge  222 . In one embodiment said film is an extension of one of the walls of package  11 . 
     Referring to  FIG. 23  a similar device to devices  210  and  220  of  FIGS. 21 and 22  respectively is demonstrated. A pouch  231  comprises an adhesive back is attached to the lower side of panels  215  and  216  preventing the body from folding. In one embodiment the pouch contains a disinfectant substance that needs to be applied to the area where the needle is to stick. The disinfectant substance can be in a form of liquid, gel, paste, loose in the pouch or absorbed in an absorbent matrix such as gauze. By removing the disinfectant pouch the hub can be operated and the second panel can be folded, thereby establishing a critical constrain between using the disinfectant substance and administration the device to a subject. 
       FIGS. 24   a  &amp;  24   b  demonstrate a further preferred embodiment of the present invention in which the first compartment  15  does not comprise a well and therefore is simpler to manufacture and assemble to the device  240 . The package  11  is attached to an inclined surface relative to the needle  22  and the needle bore  217  such that the needle penetrates the package in an angle. It will be obvious to those skilled in the art that rather than positioning the package on an inclined surface the proximal end of the needle  22 ″ can be guided in a shoot in the first panel  215 , such that during the displacement of the hub  23 , it will bend from a direction parallel to the wall of the package to an angle in which it will penetrate the package.  FIG. 24   b  demonstrates how the finished package is assembled to the device assembly. The attachment of the package  11  in simple manner to the external wall of the mechanical device as is true for embodiment  17  to  24  provides an advantageous means of manufacturing as the package  11  can thus fit pharmaceutical packaging machinery, and be manufactured faster and less expensively. The mechanical device on the other hand can be manufactured in a separate line or a separate facility. The package and the mechanical device can be then integrated in a third facility, or just prior to use, providing better manufacturing, storage, and logistic flexibility. 
     Referring to  FIGS. 25   a - 25   d , a method for producing a two compartment package is demonstrated. Referring to  FIG. 25   a , prior to filling, the seams of the two major walls are welded together except for opening areas which are left open for filling the compartments. The frangible seal  17  is welded usually at a lower temperature than the seam welding.  FIG. 25   b  shows how the second compartment  16  filled and sealed.  FIG. 25   c  shows how the package  11  is turned upside down, preparing it for filling the first compartment  15 .  FIG. 25   d  shows how the second compartment has been filled and sealed. It will be obvious to those skilled in the art that the package  11  is preferably manufactured as strips articulating numerous packages  11 . 
       FIG. 26  demonstrates a filling from the side. Referring to  FIG. 26   a , once again most of the contour of the package  11  is sealed prior to filling.  FIG. 26   b  demonstrates the package  11  when both compartments are filled and  FIG. 26   b  demonstrates the package  11  when both compartment are sealed. 
     Accordingly, the present invention has been described with some degree of particularity directed to the exemplary embodiments of the present invention. It should be appreciated, though, that the present invention is defined by the following claims construed in light of the prior art so that modifications or changes may be made to the exemplary embodiments of the present invention without departing from the inventive concepts contained herein.