Patent Publication Number: US-2020276388-A1

Title: Device and mixing and/or reconstitution method

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application is the national stage entry of International Patent Application No. PCT/EP2018/081375, filed on Nov. 15, 2018, and claims priority to Application No. EP 17306598.8, filed on Nov. 17, 2017, the disclosures of which are incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The disclosure refers to a device, particularly an injection device, and a mixing and/or reconstitution method. 
     BACKGROUND 
     Certain drugs are ideally administered in a liquid form, injected subcutaneously for the optimal therapeutic effect. However, some of these liquid drugs are unstable, having a shelf live that is relatively short. This can be a problem both for prophylactic treatments, where patients must inject themselves on a regular basis and therefore want to keep a reasonable supply of drug at home, and for emergency treatments, where patients need to keep a supply of the drug to hand but may not need it for weeks or longer. 
     In this case often drugs in a concentrated liquid form or lyophilized (freeze-dried) drugs are used, which usually comprise separate components, namely a powder or liquid which is much more stable and therefore has a long shelf life, and a diluent liquid. These components are typically supplied in separate vials and the user must reconstitute the drug prior to injection. Such reconstitution is often a complex process with many steps. Also, there is the risk during the reconstitution process at various points that, if the user is not careful, the drug can be contaminated. Therefore, there is a need for a system and a method which removes the possibility of user error and provides a well reconstituted and/or mixed drug in a short time. 
     From document US 2013/0296807 A1 a device for automatic reconstitution and delivering a drug to a user and a method thereof is known. There is a need for a system or injection device which reduces the possibility of user error and provides an easy and automatic operation. 
     SUMMARY 
     In certain aspects, a medical device or a method is provided. 
     In one aspect, the device comprises
         a housing,   a first chamber within the housing, wherein the first chamber contains a first material,   a second chamber comprising a first piston and a second piston, wherein the first piston and the second piston are axially moveable within the second chamber, and   a second fluid material initially contained within the second chamber between the first piston and the second piston,       

     wherein the device is adapted such that activation of the device causes movement one of the first piston and the second piston in an axial direction of the device thereby
         moving the other one of the first piston and the second piston into the same axial direction of the device,   opening a fluid communication path between the second chamber and the first chamber and   expelling the second material from the second chamber into the first chamber via the fluid communication path.       

     The present disclosure particularly refers to the mixing and/or reconstitution of a first drug component formed by or contained within the first material and a second drug component formed by or contained within the second material. Reconstitution is the rehydration of a lyophilized (freeze dried) drug (e.g. first drug component) by a diluent (e.g. second drug component). The term mixing refers to any other intermixing of any first and second drug component. 
     In some aspects, the advantage of the device may consist therein that that it provides improved and easy user operability because the user needs only to pull back the plunger until it naturally snaps back into the injection device. Then, the mixing and/or reconstitution is/are automatically effected after fluid communication between the first and the second chamber is established. After mixing and/or reconstitution a visual check of mix clarity is needed before the mixed and/or reconstituted drug comprising the first drug component and the second drug component can be injected. 
     In one embodiment the first material is a fluid or a solid material, for example, a first drug component e.g. a solid drug component, preferably a lyophilized drug, and the second fluid material is, for example, a second drug component e.g. a fluid drug component, preferably a diluent. 
     According to some aspects, the device is a cartridge, a syringe, or an autoinjector; or a combination of either one of a syringe or an autoinjector (also referred to as unit in the following) with a cartridge or a primary package attached to the distal end of the autoinjector or syringe. 
     In one embodiment a needle may be attached at a distal end of the housing. The needle is in fluid communication with the first chamber accommodated within the housing. The needle is preferably covered at its distal end by a needle boot. This prevents air from being drawn into the device, in particular as the plunger is pulled. 
     In one embodiment the first piston and the second piston close the second chamber at its proximal and distal end, respectively. 
     In a further embodiment the movement of the one piston of the first and second piston drives the other one of the first and second piston via the second material accommodated between the first piston and the second piston, i.e. the second material is the pressure transfer medium. 
     In a further embodiment the second material mixes and/or reconstitutes with the first material within the first chamber. Alternatively, the second material mixes and/or reconstitutes with the first material within the second chamber. 
     In another embodiment the other one of the first piston and the second piston comprises a needle which pierces a seal or membrane when moved into the axial direction in order to open the fluid communication path between the second chamber and the first chamber. 
     In an alternative embodiment the plunger further comprises a (e.g. cylindrical) through hole at its distal end closed by a plug (e.g. a cotter pin) which is connected with the second piston, wherein the inner surface of the plunger and/or the through hole and/or the outer surface of the plug comprises web-like elements dimensioned such that after activation of the device by pulling the plunger, e.g. in proximal direction, the second piston moves into distal direction relative to the plunger such that the web-like elements (e.g. longitudinal ribs) counteract with the plug and/or the inner surface of the through hole and/or the plunger thereby creating the fluid communication path between the second chamber and the first chamber and expelling the second drug component into the first chamber. For that the second piston and/or the through hole has a compressible outer or inner surface, respectively. The plug (cotter pin) may be formed as a stud-like element. The plug may be rigidly connected with the second piston. 
     Pulling the plunger into proximal direction causes a pressure drop within the device, e.g. in the first chamber and/or the second chamber. In one embodiment the pressure drop is first caused in the first chamber and then, after establishing fluid communication between the first chamber and the second chamber, a decrease in pressure occurs in the second chamber. In one embodiment the pressure drop in the first chamber may create a force on the second piston that forces the plug (which is connected with the second piston) to move through the through hole of the plunger. 
     In one embodiment the pressure difference inside the first chamber and the second chamber may create a force on the second piston. This force may be transferred through the second drug component contained in the second chamber and onto the first piston. The plug may thereby be moved through the through hole and, accordingly, the second piston until the first piston hits the second piston. The plug and/or the second piston may comprise a compressible outer surface which may interact with a set of web-like elements (longitudinal ribs) that may be provided at the distal end of the inner surface of the plunger forming an uneven inner surface. When the plug connected to the second piston is pushed into the uneven area (ribs) the initially formed seal may be broken. These ribs may force gaps to open up around the second piston and fluid can go through and therefore may open a fluid communication path between the second drug component contained in the second chamber and the first drug component contained in the first chamber via the through hole. The second drug component flows out the distal end of the plunger and into the first chamber of the device. In one embodiment all of the second drug component will have passed into the first chamber of the syringe before the plunger is pulled back completely. 
     Additionally, the drive mechanism is held in place by a clip feature. The clip feature may comprise a spring. A cap on the distal end of the device or the primary packaging (explained below) may sit over the clip feature, i.e. the cap covers the clip feature. When the cap is pushed downwards or pulled, e.g. into proximal direction, it may release the clip mechanism and allow the spring to apply an axial force into proximal direction to the first piston, to the second piston or the plunger. 
     In a further embodiment the device of any of the previous claims further comprises a plunger which closes a proximal end of the first chamber within the housing, wherein the plunger contains the second chamber, wherein the plunger is axially moveable within the housing of the device, wherein axial movement of the plunger within the housing, e.g. pulling into proximal direction, activates the device. In order to pull back the plunger, alternatively, a combined axial and rotational (twisting) motion may be conducted by the user. 
     In one embodiment the plunger comprises a handle at its proximal end for easy operation. 
     In other embodiments a non-return mechanism between plunger and housing prevents the plunger from moving back into the syringe until it has moved through its full proximal stroke, e.g. comprising a ratchet track provided in one axial direction (activation direction, e.g. proximal direction) and a smooth return track in the opposite axial direction. In one embodiment sudden return promotes mixing by abrupt equilibration. 
     In a further embodiment it is possible to include a needle shield in the injection device. This shield would cover the needle and retract as the user pushes the device against their skin for injection. Once the needle is removed from the skin, the shield would move back into place and thereby activate a locking mechanism so that the user is unable to retract the needle shield again. 
     In yet another embodiment the device comprises a unit and a primary packaging, 
     wherein the unit comprises the first chamber within its housing, 
     wherein the primary packaging comprises the second chamber, the first piston and the second piston, wherein the primary packaging is attachable to the distal end of the unit, 
     wherein a needle is attachable to the distal end of the unit or the second piston, 
     wherein the fluid communication path between the first chamber and the second chamber is provided either by penetration of the needle attached to the distal end of the unit through a septum seal provided within or at the second piston or by penetration of the needle attached to the second piston through a membrane covering the first chamber of the unit. 
     The primary packaging may be attached to the distal end of the unit by a luer lock or by welding, wherein in both cases detachment of the device and the primary packaging prior injection is possible. Alternatively, another releasable attachment of the primary packaging to the unit may be used. 
     In one embodiment in an initial position after attachment of the primary package to the distal end of the unit by the luer-lock the needle pierces the second piston to a certain extend but does not penetrate a septum seal within the body of the second piston. 
     In another embodiment the primary packaging comprises two parts attachable to each other, a first part comprising the second chamber with the first and second piston and the second drug component, and a second part comprising the activation mechanism. 
     The primary packaging may comprise an activation mechanism for activating the device, wherein the activation mechanism is adapted such that a user operation of the activation mechanism causes a release or operation of a driving mechanism which applies an axial force into one axial direction onto the first piston, for example, leading to a pressure increase within the second chamber and respective movement of the second piston into the same axial direction. In one embodiment the driving mechanism comprises an initially compressed spring held in place by a clip element, and user operation causes the release of the clip element. Alternatively, the driving mechanism comprises a gas spring held in place by a clip element, and user operation causes the release of the clip element. In another embodiment the driving mechanism comprises a linear electromechanical actuator. In particular, a cost effective embodiment comprises the possibility that the driving mechanism is released by means of a clip mechanism. 
     According to one aspect the activation mechanism may comprise a cap which covers the driving mechanism, wherein the cap is adapted such that by pushing in an axial direction the driving mechanism is released or operated. Alternatively, the whole primary package may be moved with respect to the unit, for example during attachment of the primary package to the unit. 
     The user convenience of the embodiment of the device comprising the primary packaging and the unit is extremely good because the user has only to press a button on the distal end of the primary packaging and wait until mixing and/or reconstitution is complete. This may be visually checked by the user. Then, the user may remove the unit from the primary packaging, may expel air by priming, if necessary, as usual and injects the drug. There is no danger of contamination during the mixing and/or reconstitution process as it all occurs within a factory-sealed environment. The mixing is very predictable and consistent and the user has only two disposable parts, namely the primary packaging and the unit. The user does not have to ensure sterility for any part as this is maintained throughout use. 
     In another embodiment the needle is attached to the distal end of the unit, wherein the second piston comprises a recess in which the distal end of the needle is located at the end of movement of the second piston. 
     According to another aspect the second material is driven into the first chamber by a high speed jet. The high speed jet has a fluid velocity of 2.5 m/s to 25 m/s, preferably a fluid velocity above 5 m/s. This high speed jet is produced in one embodiment by the second piston and/or the inner surface of the first chamber, wherein at least one of the second piston and the inner surface of the first chamber within the inlet region is structured in a way that turbulences occur in the fluid and enhance the mixing process. For example the second piston and/or the inner surface of the first chamber comprise a certain profile in order to enhance the mixing property of the high speed jet, e.g. concave cavities or one or more vanes at the front end of a plunger defining one end of the first chamber. 
     The above problem is further solved by a mixing and/or reconstitution method using a device, wherein the device comprises a housing, a first chamber within the housing, wherein the first chamber contains a first material, a second chamber comprising a first piston and a second piston, and a second fluid material initially contained within the second chamber between the first piston and the second piston, comprising the following steps after activation of the device:
         moving of one of the first piston and the second piston in an axial direction of the device,   moving of the other one of the first piston and the second piston into the same axial direction of the device,   opening a fluid communication path between the second chamber and the first chamber and   expelling the second material into the first chamber where the second material mixes and/or reconstitutes with the first material.       

     In one embodiment the other one of the first piston and the second piston comprises a needle which pierces a seal or membrane when moved into the axial direction in order to open the fluid communication path between the second chamber and the first chamber. 
     Activation is facilitated, for example, by axially moving a plunger, e.g. into proximal direction, within the housing of the device, wherein the plunger closes a proximal end of the first chamber within the housing and contains the second chamber. 
     In another embodiment the axial movement of the second piston forces a plug connected with the second piston to move through a through hole within the distal end of the plunger thereby creating the fluid communication path between the second chamber and the first chamber. 
     According to another aspect the device comprises a unit and a primary packaging, wherein the unit comprises the first chamber and the primary packaging comprises the second chamber with the first piston and the second piston, wherein prior activation the primary packaging is attached to the distal end of the unit and a needle is attached to the primary packaging or the unit for opening of the fluid communication path between the first chamber and the second chamber. 
     In one embodiment, after activation the fluid communication path between the first chamber and the second chamber is opened either by penetration of the needle attached to the distal end of the unit through a septum seal provided within or at the second piston or by penetration of the needle attached to the second piston through a membrane covering the first chamber of the unit. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       Certain embodiments will now be described in further detail with reference to the accompanying schematic drawings, wherein 
         FIG. 1  shows a concept sketch of a first embodiment of an injection device in a sectional view, 
         FIG. 2  shows the first embodiment of an injection device in a sectional view prior activation, 
         FIG. 3  shows the device of  FIG. 2  after activation, 
         FIG. 4  shows the device of  FIG. 2  during reconstitution, 
         FIG. 5  shows the device of  FIG. 2  at the beginning of injection, 
         FIG. 6  shows the device of  FIG. 2  after injection, 
         FIG. 7  shows a detail of the device of  FIG. 2  in a sectional view, 
         FIG. 8  shows a detail of the plunger of the device of  FIG. 2 , 
         FIG. 9  shows a concept sketch of another embodiment of an injection device with a primary package in a sectional view, 
         FIG. 10  shows another embodiment of an injection device with a primary package in a sectional view, 
         FIG. 11  shows the embodiment of  FIG. 10  during a first step of a mixing/reconstitution process in a sectional view, 
         FIG. 12  shows the embodiment of  FIG. 10  during a second step of a mixing/reconstitution process in a sectional view, 
         FIG. 13  shows the embodiment of  FIG. 10  during a third step of a mixing/reconstitution process in a sectional view, 
         FIG. 14  shows the embodiment of  FIG. 10  during a forth step of a mixing/reconstitution process in a sectional view, 
         FIG. 15  shows the syringe of the embodiment of  FIG. 10  prior injection in a sectional view, 
         FIG. 16  shows an injection device and a detail of a mixing unit of an embodiment of a system in a sectional view as a concept sketch, 
         FIG. 17  shows an injection device received by a mixing unit of another embodiment of a system in a perspective and sectional view prior activation of the mixing and/or reconstitution step, 
         FIG. 18  shows the system of  FIG. 17  prior to insertion of the injection device into the mixing unit in a sectional view, 
         FIG. 19  shows the system of  FIG. 17  after insertion of the injection device into the mixing unit in a sectional view, 
         FIG. 20  shows the system of  FIG. 17  after activation of the mixing and/or reconstitution step and the initial electromagnetic field produced by the electromagnetic unit in a sectional view, 
         FIG. 21  shows the system of  FIG. 17  during the mixing and/or reconstitution in a sectional view, 
         FIG. 22  shows the system of  FIG. 17  after the mixing and/or reconstitution step and during withdrawal of the injection device from the mixing unit in a sectional view, 
         FIG. 23  shows the injection device of the system of  FIG. 17  during drug administration, 
         FIG. 24  shows a slug-like element of the system of  FIG. 17  in a perspective view, 
         FIG. 25  shows a distal section of a plunger of another embodiment of an injection device in a perspective and sectional view, 
         FIG. 26  shows a first set of force profiles for different active coil sets of the electromagnetic unit of the mixing unit of  FIG. 17  in a diagram in which the electromagnetic force on the slug-like element is shown as a function of the axial position within the opening, 
         FIG. 27  shows a second set of force profiles for different active coil sets of the electromagnetic unit of the mixing unit of  FIG. 17  in a diagram in which the electromagnetic force on the slug-like element is shown as a function of the axial position within the opening, 
         FIG. 28  shows a third set of force profiles for different active coil sets of the electromagnetic unit of the mixing unit of  FIG. 17  in a diagram in which the electromagnetic force on the slug-like element is shown as a function of the axial position within the opening, 
         FIG. 29  shows an injection device and a detail of a base station of another embodiment of a system in a longitudinal section as a concept sketch, 
         FIG. 30  shows another embodiment of a system comprising an assembly with an injection device, a vial and a supporting unit as well as a base station in a perspective view from the side, wherein the base station is shown partially transparent, 
         FIG. 31  shows the disposable subassembly from  FIG. 30  in an exploded view from the side, 
         FIG. 32  shows the assembly of  FIG. 31  prior fixing at the base station in a longitudinal section, 
         FIG. 33  shows another embodiment of a system comprising an assembly with an injection device, a vial and a supporting unit as well as a base station in a perspective view from the side, wherein the base station is shown partially transparent, 
         FIG. 34  shows the disposable subassembly from  FIG. 33  in an exploded view from the side, 
         FIG. 35  shows the subassembly of  FIG. 34  in a longitudinal section prior reconstitution, 
         FIG. 36  shows the subassembly of  FIG. 34  in a longitudinal section after reconstitution, and 
         FIG. 37  shows the base station of  FIG. 33  in a perspective view from the side, partially transparent. 
     
    
    
     DETAILED DESCRIPTION 
     The first embodiment of an injection device in form of a syringe  100  depicted in  FIGS. 2 to 8  comprises a housing  101  and a needle  102  attached at its distal end. The principle of operation is demonstrated by  FIG. 1 . The needle  102  is in fluid communication with a first chamber  105  accommodated within the housing  101 , wherein the first chamber  105  contains a first drug component, for example a lyophilized drug. 
     A plunger  107  is movable within the housing  101  in an axial (longitudinal) direction with regard to the syringe  100  or housing  101 , wherein the plunger  107  closes the first chamber  105  at its proximal end. 
     Within the plunger  107  a second chamber  109  is provided containing a second drug component, for example a diluent. The second chamber  109  is closed at its distal end by a lower piston  111  and at its proximal end by an upper piston  112 . The lower piston  111  and the upper piston  112  are movable within the plunger  107 . The plunger  107  is formed as a sleeve-like element, wherein the hermetic seal of the first chamber at the proximal end of the first chamber  105  is provided by a distal end section  108  which has a bigger diameter than the remaining section of the plunger (except a handle  113 ). The diameter of the distal end section  108  corresponds to the inner diameter of the first chamber  105 . The proximal end of the plunger  107  is formed as the handle  113 . The distal end section of the plunger  107  comprises a, for example cylindrical through hole  114 . As well as admitting the passage of fluid, this through hole  114  acts as a guide for a stud-like cotter pin  117 , ensuring that piston  111  moves in a stable axial fashion. 
     The needle  102  is covered at its distal end by a needle boot  115 . The needle boot  115  is required to prevent pressure differences from allowing air into the syringe  100 . 
     In the initial position the lower piston  111  forming a seal between the first chamber  105  and the second chamber  109  while it is sitting in the area of an even inner surface of plunger  107 . To activate mixing and/or reconstitution process of the syringe  100  shown in an initial state in  FIG. 2 , in a proximal stroke, a user pulls back on the plunger  107  out of the syringe  100  into a proximal direction using the handle  113  (see in  FIG. 3  the fully pulled back position of plunger  107 ). This causes a region of low pressure to form inside the syringe  100 , in particular the first chamber  105 . The pressure further decreases as the plunger  107  is further pulled back. The plunger  107  is prevented from moving back to its original position shown in  FIG. 2  by a ratchet system between plunger  107  and housing  101  (see  FIG. 8 ). An outer projection from plunger  107  runs inside a track in housing  101 . This projection is sprung to engage with a ratchet  101   a  in the track, so that plunger  107  can only move in one direction, until it has completed the full extent of its travel: then, the protrusion is guided into a smooth return track  101   b.  The ratchet system with ratchet  101   a  ensures that the plunger  107  is pulled far enough out of the syringe  100  before it begins to move back into the syringe  100  along return track  101   b,  thereby guaranteeing that a minimum level of suction is generated (see  FIG. 3 ). The suction provided by the low pressure is needed to pull the first drug component through the through hole  114  within the plunger  107  and also to promote mixing of the first drug component and the second drug component within the first chamber  105 . 
     The pressure difference between the inside of syringe, in particular inside the first chamber  105  and the second chamber  109 , and atmosphere creates a force on the lower piston  111 . This force is transferred through the second drug component contained in the second chamber  109  and onto the upper piston  112 . They are thereby caused to move the plunger  107  down. The cotter pin  117  thereby moves through the through hole  114  and the lower piston  111  until the upper piston  112  hits the lower piston  111  (see  FIG. 3 ). The cotter pin  117  and/or the lower piston  111  comprise a compressible outer surface which interacts with a set of longitudinal ribs  120  (web-like elements) provided at the distal end of the inner surface of the plunger  107  forming an uneven inner surface (see  FIG. 7 ). When the lower piston  111  is pushed into the uneven area (ribs) the seal is broken. These ribs  120  force gaps to open up around the lower piston  111  and fluid can go through and therefore open a fluid communication path between the second drug component contained in the second chamber  109  and the first drug component contained in the first chamber  105  via the through hole  114 . The second drug component flows out the distal end of the plunger  107  and into the first chamber  105  of the syringe  100  (see  FIG. 4 , it shows the position in which the second drug component has completely emptied into the first chamber  105 ). All of the second drug component will have passed into the first chamber  105  of the syringe  100  before the plunger  107  is pulled back completely. As plunger  107  moves back further, pressure in chamber  105  drops to near vacuum. 
     Once the plunger  107  has completed its stroke in the proximal direction, the ratchet mechanism will permit it to move back into the syringe  100  until pressure has equilibrated within the syringe  100  and atmosphere. This return is sudden, and the abrupt equilibration promotes mixing between the first and the second drug component in chamber  105 . 
     At this point visual check of mix clarity is needed before the mixed and/or reconstituted drug comprising the first drug component and the second drug component can be injected. If it has not been fully mixed, the user must manually shake the device to fully mix the drug. Once the drug is fully mixed, it can be injected using the plunger  107  by moving it into distal direction by means of handle  113  as with any standard syringe (see  FIG. 6  showing the syringe  100  post injection). 
     When plunger  107  is moved to inject drug, the pressure increase within the syringe  100  causes the upper and lower pistons  111 ,  112  to move into proximal direction until a snap or clip member  112   a  at the proximal end of the upper piston  112  and snap or clip member  107   a  at the inner surface of the plunger  107  interact and mechanically lock (see  FIG. 5 , realized for example by a hook and a protrusion). This prevents any increase of pressure inside the syringe  100  from forcing the lower piston  111  and the upper piston  112  further back into the plunger  107  and therefore the second drug or the mixture of first and second drug cannot move back into the plunger  107 . In this position the lower piston  111  does not interact with the ribs  120  of the plunger anymore and hence the lower piston  11  closes the second chamber  109 . Note that depending on various detail design features, this may have already occurred during the sudden equilibration of pressure described above. 
     In an alternative embodiment, at the point where the user visually checks the clarity of the mix comprising the first and the second drug component, instead of manually shaking the syringe  100  it is allowed that the plunger  107  is continuously pulled back in order to create a region of low pressure in  105  again. This cyclical process is allowed by the ratchet mechanism forming a closed loop, which the mechanism of  107  can go around repeatably. The user may pull back the plunger and release it as many times as they like until the first and second drug components are fully mixed. 
     In a further embodiment the injection device is an autoinjector. This autoinjector may be constructed such that it includes an automated movement of the plunger in the reverse direction so that mixing of the first and second drug component is performed without user intervention. An optical check of clarity of the mix comprising the first and second drug component is still required from the user so that the autoinjector would need to be able to continue the mixing cycle for as long as the user deems necessary. This may be realized using the repeated creation of low pressure regions as outlined above. 
     The above mentioned communication between the first and the second chamber  105 ,  109  is provided by breaking of the seal provided by the lower piston  111  within housing  107 , as the lower piston  111  interacts with the ribs  120  of the plunger  107 . Alternatively, a bypass pathway may be created which allows the second drug component to flow around the piston  111 . As a further alternative there may also be used some form of needle/septum interaction as depicted in  FIG. 1 , where a needle  122  attached to the distal end of the lower piston  111  pierces a membrane  125  of the distal end section  108  of the plunger  107 . 
     The needle  102  may be changeable and removably attachable to the injection device. 
     In a further embodiment rather than the ratchet mechanism being inside the injection device  100 , it could be housed outside of the injection device within a separate housing. The housing would hold syringe  100  and plunger  107 , and guide their relative motion in the same way that the ratchet achieved. This will save space in the disposable device, as it removes a complex interaction between parts  100  and  107 . 
     In a further embodiment a combined axial and rotational (twisting) motion could be conducted by the user to pull back the plunger  107 , similar to those systems found in standard pen injectors, instead of the axial movement described above. 
     In a further embodiment it is possible to include a needle shield in the injection device. This shield would cover the needle  102  and retract as the user pushes the device against their skin for injection. Once the needle  102  is removed from the skin, the shield would move back into place and thereby activate a locking mechanism so that the user is unable to retract the needle shield again. 
     The above mentioned embodiments explained with reference to  FIGS. 1 to 8  have the advantage that they provide an improved user operability because the user needs only to pull back the plunger until it naturally snaps back into the injection device. Further, the ratchet mechanism regulates the process so that the result is independent of user skill. Further, the user may perform a visual check of clarity of the mix of the first and second drug components. The user only needs to gently shake the injection device to ensure complete mixing of any residual first or second drug component. Additionally, during the reconstitution process air is not introduced. The injection is analogue to the standard procedure which the patient knows. Further, there is no danger of contamination during the mixing and/or reconstitution process as it all occurs within a factory-sealed environment. The mixing of the first and second drug components is very predictable and consistent. Additionally, the user has only one disposable part and does not have to ensure sterility for any part as this is maintained throughout use. Although there is use of a low pressure region to promote mixing of the first and second drug components, this low pressure does not have to be held during device storage. 
     The embodiment shown in  FIGS. 10 to 15  and as a concept sketch in  FIG. 9  comprises a syringe  500  with a housing  501  and a needle  502  attached to the distal end of the syringe  500 . The needle  502  is in fluid communication with a first chamber  505  accommodated within the housing  501  of the syringe  500 . The first chamber  505  is defined at its proximal end by a plunger  507 . The first chamber  505  comprises a first drug component, for example a lyophilized drug. The needle  502  is suitable for injection of a drug into a patient. A minimal volume of air is held with the first drug component within the first chamber  505 . 
     Additionally, a primary package  510  is provided comprising a housing  510   a  (custom housing). The primary package  510  contains within a second chamber  509  formed by its housing  510   a  a second drug component, for example a diluent, accommodated between a lower piston  511  and an upper piston  512 . The lower piston  511  and the upper piston  512  are both moveable within the housing  510   a  of the primary package in an axial direction, wherein the lower piston  511  is accommodated more proximal than the upper piston  512 . The lower piston  511  contains a septum seal within its body. Additionally, it comprises at its upper or distal surface a recess or indentation  511   a.  The upper piston  512  is in contact on its distal side with a compression spring  530  as a driving mechanism which is initially compressed and held in place by a clip mechanism  536 . A cap  535  on the distal end of the primary package  510  sits over the clip mechanism  536 , i.e. the cap covers the clip mechanism  536  with the spring  530 . When the cap  525  is pushed downwards, e.g. into proximal direction, it will release the clip mechanism  536  and allow the spring  530  to apply an axial force into proximal direction to the upper piston  512 . At the proximal end of the primary package  510  attachment means, for example one part of a luer-lock  537 , is provided. As shown in  FIG. 10  prior to activation of the mixing and/or reconstruction process the primary package  510  is attached to the distal end of the syringe  500  by the attachment means, for example the luer-lock  537 . This luer-lock  537  provides a seal to ensure that the exposed parts of the needle  502  remain sterile until injection, e.g. the space around the needle  502  is sealed during device assembly and remains so until immediately prior to injection. Further, an O-ring  538  is provided which contacts the housing  510   a  of the primary package  510  and the luer-lock  537  forming an additional seal. 
     A different attachment means between the syringe  500  and the primary package  510  can be used, rather than luer-lock. Any attachment mechanism must remain secure over a shelf-life of one year and additionally be easy to engage and disengage by hand. 
     In an initial position shown in  FIG. 10  after attachment of the primary package  510  to the distal end of the syringe  500  by the luer-lock  537  the needle pierces the lower piston  511  to a certain extend but does not penetrate the septum seal within the body of the lower piston  511 . 
     In order to start with the mixing and/or reconstitution process the user presses on the cap  535  and moves it into proximal direction (see arrow  540  in  FIG. 11 ). Thereby, the clip mechanism  536  retaining the compression spring  530  is disengaged and allows the compression spring  530  to extend (see  FIGS. 11 and 12 ). The disengagement may work in one embodiment as follows. The upper piston  512  may comprise one flexible clip or more than one flexible clips (not shown) which pass through a hole in the housing  510   a,  and act against an upper face of housing  510   a.  The cap  535  comprises a recess (not shown) at its front end over the respective flexible clip. As cap  535  is pressed down, the clip enters the respective recess. Each recess is chamfered so that as the clips enter, they are compressed together, disengaging them from housing  510 a allowing the spring  530  to extend in axial direction. Both, the force from the extending spring  530  and from the user&#39;s hand can contribute to push the subsystem comprising the second drug component (the second drug component plus the upper and the lower piston  511 ,  512 ) along an axial proximal direction of the primary package  510 . Thereby the needle  502  is forced to penetrate the septum seal of the lower piston  511  thereby forming a fluid communication between the second chamber  509  and the first chamber  505  of the syringe  500 . The lower piston  511  is stopped from moving further by an end-stop feature within the primary package  510 , for example a projection  513  at the inner surface of the housing  510   a  (see  FIG. 10 ). In this position the distal end of the needle  502  is located within the recess  511   a  of the lower piston  511 . The upper piston  512  is further forced to move into proximal direction and into the direction of the lower piston  511  thereby increasing the pressure within the second chamber  509  and pushing the second drug component through the needle  502  into the first chamber  505  (see arrow  541  in  FIG. 12 ). 
     The recess  511   a  at the lower piston  511  allows the needle  502  to protrude through the lower piston without ever touching the upper piston  512  (see  FIGS. 11 and 13 ). It is noted that the lower piston  511  and the upper piston  512  eventually met when whole content of the second drug component is transferred from the second chamber  509  into the first chamber  505 . The recess  511   a  has the advantage that if the upper piston  512  contacts the lower piston  511  the needle  502  would not contact the upper piston  512  and consequently the flow of the second drug component through the needle  502  would not stop. In another embodiment the recess may be located in upper piston  512  rather than in lower piston  511 , for the same effect. 
     When the second drug component enters the first chamber  505  it will be under substantial pressure which creates a high speed jet (for example with a fluid velocity of 2.5 m/s and faster, preferably with a velocity of 5 m/s and faster) in the case that the second drug component is fluid. This jet dislodges the first drug component and causes turbulent mixing. All of the second drug component will be mixed into the first drug component by the time the upper piston  512  finishes expelling of the second drug component into the first chamber  505 . The spring  530  generates all of this pressure to drive the second drug component and ensures reliable and repeatable mixing independent of user strength or skill. The user may visually check that the first and second drug components are fully mixed. 
     Then the user may unscrew (see arrow  542  in  FIG. 14 ) or otherwise detach the primary package  510  from the syringe  500 . The syringe is now ready to inject (see  FIG. 15 ) the mixed and/or reconstituted drug contained within the first chamber  505 . 
     In another embodiment rather than using a standard syringe  500  for the accommodation of the first drug component, a cartridge could be used to be placed in another device for injection. 
     In one embodiment the plunger  507  within the syringe  500  may be custom shaped to improve the mixing resulting from the fluid jet. For example, the plunger  507  may comprise one or more concave cavities at its front end defining the first chamber  505 . Within such cavity the jet of fluid is deflected out to better penetrate the corners of first chamber  505 . Alternatively or additionally, one or more vanes at the front end of plunger  507  defining the first chamber  505  may achieve a similar effect. 
     In another embodiment the proximal end of the needle  502  within the syringe  500  may be shaped so that a jet of fluid is directed towards the proximal direction, keeping the majority of turbulent mixing close to the first drug component. For example, the proximal end of needle  502  may have a bend so that the jet enters first chamber  505  at an oblique angle, setting up swirl flows to promote mixing. Alternatively or additionally, through holes within the side wall of the proximal end of the needle  502  may be provided in order to create multiple jets. 
     In a further embodiment the primary package  510  may be housed inside an autoinjector so that manual injection is not necessary. The autoinjector would have to allow removal or separation of the primary package  510  prior to insertion. 
     In another embodiment the attachment of the syringe  500  and the primary package  510  may be more permanent. For example the syringe  500  and the primary package  510  may be welded together, with the weld creating a hermetic seal that replaces the function of the seal  538  and the luer-lock connector  537 . In this case, a mechanism must allow the syringe  500  and the primary package  510  to separate before injection. This may be realized by a snap mechanism, wherein the housing  501  of the syringe  500  and the housing  510   a  of the primary package  510  may simply snap apart under user pressure. 
     In a further embodiment, the primary package  510  may comprise two separate parts, one holds the spring and the other one holds just the second chamber with the second drug component and the upper and lower piston  511 ,  512 . This would remove the need to weld the primary package  510  together during manufacture. The parts would have to interlock prior attachment to the syringe  500 . 
     In further alternative embodiments, the force for driving the upper piston  512  may be generated not by a compressed spring  530  as explained above but instead by another driving mechanism, for example by a gas spring or by a linear electromechanical actuator. 
     In another embodiment the sizes of the first chamber  505  and the second chamber  509  as well as the needle gauge can be customized in order to create a suitable jet profile for effective mixing of the particular first and second drug components. 
     The needle  502  could, instead of being staked into the syringe  500 , be changeable. In this case one needle may be used for mixing and/or reconstitution but the user swaps it for a separate, sterile needle for injection. 
     In a further embodiment the mixing and/or reconstitution process may be activated by movement of the primary package, for example its housing, rather than a pushing onto the cap  535 . For example, when the user attaches the primary package  510  to the syringe  500  the lower and upper pistons  511  are automatically driven such that the needle  502  fully penetrates the septum, starting the flow of the second drug component into the first chamber  505 . 
     The advantage of the embodiment explained above with regard to  FIGS. 9 to 15  consists therein that the user convenience is extremely good because the user has only to press a button on the distal end of the device and wait until mixing and/or reconstitution is complete. This may be visually checked by the user. Then, the user may unscrew the syringe  500  from the primary package  510 , expels air by priming as usual and injects the drug. There is no danger of contamination during the mixing and/or reconstitution process as it all occurs within a factory-sealed environment. The mixing is very predictable and consistent and the user has only two disposable parts, namely the primary package  510  and the syringe  500 . The user does not have to ensure sterility for any part as this is maintained throughout use. 
     The embodiment described in  FIGS. 17 to 28  comprises an injection device in form of a syringe  200  and a mixing unit in form of a base station  250 . The syringe  200  comprises a housing  201  with a first chamber  205  and a plunger  207  which closes the first chamber  205  at its proximal end. At its distal end the plunger  207  forms a second chamber  209  within a respective inner space of the plunger  207 . The first chamber  205  contains a first drug component, for example a diluent, wherein the second chamber  209  contains a second drug component, for example a lyophilized drug. Additionally, a moveable slug-like element  210  with a magnetic or paramagnetic characteristic is provided within the second chamber  209 . The distal end of the second chamber  209  of the plunger  207  is covered by a seal  211 . The seal may be realized by a foil or membrane, for example comprising or consisting of an aluminium-polymer laminate or a low-permeability polymer such as a cyclic olefin. At the distal end of the housing  201  of the syringe  200  a needle  202  with a needle cover  215  is attached. The needle  202  is in fluid communication with the first chamber  205  of the syringe  200 . The needle cover  215  protects the needle  202 , avoids its contamination and prevents the user from needle sticks. 
     The slug-like element  210  may comprise or is composed of, for example, at least one of the following materials comprising sintered Neodymium-Iron-Boron (NdFeB), preferably with a medical-grade coating, Samarium-Cobalt (SmCo) and Aluminium-Nickel-Cobalt (AlNiCo). The middle or main section of the element  210  is preferably formed as a cylinder. Alternatively, it may have a shape of a barrel or of a section of a sphere. One distal end  210   a  of this element  210 , which is shown in  FIG. 24  in detail, may be shaped as a sharp tip to puncture the seal  211 . Additionally, the proximal end  210   b  of the element  210  may be tapered in order to help the element  210  to slide back up into the plunger  207 , so that it does not get trapped between the plunger  207  and the inner wall of the syringe housing  201 , thereby preventing full injection of the mixed and/or reconstituted drug. 
     The seal  211  may be provided such that it bursts in a way that does not create loose parts. Equally, the proximal end of the needle  202  may be made too small for foil parts to enter, or a filter may be added inside the syringe (e.g. at the distal end of the first chamber, within the first chamber  205 ) preventing that foil parts enter the needle  202 . 
     The base station  250  comprises a series of electromagnetic coils  260   a  plus milled steel pole pieces  260   b  accommodated in between two adjacent electromagnetic coils  260   a  to guide the magnetic flux and improve efficiency. The electromagnetic coils  260   a  and steel pole pieces  260   b  together form the electromagnetic unit  260 . The electromagnetic unit  260  encases a cylindrical opening  265  which is provided to receive the distal end of the syringe  200 . An inserted syringe  200  within the opening  265  is shown for example in  FIGS. 17, 19, 20, and 21 . The base station  250  further comprises a control unit  270  and a power supply with batteries  273  in order to provide electrical energy for the components of the base station  250 . Further, a button  275  is provided by pressing of which the mixing and/or reconstitution of the first and second drug component may be activated by the user when the syringe  200  is inserted in the opening  265 . The opening of the base station  250  may contain a sensor for the syringe  200  recognizing the correct and full insertion of the syringe  200  within the opening  265 . In case the sensor does not notice a syringe  200  correctly inserted within the opening  265  an activation of the button  275  shall not start the mixing and/or reconstitution step. 
     In the first step, the syringe  200  is inserted into the opening  265  of the base station  250  (see  FIG. 18 ) so far that its body  201  is fully received by the opening  265  (see arrow  213 ). By pushing the button  275  the user activates the electromagnetic unit  260  energizing the coils  260   a  so that a large force into an axial direction of the syringe  200 , for example a distal direction, is exerted on the slug-like element  210  during a pre-determined time period, causing it to puncture the seal  211 . Thereby it is allowed to the first and second drug component to mix within the first chamber  205 , for example to reconstitute both components. 
     In one embodiment the base station  250  comprises a separate interlock system holding the syringe  200  within the opening  265  of the base station  250  until mixing is complete. 
     Once the element  210  has punctured the seal  211  it is free to move along the entire length of the first chamber  205  into an axial direction of the syringe  200  back and forth (see arrow  214 ).  FIG. 20  shows lines of magnetic flux with flux density, for the initial stage, in which the slug-like element  210  is accelerated in order to pierce the seal  211 . The lines of the magnetic field are marked with the reference number  262 . Afterwards, the coils  260   a  and the magnetic element  210  form a brushless linear motor, i.e. a Lorentz force device, whereby energizing different coils in different directions and at different times causes the element  210  to move backwards and forwards in the axial (longitudinal) direction (arrow  214 ) of the syringe  200  within a pre-determined time period to effect mixing within the first chamber  205  (see  FIG. 21 ). In one embodiment the base station  250  comprises four coils  260   a  accommodated side by side along the axial direction (see arrow  214 ), wherein at any one time, two coils  260   a  are active (see  FIG. 20 ) alternating with the other two coils  260   a.  The two active coils  260   a  are energized in opposite directions, and interact with the two magnetic poles of the element  210  to generate an axial force such that, in one step, one coil  260   a  repels one magnetic pole of the element  210  and the other coil  260  of the two active coils attracts the other magnetic pole of the element  210 . Only energizing coils  260   a  close to element  210  improves the efficiency of the system. By setting precise levels of power in each coil  260   a,  the speed and position of the element may be accurately controlled. If each coil  260   a  has a resistance of 40 Ohms, the drive system may include a boost power supply, e.g. providing 200 V, driving the coils  260   a  via a half bridge for 0.1 seconds. This could generate 1 kW in the coils, which would generate the large forces needed to initially puncture the foil seal. The control unit  270  of the base station  200  provides a predefined number of cycles of energizing different coils of the electromagnetic unit  260  that guarantees a homogenous reconstituted or mixed drug. At the end of the process (see  FIG. 22 ), the element  210  rests in a position within the previous second chamber  209  of the plunger  207  whereby it does not hinder injection. As shown in  FIG. 24 , the element  210  has a tapered proximal end  210   b  to help it re-enter the plunger  207 . By means of the control unit  270  which is connected with the electromagnetic unit  260  a smooth slide of the element  210  into the plunger  207  is provided during injection. 
     Finally, as shown in  FIG. 22 , the syringe  200  is removed from the base station  250 . In order to inject the mixed and/or reconstituted drug containing the first and the second drug component the user removes the needle cover  215 , expels any air from the syringe by means of priming and finally injects the drug mixture (see  FIG. 23 ). 
     The  FIGS. 26 and 27  show the forces generated at 10 W and 900 W for five different coils of the electromagnetic unit  260 , respectively, for the geometry shown in  FIG. 17 . At 10 W, forces are ample to dislodge the second drug component and mix the first and second drug component reliably. At 900 W, forces are adequate that the element  210  is accelerated and punctures the seal  211 , subject to the geometry of the slug-like element  210 . This high power is only needed for a very brief period of time, namely the time in which the seal  211  is punctured, so total energy used is low and the coils of the electromagnetic unit  260  do not overheat. 
     In another embodiment an additional plate-like metal element  220 , made from a soft magnetic material for example comprising steel, could be used to hold the paramagnetic or magnetic element  210  in place until the syringe  200  is placed in the base station  250  and activated, and also to keep the element  210  inside the plunger during injection. The plate-like element  220  is accommodated within the plunger  207  close to the proximal end of the second chamber  209  (see  FIG. 25 ). The plate-like element  220  is as close as possible to element  210 , by making the wall between it and chamber  209  as thin as practical, preferably the thickness may be less than 1 mm. This means that element  220  can be small and still provide sufficient attraction to element  210 . For example, element  220  may have a thickness of more than 0.5 mm, preferably more than 1 mm. The plate-like element  220  prevents that no amount of inadvertent agitation during (e.g.) shipping or dropping the device prior to use will cause the seal  211  to rupture. In an alternative embodiment the element  220  could be a separate element which the user has to remove or an element that is dislodged on insertion of the syringe  200  in the base station  250 . For example, the element may be a steel collar piece accommodated around the outside of housing  201  of the syringe  200 , which is slid away on insertion into base station  250 . Anyhow, the element  220  generates a small enough force that the coils of the electromagnetic unit  260  can easily overcome it. 
     If the slug-like element  210  is a permanent magnet, it is preferred to use a medical-grade coating to prevent contact between the magnetic material and the first or second drug component. 
     Instead of using a moving magnetic material for the electromagnetic element  210  (a “Lorentz force” device or linear brushless motor), the element  210  could made of a soft magnetic material, e.g. mild steel. In this case only one coil is needed to be activated at any time and the syringe works as a simple electromagnetic, e.g. a solenoid actuator.  FIG. 28  shows that such an actuator generates even higher instantaneous forces for a given power input but these forces vary more with the position of the soft magnetic element within the first chamber  205  so that the coils must be carefully sized/placed to avoid positions of the element  210  in which no force is generated. If the element  210  is a soft magnetic material, it could be, for example, medical-grade stainless steel, in which case no coating is required. In that case, the magnetic element  210  may form sharp edges to more effectively puncture the foil. 
     In another embodiment instead of using a simple syringe, the injection device can be complete autoinjector. The above explained process may be conducted as indicated above: the autoinjector containing the first and second chambers comprising the first and second drug component is inserted into the base station, the components are mixed and the autoinjector is removed ready to use. 
     As a further embodiment, e.g. for high-value drugs, it may be economically viable to include the electromagnetic unit, the power supply and the control unit into a disposable component of the injection device so that no separate base station is needed. 
     In a further embodiment the internal shape of the needle  202 , of the first chamber  205  and of the housing  201  of the syringe  200  may be designed such that the element  210  will not hinder injection should the element  210  remain in the first chamber  205  after mixing. 
     Rather than a syringe or an autoinjector, the injection device may be a cartridge suitable for use with a separate injection device. In other words, it is a syringe, but missing the long plunger that enables a user to carry out injection, and also missing the needle: the injection device includes the system for penetrating the skin, and also the system for driving injection. 
     The system shown in  FIGS. 16 to 28  comprising a syringe  200  and a base station  250  for drug reconstitution and/or mixing is extremely good operationally because there is no danger of contamination during the reconstitution process as it all occurs within a factory-sealed environment. The disposable part comprising the syringe  200  is very compact. The mixing/reconstitution is very predictable and consistent with a low amount of steps. There is only one disposable part per injection. The design of this base station offers maximum flexibility across injection device types namely pre-filled syringes, autoinjectors and cartridges. The injection device does not need a needle fitted in advance of reconstitution. 
     The embodiment of a drug reconstitution system shown in  FIGS. 29 to 32  comprises a prefilled injection device in form of a syringe  300  with a housing  301  and a vial  308 . The syringe  300  comprises a first chamber  305  which contains a first fluid drug component, for example a diluent. The vial  308  comprises a second chamber  309  containing a second solid and/or fluid drug component, for example a lyophilized drug. Additionally, the system comprises a supporting unit  310  which consists of, for example, two parts  310   a  and  310   b  (see  FIG. 31 ) which may be releasable connected to each other, e.g., by means of a snap connection. The syringe  300  is further connected to a needle  302 , wherein the needle  302  is covered by a needle boot  315 . The syringe  300  further comprises a plunger  307  at its proximal end opposite from the distal end of the syringe  300  which is connected to the needle  302 . The plunger  307  is movable within the housing  301  of the syringe  300  along an axial (longitudinal) direction of the syringe  300 . The plunger  307  closes the proximal end of the first chamber  305 . If the plunger  307  is moved in proximal direction an underpressure is generated within the first chamber  305 . If the plunger  307  is moved in distal direction the first drug component is expelled from the first chamber  305  through the needle  302 . 
     The drug reconstitution system further comprises a base station  350  comprising a housing  351  and, within the housing  351 , at least one drive unit  370 . 
     The supporting unit  310  is formed like a capsule or a hollow cylinder which comprises two sections with different diameter when both parts  310   a,    310   b  shown in  FIG. 31  are connected to each other (see  FIG. 30 ). Alternatively, the connection of both parts  310   a,    310   b  of the supporting unit  310  may be a hinge connection. The supporting unit  310  forms a first recess  311  and the second recess  312  on the inner side of each part  310   a,    310   b  such that the supporting unit  310  locks the pre-filled syringe  300  and the vial  308  in a locked position during transit and storage, preventing them from making contact with each other. Therefore, the syringe  300  is fixed such in the first recess  311  and the vial  308  is fixed such in the second recess  312  that they have a predetermined distance from each other (see  FIG. 32 ). For example the first recess  311  and the second recess  312  each may comprise at least one web or similar projection at its inner surface which forms a snap connection with the housing  301  of the syringe and/or the needle boot  315  or which forms a snap connection with the vial  308 , for example at its neck section (see  FIG. 32 ). If the syringe  300  and the vial  308  are fixed within the supporting unit  310  and both parts  310   a  and  310   b  of the supporting unit  310  are connected to each other, a self-supporting assembly is formed which locks the pre-filled syringe  300  and the vial  308  in position, for example, during transit and storage, preventing them from making contact with each other. 
     The vial  308  comprises a seal  313  which covers the vial  308  at its front end of the neck. The seal  313  closes the second chamber  309  hermetically. 
     The drive unit  370  of the base station  350  comprises for example a first motor and a second motor. Additionally, an optional high frequency transducer  371  as a vibrating unit and further an optional heater element  372  are provided within the housing  351  of the base station  350 . The base station  350  further comprises a recess  365  at the upper side of the housing  351  which is adapted to receive and releasably fix the assembly comprising the syringe  300 , and the vial  308  when locked within the supporting unit  310 . Therefore the recess  365  at least partly corresponds to the outer circumference of the assembly. 
     In order to reconstitute a drug and to prepare the syringe  300  for injection the assembly shown in  FIG. 32  comprising the syringe  310 , the supporting unit  310  and the vial  308  is inserted into the recess  365  of the base station  350  by the user and fixed there. The syringe  300  with the needle  302  and the vial  308  is now in the initial position. The base station  350  has the following interfaces to the assembly shown in  FIG. 32 :
         the vial,  308 , is held stationary;   the syringe  300  engages, for example with its housing  301 , with a first linear slide  374  that is actuated in an axial direction by a motor drive unit  370 ;   and plunger  307  engages with a second linear slide  375  that is actuated in an axial direction by a second, independent, motor drive unit (not shown).       

     The fixing of the assembly of  FIG. 32  may be achieved either through:
         passive clips, which the user can overcome to pull the assembly out; or,   a separate motor drive unit can operate a clamping mechanism to hold the assembly in place during the reconstitution process; or,   the assembly shown in  FIG. 32  can only engage/disengage with the first and second linear slides when they are in their initial positions.       

     In operation, in the position in which the assembly of  FIG. 32  is inserted, that assembly may have to pass through slots in housing  351  that align with the first and second linear slides. Once the drive units have begun to move, features on the assembly no longer align with the slots in housing  351 , and the user cannot remove the assembly prematurely. Thereby, the assembly is held at an angle in the base station  350  with the vial  308  positioned higher than the syringe  300  so that second component from the second chamber  309  of the vial  308  rather than air is drawn into the syringe  300  during preparation. This is realized by the tilting angle of the recess  365  of the base station  300  with regard to the opposite platform face  366  on which the base station  350  stands. The base station  350  contains a feature to unlock the parts of the supporting unit  310  allowing the syringe housing  301  and the vial  308  to move relative to each other when positioned within the recess  365  of the base station  350 . For example, this unlock feature may consist of a flexible hook element inside supporting unit  310  which locks into a feature on the syringe housing  301 , so that the two parts cannot move relative to each other. A pin feature in recess  365  may penetrate a small hole in supporting unit  310 , to push the flexible hook element out of the way, enabling housing  301  to move relative to supporting unit  310 . Alternatively, rather than being a fixed pin, this unlock feature could be actively driven, e.g. with a solenoid. The feature should remain unlocked as the assembly is removed from the base station  350 , so that the user can withdraw the syringe  300  for injection. 
     In the next step the first motor of the drive unit  370  drives the housing  301  of the syringe  300  towards the vial  308  by means of the first slide  374 . The needle boot  315  is compressed against the vial  308  and the needle  302  is inserted into the seal  313  of the vial  308  forming a fluid connection with the second chamber  309  of the vial  308 . The syringe  300  with the needle  302  is moved toward the vial  308  and inserted into the second chamber  309  for a pre-defined distance. At the same time the second motor of the drive unit  370  moves the syringe plunger  307  by means of the second slide  375  towards the vial  308  at the same rate so that the volume inside the first chamber  305  stays unchanged during this step. The vial  308  and the syringe  300  with the needle  302  are now in an activated position. 
     In the next step, after the activated position of vial  308  and syringe  300  is reached, with the first motor held stationary, the second motor drives the syringe plunger  307  towards the vial  308  by means of the second slide  375 , expelling the first drug component, for example the diluent, into the second chamber  309  of the vial  308  forming a mixture of the first drug component and the second drug component within the second chamber  309 . 
     A range of mechanisms can be used to convert the rotational motion of the drive units  370  into a linear action on housing  301  of syringe  300  and plunger  307 . The unit shown in  FIG. 30  comprises a lead screw, where the motor of drive unit  370  turns a threaded bar. There is a nut running on the threaded bar, which is fixed both rotationally and axially to the first linear slide  374  that engages with housing  301  of syringe  300 . As the threaded bar is rotated, the nut is driven along the threaded bar, driving housing  301  in an axial direction. The same may be provided by the second linear slide  375  coupled to plunger  307 . Alternatively, the threaded bar can be fixed rotationally and axially to the profiled component engaging with  301  or  307 , and the nut is driven rotationally by the motor. This nut can form part of the motor itself. 
     Once all first fluid drug component has been transferred into the second chamber  309 , the transducer  371  may agitate the vial  308  containing the mixture of the first drug component and the second drug component, promoting mixing of, for example, the drug powder and the diluent. This transducer  371  may be a piezoelectric transducer, i.e. a piece of piezoelectric ceramic between two electrodes. If an oscillating voltage is applied to the electrodes, the thickness of the transducer oscillates, creating a pressure wave. Due to the inherently small displacements of piezoelectric transducers, very good acoustic coupling is necessary between the transducer  371  and the vial  308 . This is likely to require at least a spring-loaded contact between the transducer and the vial, or even a liquid- or gel-based coupling. Alternatively, the transducer  371  may be an electromagnetic linear actuator, such as a voice coil or a solenoid. This operates at lower frequency, but the larger displacements achievable mean that it is simpler to transmit the agitation into the mixture. Alternatively, a motor driving an imbalanced load (a vibration motor) could be used to generate the oscillating pressure waves. At the same time or afterwards, the heater element  372  may heat up the mixture to a pre-set temperature, for example in the range of 18° C. to 26° C., reducing the likelihood that a cold mixture causes discomfort during drug injection into the patient. The heater element  372  may be a simple resistive element, generating heat when an electric current passes through. A thermistor (temperature measurement sensor) would be necessary to ensure that it is not overheated, unless the system is designed so that it is physically impossible for any fault to lead to overheating. Alternatively, heat can be supplied through a solid-state heat pump, i.e. a Peltier device. 
     Once the second drug component is fully dissolved in the first drug component or the other way around forming a reconstitution or once both components are mixed and—if applicable—the reconstitution or mixture reaches the correct temperature, the second motor drives the syringe plunger  307  by means of the second slide  375  into axial direction away from the vial  308  drawing the mixture or reconstitution into the syringe  300 , namely from the second chamber  309  of the vial  308  into the first chamber  305  of the syringe  300 . Since the vial  308  is positioned higher than the syringe  300 , and the needle  302  is at the lowest point of the vial  308 , the base station ensures that only the mixture or reconstitution of the second chamber  309  has drawn into the syringe  300 , minimizing the air volume in the syringe  300 . In the next step the first motor and the second motor of the drive unit  370  act together to pull the syringe  300  and with it the needle  302  out from the vial  308 . The user then takes the syringe  300  out from the recess  365  of the base station  350 , removes the supporting unit  310  from the syringe and manually injects the reconstituted or mixed drug contained in the first chamber  305  of the syringe  300 . The vial  308  is a disposable device, wherein the syringe  300  may be a disposable or reusable device. 
     The embodiment of a drug mixing or reconstitution system shown in  FIGS. 33 to 37  is similar to the embodiment shown in  FIGS. 29 to 32  but with an autoinjector  400  instead of the syringe  300 . An element of this embodiment of the system having the same last two digits of the reference number but a leading digit 4 instead of 3 corresponds to the respective element of the system shown in  FIGS. 29 to 32 . 
     The autoinjector  400  may be a traditional spring driven design or one that is actuated by a fluid, for example, air pressure. In the following, certain aspects are explained by means of an autoinjector  400  actuated by air pressure which is provided to users with atmospheric pressure in an air chamber  414  initially. Certain aspects of the invention work similarly with an autoinjector using a spring as the drug delivery energy source. 
     The drug reconstitution system comprises the autoinjector  400 , a vial  408  and a supporting unit  410  which comprises two parts  410   a  and  410   b  for connecting to each other and fixing the autoinjector  400  and the vial  408  within forming an assembly for transit and storage in a pre-defined distance or relative position to each other. Additionally, a base station  450  is provided. 
     The autoinjector  400  further comprises a first chamber  405  and a needle  402 . The first chamber  405  contains a first drug component, for example a diluent. The vial  408  comprises a second chamber  409  containing a second drug component, for example a lyophilized drug, and a seal  413  covering the vial and closing its second chamber  409  hermetically. The system comprises further a needle boot  415 . 
     For reconstitution or mixing of the first and second drug components of the autoinjector  400  and the vial  408  the needle boot  415  is attached to a first recess  411  of the supporting unit  410  as shown in  FIG. 36 . Then, the assembly is composed by connecting the first and second part  410   a,    410   b  of the supporting unit  410  to each other and inserting the vial  408  and the autoinjector  400  into their respective first and second recess  411 ,  412 . For attachment of the autoinjector  400  to the supporting unit  410  a needle guard  417  of the autoinjector  400  has to be retracted in order to expose the needle  402  which is then covered by the needle boot  415  (see  FIG. 35 ). The autoinjector  400  and the vial  408  are fixed to the supporting unit  410  for example by a snap connection. 
     In order to reconstitute a drug with the system shown in  FIGS. 33 to 37  the assembly (see  FIG. 35 ) is inserted into a recess  465  of the base station  450  as shown in  FIG. 33 . Now the autoinjector  400  and the vial  408  are in an initial position. A feature on the base station  450  unlocks the parts  410   a,    410   b  of the supporting unit  410 , allowing the autoinjector  400  with the needle boot  415  and the vial  408  to move towards each other along an axial direction of the autoinjector  400  by means of a first slide connected to the drive unit  470 . For example, the unlock feature may consist of a flexible hook element projecting from the inner surface of the supporting unit  410  which locks into a respective recess on outer surface of the autoinjector housing  401 , so that the supporting unit  410  and the autoinjector housing  401  cannot move relative to each other. A pin feature in recess  465  may penetrate a small through hole in supporting unit  410  when correctly attached to the base station  450  within the recess  465 , to push the flexible hook element out of the way, enabling autoinjector housing  401  to move relative to the supporting unit  410 . Alternatively, rather than being a fixed pin, this unlock feature could be actively driven, e.g. with a solenoid, or a second drive motor. Alternatively, instead of activating a release mechanism inside supporting unit  410 , the unlock feature could fully open supporting unit  410  up, i.e. separate the two parts  410   a,    410   b  of the autoinjector housing. The unlock feature should remain unlocked as the assembly is removed from the base station  450 , so that the user can withdraw the syringe  400  for injection. 
     In the next step, a needle of the base station  450  pierces a septum  418  at the autoinjector body  401 , allowing an air pump  473  of the base station  450  to pump air in and out an autoinjector air chamber  414  comprising the plunger  407 . The needle is fluidly connected to the air pump  473 . Then, a first motor of a drive unit  470  of the base station  450  pushes the autoinjector  400  towards the vial  408 . Thereby the needle guard  417  retracts further into the autoinjector body  401  and the needle boot  415  is compressed so that the needle  402  is inserted into the vial  408 , e.g. its second chamber  409 , through the seal  413  for example formed as a rubber cap. The first slide connected with the drive unit  470  engages with a feature on housing  401 , and drives it axially. A range of mechanisms can be used to convert the rotational motion of the drive unit motor into a linear action on the autoinjector body  401 . The mechanism shown in  FIG. 37  is a lead screw, where the motor turns a threaded bar. There is a nut running on the threaded bar, which is fixed both rotationally and axially to a first linear slide (e.g. a profiled component) that engages with the autoinjector body  401 . As the threaded bar is rotated, the slide is driven along the threaded bar, driving autoinjector body  401  in an axial direction towards the vial  408  thereby inserting the needle  402  into the second chamber  409 . The autoinjector  400  and the vial  408  are now in an activated position. 
     Afterwards, a second motor of the drive unit  470  of the base station  450  activates a mechanism of the autoinjector  400  to unlock a plunger  407  of the autoinjector  400  allowing the plunger  407  to move using a plunger locking mechanism  420 . The locking mechanism  420  exists so that once the autoinjector  400  is filled and primed, it does not release its stored energy and inject drug until it is activated by the user. It is shown in  FIG. 35  as a simple locking pin, but it can be any catch feature that locks the plunger in position. This catch is later released to initiate drug delivery, e.g. the user presses a button to move the catch away from the plunger, or the catch is released when the needle guard is pressed against the skin. However, it must also be operated by the base station  450 , in order that the base station  450  can perform mixing and priming of the autoinjector  400 . Therefore, second motor of the drive unit  470  releases the autoinjector plunger  407 , for example by releasing the catch of the locking mechanism  420 . Then, driven by the drive unit  470 , the air pump  473  of the base station  450  pumps air into the air chamber  414  surrounding the plunger  407  via the needle which pierces the septum  418  thereby pushing the plunger  407  towards the vial  408  to expel the first drug component from the first chamber  405  at the same time. Accordingly, the first drug component of the first chamber  405  can now be mixed and/or reconstituted within the second chamber  409  of the vial  408  with the second drug component. 
     For mixing and/or reconstituting, the base station  450  may vibrate the vial  408  at a high frequency using a transducer  471  (vibrating unit) and/or warm up the mixture within the vial  408  at the same time using a heater element  472 . Once the mixture or reconstitution is prepared, the air pump  473  of the base station  450  works in reverse to pump air out of the air chamber  414  generating a vacuum in order to pull the plunger  407  away from the vial  408  such that the drug mixture or reconstitution is drawn into the first chamber  405  of the autoinjector  400 . In the next step the second motor of the drive unit  470  activates the plunger locking mechanism  420  to lock the plunger  407  in position again. Now, the air pump  473  pumps compressed air into the air chamber  414 , this time as the drug delivery power source. Then the first motor draws the autoinjector  400  out of the vial  408 , allowing the user to remove the assembly  410  from the base station  450 . 
     In order to use the autoinjector  400 , the user pulls to remove the vial  408  and the supporting unit  410  by opening the two parts  410   a,    410   b.  This also removes the needle boot  415  from the autoinjector  400  in the same step. Removal of the needle boot  415  has the additional advantage that it removes the chance of injecting rubber debris from the needle boot  415  into the patient. This step also reveals the needle guard  417  (see  FIG. 36 ). Then, the user presses the needle guard  417  onto the injection site, pushing the needle guard  417  into the autoinjector body  401  and inserting the needle  402  into the patient. A feature of the needle guard  417  activates the mechanism of the autoinjector  400  to unlock the plunger  407 . In one embodiment of the unlock mechanism there is an axial extension of needle guard  417  towards the locking mechanism  420 . As the needle guard  417  is pushed back into housing  401 , this extension engages with a ramp or similar mating feature in locking mechanism  420 , moving it out of the plunger  407  or otherwise disengaging the locking mechanism. The plunger  407  then moves towards the needle  402  under air pressure thereby providing injection of the mixture or reconstitution into the patient. Once the injection is finished, the user removes the autoinjector  400  from the injection site and the needle guard  417  extends outwards under a spring force of a spring  419  to cover the needle  402  again. The needle guard  417  also locks itself against the autoinjector body  401  to prevent needle  402  stick injuries. 
     In an alternative embodiment of the above explained autoinjector concept actuated by air pressure an autoinjector concept using a spring as the drug delivery energy source can be used. The method is basically the same except for during the mixing and/or reconstitution stage the second motor of the drive unit  470  actuates the plunger  407  to expel the first drug component into the second chamber  409  of the vial  408 . After mixing or reconstitution, the second motor withdraws the plunger  407 , producing an underpressure within the first chamber  405  and drawing the mixed or reconstituted drug into the autoinjector  400 , namely its first chamber  405 . Completion of this movement happens when the plunger  407  reaches its locking position at the proximal end, wherein this action may compress a delivery spring ready for drug delivery at the same time. Activation happens analogously to the above embodiment, when the user presses the needle guard  417  onto the injection site, pushing the needle guard  417  into the autoinjector body  401 , inserting the needle  402  into the patient and unlocking the plunger  407 , allowing the spring to drive the plunger  407  downwards to expel the drug from the first chamber  405 . Although the above example states compressing the delivery spring when drawing the drug back into the autoinjector  400  it is also possible for the spring to be compressed during manufacturing. 
     In a further alternative embodiment the mixture comprising the first drug component and the second drug component can be transferred back and forth between the first chamber  305 ,  405  of the autoinjector or syringe and the second chamber  309 ,  409  of the vial  308 ,  408 . Thereby, the respective needle  302 ,  402  preferably creates water jet during transfer, promoting mixing or reconstitution. 
     Before the user injects the mixed or reconstituted drug the user may prime the syringe  300  manually. In another embodiment instead of priming the syringe  300  manually, the base station can be provided with a respective feature to prime the syringe  300 . This can be done, for example, by using the second drive mechanism which axially moves the plunger  307  a small distance, whilst holding housing  301  still, so that any air in the syringe is expelled. The same applies to the autoinjector  400 , wherein the autoinjector may either be powered by air pressure or a conventional mechanical spring. 
     The main advantage of the above described drug reconstitution system with a base station  350 ,  450 , a syringe  300  or autoinjector  400 , a supporting unit  310 ,  410  and a vial  308 ,  408  consists therein, that it automates the reconstitution operation, thereby removing all manual steps. If a transducer  371 ,  471  is provided in the base station  350 ,  450  it improves the consistency and repeatability of reconstitution. The system further reduces the number of devices presented to the user and removes the need to disinfect the drug vial  308 ,  408 . Additionally, it reduces the chance of injecting air into the patient. With regard to the autoinjector version, wherein the base station  450  primes the autoinjector  400  right before use there is the advantage that this allows the autoinjector  400  to be stored and transported without stress, reducing the complexity of the autoinjector  400  and the risk of misfire and failure. 
     REFERENCE NUMBERS 
       100 ,  200 ,  300 ,  500  syringe 
       101 ,  201 ,  301 ,  351 ,  501 ,  510   a  housing 
       101   a  ratchet 
       101   b  return track 
       102 ,  202 ,  302 ,  402 ,  502  needle 
       105 ,  205 ,  305 ,  405 ,  505  first chamber 
       107 ,  207 ,  307 ,  407 ,  507  plunger 
       107   a  clip member 
       108  distal end section 
       109 ,  209 ,  309 ,  409 ,  509  second chamber 
       111 ,  511  lower piston 
       112 ,  512  upper piston 
       112   a  clip member 
       113  handle 
       114  through hole 
       115 ,  315 ,  415  needle boot 
       117  cotter pin 
       120  rib 
       122  needle 
       125  membrane 
       210  slug-like element 
       210   a  distal end 
       210   b  proximal end 
       211 ,  313 ,  413  seal 
       213  arrow 
       214  arrow 
       215  needle cover 
       220  element 
       250 ,  350 ,  450  base station 
       260  electromagnetic unit 
       260   a  electromagnetic coil 
       260   b  steel pole piece 
       262  line of magnetic field 
       265  opening 
       270  control unit 
       275  button 
       308 ,  408  vial 
       310 ,  410  supporting unit 
       310   a,    310   b,    410   a,    410   b  part of supporting unit 
       311 ,  411  first recess 
       312 ,  412  second recess 
       365 ,  465 ,  511   a  recess 
       366 ,  466  platform face 
       370 ,  470  drive unit 
       371 ,  471  transducer 
       372 ,  472  heater element 
       374  first linear slide 
       375  second linear slide 
       400  autoinjector 
       401  autoinjector body 
       414  air chamber 
       417  needle guard 
       418  septum 
       419  spring 
       420  locking mechanism 
       473  air pump 
       513  projection 
       530  compression spring 
       535  cap 
       536  clip mechanism 
       538  O-ring 
       540 ,  541 ,  542  arrow