Abstract:
There is provided drug delivery devices comprising a drug container assembly with a needle and automatic needle insertion and drug delivery mechanisms. Aspects of the devices described include a noise-generation mechanism to indicate the completion of drug delivery, a mechanism for triggering drug delivery following needle insertion, front-end activation of the device and a safety mechanism for covering the needle after use and methods of assembly of the devices.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to devices for administering drugs to patients, and in particular to autoinjectors. 
       BACKGROUND TO THE INVENTION 
       [0002]    An autoinjector is a drug delivery device that contains a medical, therapeutic, diagnostic, pharmaceutical or cosmetic compound (drug) before it is administered, and which is used to administer the compound through the skin of the patient via a hollow needle. Autoinjectors may be used by the patient themselves or by a different user, and may be used to administer drugs to animals. 
         [0003]    Autoinjectors are typically used because they reduce the amount of training and effort needed by a user compared with that needed for a syringe, by automating either or both processes of inserting the needle into the patient and expelling the drug through the needle. They can also reduce the fear of injection by hiding the needle from the patient and protect the patient from needle stick injuries. 
         [0004]    Autoinjectors typically include a housing containing a drug and a plunger that is driven by an automatic mechanism to move the plunger within the housing to eject the drug. The automatic mechanism may also move the needle relative to the housing to insert the needle into a subject. Motive power for the mechanisms may come from one or more springs or other power sources such as compressed gas. 
         [0005]    Autoinjectors are used to deliver so-called crisis drugs such as epinephrine, where a patient may need to self-inject the drug while under the severe stress of anaphylactic shock. They are also used to deliver drugs for long-term conditions such as rheumatoid arthritis, where the patient may have limited dexterity. 
         [0006]    In both cases it is beneficial for the autoinjector to have a simple and easy user interface in order to maximise the likelihood that the patient is able to operate the autoinjector correctly and receive the drug. It would also be desirable to provide an audible indication to the patient that drug delivery has been successfully completed. 
         [0007]    It is also desirable for the autoinjector to be small, reliable and robust, simple to manufacture, secure during transport and before intended use, and suitable for drugs having high viscosity. 
       SUMMARY OF THE INVENTION 
       [0008]    The invention is defined in the appended independent claims, to which reference should be made. Advantageous features are set out in the dependent claims. 
         [0009]    In a first aspect, there is provided a drug delivery device comprising:
       a drug container containing a drug;   a plunger within the drug container, movement of the plunger within the drug container being operative to deliver the drug from the drug container; and   a drive mechanism, the drive mechanism comprising: a stored energy source, the stored energy source configured to release energy by expanding from a compressed state, a first drive element coupled to the stored energy source, and a second drive element coupled to the first drive element and positioned between the first drive element and the plunger, wherein in a first position of the drive mechanism the first drive element is constrained from moving in an axial direction relative to the second drive element but in a second position of the drive mechanism the first drive element is free to move in the axial direction relative to the second drive element such that a first surface of the first drive element is driven against a first surface of the second drive element by the stored energy source to produce an audible signal indicative of the completion of drug delivery from the drug container.       
 
         [0013]    Previous mechanisms used to provide an audible indication of completion of drug delivery in drug delivery devices have suffered from the problem that the audible indication has not been loud enough. They have typically relied on a portion of the drive element used to drive the drug out of the device striking a stationary part of the device housing as it moves past that stationary part. The solution of the present invention is to use a stored energy source to drive two parts of a multi-part drive mechanism against each other when the drive mechanism reaches a predetermined position within the device. This allows a much greater noise to be generated as the parts can be made rigid and may be driven against each other at high speed. 
         [0014]    Advantageously the expansion of the stored energy source moves the drive mechanism from the first position to the second position. 
         [0015]    In order to constrain the first drive element from moving in the axial direction relative to the second drive element in the first position, a further component within the drive mechanism, which interacts with an external component of the device, may be used. Alternatively, an external component of the housing through which the drive mechanism moves may be used to interact with the first or second drive element to constrain relative axial movement between the first and second drive element. 
         [0016]    In some embodiments, the drive mechanism may comprise a third drive element, the third drive element constraining relative movement between the first drive element and the second drive element when the drive mechanism is in the first position, wherein the third drive element is configured to engage the drug container or a portion of a housing of the drug delivery device as the drive mechanism moves to the second position. 
         [0017]    The third drive element may be configured to engage the drug container or a portion of the housing of the drug delivery device at a release position between the first position and the second position of the drive mechanism, and, as the drive mechanism moves from the release position to the second position, the third drive element may be held stationary relative to the drug container or housing to release the first or second drive member from the third drive member. The third drive element may be positioned between the first and second drive elements. 
         [0018]    It is important that the first surface of the first drive element is driven against the first surface of the second drive element reliably and at the correct time, which is when the drug has been fully (or almost fully) expelled from the drug container by the drive mechanism. There are inevitably some small variations in the dimensions of the component parts of the device from one device to the next, no matter what manufacturing process is used. An advantage of configuring the third element to engage the drug container directly is that it means that relatively few separate components are involved in determining when the first drive element is driven against the first surface of the second drive element, so the requirement for very fine dimensional tolerances for each component is reduced, and the timing of the audible indication can more closely match the end of drug delivery. 
         [0019]    In the first position of the drive mechanism, the first drive element and the second drive element may be constrained from relative rotation. In the second position of the drive mechanism the first drive element and the second drive element may be free to rotate relative to one another and, following or during relative rotation, may move in an axial direction relative to one another. 
         [0020]    The first drive element may comprise a first bearing surface, and the second drive element may comprise a second bearing surface engaging the first bearing surface in the first position of the drive mechanism, wherein rotation of the first drive element relative to the second drive element moves the first bearing surface off the second bearing surface, allowing the first surface of the first drive element to strike the first surface of the second drive element, wherein in the first position of the drive mechanism, the third drive element constrains relative rotation between the first drive element and the second drive element, and in the second position, the third drive element is moved axially relative to the first and second drive elements to a position in which the third drive element does not constrain relative rotation between the first drive element and the second drive element. 
         [0021]    The second drive element may comprise a first axially extending protrusion or slot that in the first position engages the third drive element to prevent relative rotation between the second drive element and the third drive element, and the first drive element may comprise an axially extending slot or protrusion that in the first position engages with the third drive element to prevent relative rotation between the third drive element and the first drive element. 
         [0022]    The third drive element may extend around at least a portion of the second drive element and the first drive element may extend around at least a portion of the third drive element. The first and third drive elements may be generally tubular. 
         [0023]    Alternatively, or in addition, the drug delivery device may comprise a housing component coupled to or integral with the drug container, the housing component constraining the first drive element from moving relative to the second drive element in the first position of the drive mechanism. The drug delivery device may further comprise an external housing, wherein the drug container is configured to move through the external housing during operation of the device, and wherein the housing component moves through the external housing with the drug container. The drug delivery device may comprise a hypodermic needle and the housing component may be part of a needle insertion mechanism that moves the drug container through the housing to insert the needle into an injection site. 
         [0024]    The drug delivery device may be an autoinjector. 
         [0025]    In a second aspect, there is provided a drug delivery device comprising:
       a housing;   a drug container, and   an powerpack assembly coupled to the drug container, the powerpack assembly comprising:
           a stored energy source, the stored energy source configured to release energy by expanding from a compressed state;   an insertion member engaging the stored energy source and positioned between the stored energy source and the drug container; and   a retaining means, in a first position the retaining means engaging the stored energy source and the insertion member to retain the stored energy source in a first compressed state;   
           wherein the retaining means and housing are configured such that the retaining means is moved by the housing to a second position on engagement of the powerpack assembly with the housing, the retaining means being disengaged from the stored energy source or the insertion member in the second position;   the drug container and housing being configured such that the stored energy source is retained in a second compressed state by the drug container when the retaining means is moved to the second position, and   a triggering mechanism configured to release the stored energy source from the second compressed state when the autoinjector is to be used.       
 
         [0035]    The housing may comprise a first cam surface configured to engage a second cam surface on the retaining means. The retaining means and housing may be configured such that the retaining means is rotated by the housing to the second position on engagement of the powerpack assembly with the housing. 
         [0036]    The stored energy source may be a compression spring or a gas spring, for example. 
         [0037]    The drug delivery device may further comprise a drive mechanism configured to drive a plunger through the drug container, the drive mechanism comprising a second stored energy source, and a release mechanism configured to control a sequence of release of the first stored energy source and the second stored energy source, wherein the retaining means forms a part of the release mechanism. 
         [0038]    The drive mechanism may be configured to drive the drug container through the housing in a longitudinal direction, and wherein the retaining means comprises a longitudinally extending retaining limb that retains a drive element of the drive mechanism to the insertion member to prevent a release of the second stored energy source. The retaining limb may be configured to release the drive element from the insertion member substantially at an end of travel of the drug container through the housing. The retaining means and housing may be configured such that the retaining means is rotated about a longitudinal axis by the housing to the second position. 
         [0039]    The retaining means may be held within the housing and is inaccessible to a user during use. As used herein, the axial direction, the longitudinal direction and the insertion direction are used to mean the same direction. 
         [0040]    Prior to use of the device, the first stored energy source may be positioned at least partially within the second stored energy source. The insertion element may comprise a first portion comprising a bearing surface engaging the first stored energy source, and a second portion extending from the first portion, the second portion defining a recess in which the second stored energy source is received. 
         [0041]    The insertion element may be assembled from two components to simplify manufacture and assembly of the device. 
         [0042]    The drive member may comprise a mechanism for providing an audible indication in accordance with the first aspect of the invention. 
         [0043]    The drug container may be retained by one or more latches on the housing or on an internal component coupled to the housing, to retain the stored energy source in the second compressed state. 
         [0044]    The triggering mechanism may comprise a movable skin sensor element, configured such that when the skin sensor element is pressed onto an injection site, the skin sensor element moves to release the drive means from the second deformed condition. 
         [0045]    The drug delivery device may be an autoinjector. 
         [0046]    In a third aspect of the invention there is provided a method for assembling a drug delivery device according to the second aspect of the invention, comprising the steps of:
       placing or forming a stored energy source in a powerpack assembly having a powerpack housing;   retaining the stored energy source in the powerpack assembly in a first compressed condition using a retaining means coupled to the drive member and the powerpack housing in a first position;   coupling the powerpack assembly to a drug container assembly, the drug container assembly containing a drug to be dispensed by the autoinjector;   coupling the powerpack assembly and drug container assembly to an outer housing; and   moving the retaining means to a second position to release the stored energy source to second compressed condition, wherein the drug container assembly and outer housing retain the stored energy source in the second compressed condition and wherein in the second compressed condition the stored energy source stores sufficient potential energy for needle insertion and/or drug ejection when the autoinjector is to be used.       
 
         [0052]    The step of moving the retaining means may be performed as a consequence of the step of coupling to the outer housing. 
         [0053]    The step of moving the retaining means may comprise rotation of the retaining means relative to the powerpack housing. 
         [0054]    In a fourth aspect, there is provided a drug delivery device comprising:
       a device housing;   a drug container within the housing and containing a drug, and a plunger positioned within the drug container, the drug container having an outlet for dispensing the drug; and   a powerpack assembly, the powerpack assembly comprising an insertion member fixed to or abutting the drug container, a first stored energy source positioned between the insertion member and the device housing, and a second stored energy source positioned between the insertion member and a drive member, wherein, in use, the drive member is configured to engage the plunger, wherein, in an initial position, the first stored energy source is located at least partially within the second stored energy source.       
 
         [0058]    The insertion member may be driven by the first stored energy source to move the drug container through the housing and the drive member may be driven by the second stored energy source to move the plunger through the drug container. 
         [0059]    The second stored energy source may be held within the insertion member before operation of the device. 
         [0060]    The insertion member may comprise a first portion comprising a first bearing surface engaging the first stored energy source, and a second portion extending from the first portion, the second portion defining a recess in which the second stored energy source is received. The first or second portion of the insertion member may comprise a second bearing surface engaging the drive member. 
         [0061]    The drug delivery device may further comprise a retaining means, the retaining means coupled to the device housing, and extending within the first stored energy source and engaging the drive member or the insertion member to prevent the drive member from disengaging from the second bearing surface. The device may be configured such that movement of the insertion member through the housing to an insertion position releases the drive member from the retaining means. 
         [0062]    The first stored energy source may be configured to expand to release energy to drive the insertion member within the device housing and the first stored energy source may be initially prevented from expanding by the engagement of a portion of the device housing with the drug container. 
         [0063]    The drug delivery device may be an autoinjector. 
         [0064]    In a fifth aspect of the invention, there is provided a drug delivery device, comprising:
       a drug container;   an internal housing;   an insertion mechanism coupled to the drug container and configured to move the drug container through the internal housing in an insertion direction;   a skin sensor element, configured to contact an injection site in use; and   a skin sensor biasing element biasing the skin sensor in the insertion direction;   wherein the skin sensor element is movable in a direction opposite to the insertion direction from an initial position to a retracted position to trigger the insertion mechanism;   wherein the internal housing includes a first latching element to restrain the skin sensor element from moving from the initial position in the insertion direction, wherein the first latching element comprises a latching surface configured to engage the skin sensor element and a first camming surface; and   wherein either the drug container or the insertion mechanism includes a second camming surface, wherein the second camming surface is configured to engage the first camming surface to move the first latching element as the drug container is moved through the internal housing in the axial direction, thereby allowing the skin sensor element to move in the insertion direction past the initial position to an extended position. In the extended position the skin sensor element covers the needle.       
 
         [0073]    The first latching element may comprise a resilient cantilever arm, wherein the latching surface and the first camming surface are formed at a free end of the cantilever arm. The cantilever arm may be held in tension by the skin sensor element and skin sensor biasing element when the skin sensor is in the initial position. 
         [0074]    The internal housing may define a central bore through which the drug container moves, and the first and second camming surfaces may be configured to move the latching element in a direction parallel to a perimeter of the bore. The first camming surface may be positioned inwardly of the latching surface. The first camming surface advantageously extends non-parallel with the latching surface. Inwardly in this context means further from an exterior surface of the device. 
         [0075]    The skin sensor element may comprise at least a first aperture that aligns with a drug container latch on the internal housing when the skin sensor element is in the retracted position. 
         [0076]    The skin sensor may be configured so as not to occlude a window in the internal housing for viewing the drug container when in the initial or retracted position. 
         [0077]    The drug delivery device may further comprise a second latching element formed on the internal housing, the second latching element being configured to prevent the skin sensor moving to the retracted position after it has been released from the first latching element. The second latching element may engage a second aperture or a protrusion on the skin sensor element. 
         [0078]    In the retracted position the skin sensor element may abut the internal housing to prevent further movement of the skin sensor element relative to the internal housing in a direction opposite to the insertion direction. 
         [0079]    The drug delivery device may be an autoinjector. 
         [0080]    In a sixth aspect of the invention there is provided a needle assembly comprising:
       a hypodermic needle;   a needle hub to which the needle is fixed at a first end;   a needle shield coupled to the needle hub and covering a second end of the needle; wherein the needle shield comprises a rigid body, the rigid body providing a sterile barrier around at least a portion of the needle; and   a compliant element within the rigid body, the compliant member providing a liquid tight seal around a second end of the needle,   wherein the rigid body is configured to provide an interference fit with the needle hub and thereby provides a seal around the needle hub.       
 
         [0086]    The rigid body may be formed from a moulded plastics material, such as high-density polyethylene or polypropylene. 
         [0087]    The needle assembly may comprise at least one circumferential rib on an interior surface of the rigid body or on an external surface of the needle hub. Preferably, the needle assembly comprises at least two circumferential ribs on the interior surface of the rigid body. The radius of curvature of each rib at the contact point, prior to fitting of the rigid body to the needle hub is preferably less than 0.6 mm. The contact point of each rib is the point on the surface of the rib that is configured to first contact the needle hub when the rigid body is fitted to the needle hub. 
         [0088]    The needle hub may be formed from a moulded plastics material, such as cyclic olefin polymer. The needle hub may have a surface finish having a maximum distance between peak and trough of 2 μm or less. Preferably, a surface finish of the needle hub is 0.2 Ra or less. The needle hub may have a circular cylindrical outer surface to which the rigid body is coupled. An interior surface of the rigid body preferably has a surface finish of 0.2 Ra or less. An interior surface of the rigid body may have a surface finish having a maximum distance between peak and trough of 2 μm or less. 
         [0089]    The rigid body may comprise an external surface having at least one protrusion or recess. At least a portion of the rigid body may be transparent. 
         [0090]    The compliant element may be fully enclosed, or may be only partially enclosed, by the rigid body and needle hub. The compliant element may be retained in the rigid body by at least one protrusion on the rigid body. 
         [0091]    The needle assembly may further comprise at least one vent in the compliant element or the rigid body for allowing air to escape from the rigid body during insertion of the compliant element into the rigid body. Alternatively, the rigid body may be moulded over the compliant element, or the compliant element may be moulded inside the rigid body. 
         [0092]    In a seventh aspect of the invention, there is provided an autoinjector or syringe comprising a needle assembly in accordance with the sixth aspect. 
         [0093]    In an eighth aspect of the invention, there is provided a method of manufacturing a needle assembly comprising:
       fixing a first end of a needle to a needle hub; and   coupling a needle shield to the needle hub, the needle shield covering a second end of the needle; wherein the needle shield comprises a rigid body and a complaint element, wherein the rigid body is configured to provide an interference fit with the needle hub and thereby provide a seal around the needle hub, the rigid body providing a sterile barrier around at least a portion of the needle, the step of coupling including inserting a second end of the needle into the compliant element such that the compliant element provides a liquid tight seal around the second end of the needle.       
 
         [0096]    In a ninth aspect of the invention, there is provided a drug delivery device comprising:
       a drug container assembly comprising a drug container containing a drug, a hypodermic needle coupled to the drug container and through which the drug can be dispensed and a plunger within the drug container;   an internal housing, the drug container positioned within the internal housing and movable through the internal housing;   a powerpack assembly comprising at least one stored energy source, the powerpack assembly coupled to the drug container;   a lower housing fixed to the internal housing;   an upper housing fixed to the lower housing and enclosing the powerpack assembly;   a skin sensor element extending between the lower housing and the internal housing and movable relative to the internal housing and the lower housing; and   a cap covering the skin sensor element and coupled to the lower housing.       
 
         [0104]    The upper housing may be fixed to the lower housing using one or more mechanical fixings. 
         [0105]    The device may be configured such that movement of the skin sensor element relative to the internal housing from an initial position to a retracted position releases the stored energy source within the powerpack assembly. 
         [0106]    The internal housing may comprise retaining latches, which, when the skin sensor element is in the initial position, are engaged with the drug container to retain the drug container in an initial position of the drug container to retain the stored energy source, and wherein movement of the skin sensor element to the retracted position allows the retaining latches to disengage from the drug container, thereby releasing the stored energy source. 
         [0107]    The internal housing may comprise first latching elements that restrain the skin sensor element from movement out of the initial position. The first latching elements may be resilient arms that engage the skin sensor element at a free end. 
         [0108]    The lower housing or internal housing may comprise second latching elements that lock the skin sensor element in an extended position after the skin sensor has moved to the extended position. 
         [0109]    The powerpack assembly may comprise first and second stored energy sources, wherein the first stored energy source provides energy to move the drug container from an initial position of the drug container to an insertion position of the drug container, and wherein the second stored energy source provides energy to move the plunger within the drug container to dispense the drug. The powerpack assembly may be fixed to the drug container. The stored energy sources may be compression springs. 
         [0110]    The powerpack assembly may comprise a retaining means in accordance with the second aspect of the invention. The powerpack may comprise a drive mechanism in accordance with the first aspect of the invention. 
         [0111]    The internal housing may comprise a stopping surface configured to engage the drug container as the drug container moves to an insertion position. The stopping surface may comprise one or more resilient cantilever beams that are deformed by the drug container as the drug container moves to an insertion position. 
         [0112]    The cap may directly or indirectly engage the skin sensor element, to prevent the skin sensor element from moving to a retracted position from an initial position. 
         [0113]    The upper housing or lower housing may comprise an aperture to allow for viewing of the drug. The internal housing or the lower housing may be transparent and may be configured to engage the aperture in upper housing. 
         [0114]    The upper housing may comprise two major surfaces each including an aperture to allow for viewing of the drug, and two minor surfaces. The first and second latching elements may be positioned adjacent a minor surface of the upper housing. 
         [0115]    The drug delivery device may be an autoinjector. 
         [0116]    In a tenth aspect of the invention, there is provided a method of assembling a drug delivery device according to the ninth aspect, comprising the steps of:
       providing the powerpack assembly;   providing the drug container assembly;   providing a front end assembly comprising the internal housing, the lower housing and the skin sensor and the cap;   providing the upper housing;   coupling the powerpack assembly to the drug container assembly;   coupling the drug container assembly to the front end assembly; and   coupling the powerpack assembly, drug container assembly and front end assembly to the upper housing.       
 
         [0124]    The step of coupling the powerpack assembly to the drug container assembly may be performed before or after the step of coupling the drug container assembly to the front end assembly. Similarly, the cap may be coupled to the other elements of the front end assembly at any point in the method. 
         [0125]    In an eleventh aspect of the invention, there is provided a drug delivery device comprising;
       a housing;   a drug container within the housing,   a powerpack assembly configured to move the drug container through the housing in an axial direction from an initial position to an insertion position,   wherein the housing includes a stopping surface configured to engage the drug container when the drug container reaches the insertion position, wherein the stopping surface is provided on a least one resilient beam on the housing, the resilient beam being deflectable in the axial direction.       
 
         [0130]    The stopping surface may be provided on a pair of cantilever beams. The device may comprise an outer housing and an internal housing, and the stopping surface is provided on the internal housing. 
         [0131]    The drug container may comprise a hypodermic needle. 
         [0132]    The drug delivery device may be an autoinjector. 
         [0133]    In a twelfth aspect of the invention, there is provided a drug delivery device comprising;
       a housing;   a drug container within the housing and containing a drug to be dispensed, the drug container having a first end defining a first opening;   a plunger, positioned within the drug container, in contact with the drug;   a first sealing element providing a first closure seal across the first opening of the drug container;   a pusher initially located on an opposite side of the first closure seal to the plunger, wherein the pusher is operable to break the first closure seal and move the plunger within the drug container to dispense the drug; and   an insertion mechanism configured to move the drug container through the housing,   wherein, prior to use, the pusher and the insertion mechanism are held out of contact with the first sealing element.       
 
         [0141]    The sealing element may be laminated foil and may be welded or glued to the drug container. The term “closure seal” as used herein in the claims and description means a seal that prevents deterioration or contamination of a drug in a container against foreseeable external factors in storage. A closure seal maintains the safety, identity, strength, quality, sterility and/or purity of a drug in a container in compliance with official, regulatory or established requirements. 
         [0142]    The drug container may comprise a second opening through which the drug is dispensed and at least one side wall extending between the first opening and the second opening, wherein the drive mechanism is engaged to the at least one sidewall. 
         [0143]    The drug delivery device may be an autoinjector. 
         [0144]    In a thirteenth aspect there is provided a drug delivery device comprising;
       a housing;   a drug container within the housing and containing a drug to be dispensed, the drug container having a first end defining a first opening;   a plunger, positioned within the drug container, in contact with the drug;   a first sealing element providing a first closure seal across the first opening of the drug container;   a pusher initially located on an opposite side of the first closure seal to the plunger, wherein the pusher is operable to break the first closure seal and move the plunger within the drug container to dispense the drug; and   an insertion mechanism configured to move the drug container through the housing prior to operation of the pusher to break the first closure seal,   wherein, no elements of the insertion mechanism and housing contact the first sealing element as the drug container is moved through the housing.       
 
         [0152]    The drug delivery device may be an autoinjector. 
         [0153]    Features described in relation to one aspect of the invention may equally be applied to any other aspect of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0154]    Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which: 
           [0155]      FIG. 1  is a perspective view of an autoinjector in accordance with a first embodiment of the invention, prior to use; 
           [0156]      FIG. 2  is a first cross-section through the autoinjector of  FIG. 1 ; 
           [0157]      FIG. 3  is a second cross-section through the autoinjector of  FIG. 1 ; 
           [0158]      FIG. 4 a    is a perspective view of the drug container assembly; 
           [0159]      FIG. 4 b    is a cross-section view of the drug container assembly; 
           [0160]      FIG. 5  is a cross-section showing the needle shield and the needle hub of the drug container; 
           [0161]      FIG. 6 a    is a first partial cross-section of the powerpack housing; 
           [0162]      FIG. 6 b    is a second partial cross-section of the powerpack housing; 
           [0163]      FIG. 7  is a top perspective view of the powerpack assembly; 
           [0164]      FIG. 8  is a perspective view of the drive member in an initial configuration; 
           [0165]      FIG. 9  is a perspective view of the drive member in a final configuration, after drug delivery; 
           [0166]      FIG. 10  is a perspective view of the skin sensor element; 
           [0167]      FIG. 11  is a perspective view of the internal housing; 
           [0168]      FIG. 12  is a perspective view of lower housing; 
           [0169]      FIG. 13 a    is a side view of the device with the upper housing and cap removed, showing the skin sensor element in an initial position; 
           [0170]      FIG. 13 b    is a side view of the device with the upper housing and cap removed, showing the skin sensor element in a retracted position; 
           [0171]      FIG. 13 e    is a side view of the device with the upper housing and cap removed, showing the skin sensor element in a retracted position and with the skin sensor latching element deflected by the powerpack assembly; 
           [0172]      FIG. 13 d    is a side view of the device with the upper housing and cap removed, showing the skin sensor element and powerpack assembly in a final position; 
           [0173]      FIG. 14  is a perspective view of the cap; 
           [0174]      FIG. 15  is a cross-section view of the front end of the device prior to removal of the cap; 
           [0175]      FIG. 16 a -16 g    are cross-section views of the first embodiment, illustrating the sequence of operation; 
           [0176]      FIG. 17  is a schematic diagram illustrating the assembly process of an autoinjector in accordance with the first embodiment of the invention; 
           [0177]      FIG. 18  is a perspective view of an autoinjector in accordance with a second embodiment of the invention, prior to use; 
           [0178]      FIG. 19  is a first cross-section through the autoinjector of  FIG. 18 ; 
           [0179]      FIG. 20  is a second cross-section through the autoinjector of  FIG. 18 ; 
           [0180]      FIG. 21  is a perspective view of the drug container assembly of the second embodiment; 
           [0181]      FIG. 22  is a perspective view of the powerpack housing of the second embodiment; 
           [0182]      FIG. 23  is a perspective view of a skin sensor element of the second embodiment; 
           [0183]      FIG. 24  is a perspective view of a chassis of the second embodiment; 
           [0184]      FIGS. 25 a  to 25 c    are side views of the skin sensor element, chassis and powerpack housing showing the sequence of movement of the skin sensor element during use; 
           [0185]      FIG. 26  is a perspective view of the lower housing of the second embodiment; 
           [0186]      FIG. 27  is a perspective of the cap of the second embodiment; 
           [0187]      FIGS. 28 a  to 28 e    are cross-section views of the second embodiment, illustrating the sequence of operation; 
           [0188]      FIG. 29  is a schematic diagram illustrating the assembly process of an autoinjector in accordance with the second embodiment of the invention; and 
           [0189]      FIG. 30  illustrates the mechanism by which the powerpack is disengaged from the outer housing as it engages the chassis. 
       
    
    
     DETAILED DESCRIPTION 
       [0190]      FIG. 1  is a perspective view of an autoinjector  1  in accordance with a first embodiment of the invention, before use. The autoinjector comprises an outer housing  20 , having a viewing window  22  through which a drug within the autoinjector can be inspected. A cap  30  is provided to cover the end of the device through which the needle passes during operation and to prevent inadvertent activation of the device. The autoinjector is compact, being approximately 10 cm long and fits easily in a user&#39;s hand. 
         [0191]      FIG. 2  is a cross-sectional view through the autoinjector  1  of  FIG. 1 .  FIG. 3  is a second cross-sectional view through the autoinjector of  FIG. 1 , at 90 degrees to the cross-section of  FIG. 2 . 
         [0192]    The autoinjector  1  shown in  FIGS. 1, 2 and 3  comprises a drug container assembly (shown in  FIGS. 4 a  and 4 b   ), a powerpack assembly (shown partially in  FIGS. 6 a , 6 b    and  7 ) including an end of delivery noise generating mechanism (shown in  FIGS. 8 and 9 ), an internal housing (shown in  FIG. 11 ), herein referred to as the chassis, a skin sensor assembly comprising a skin sensor element (shown in  FIG. 10 ) and a skin sensor spring, a lower housing (shown in  FIG. 12 ), an outer housing and a cap (shown in  FIG. 14 ). 
         [0193]    The drug container assembly  10  is held within the chassis  120  and in operation moves through the chassis. The drug container assembly  10  is retained in an initial position by latches  122  on the chassis, which engage protrusions  13  on the drug container and which are prevented from releasing the drug container by the skin sensor assembly. The skin sensor assembly comprises a skin sensor element  112  and a skin sensor spring  114 . The skin sensor element is held by latching elements  124  on the chassis  120  and urged away from the drug container assembly  10  by the skin sensor spring  114 , which is held between the chassis  120  and the skin sensor element  112 . The lower housing  140  engages the chassis  120  by clipping to a window portion  130  of the chassis. Lugs  148  on the lower housing engage recesses  24  formed in the outer housing. The cap  30  engages recesses  142  on the lower housing and covers the skin sensor element  112 . 
         [0194]    The drug container assembly is shown alone in  FIG. 4 a   .  FIG. 4 b    is a cross-section view of  FIG. 4 a   . The drug container assembly comprises a drug container  10  containing a drug to be delivered to a patient by injection, with a hypodermic needle  12  fixed to a front end. The drug container is formed from cyclic olefin, which has excellent drug contact properties. The use of a plastic drug container has several advantages over glass. A plastic container can be moulded with features that form part of the automatic injection and drug delivery mechanism, as described in relation to this embodiment below, and can be formed with much higher accuracy than glass, A plastic container can also withstand higher impact forces and pressures allowing for the use of more powerful springs in the autoinjector mechanism and for a shorter, fatter drug container. 
         [0195]    A plunger  14  is provided within the drug container. Movement of the plunger  14  within the drug container  10  urges the drug out through the needle  12 . The plunger is designed to provide low friction with the walls of the drug container and to minimise any station between the plunger and the drug container. The plunger is a cup seal type plunger, configured such that a component of the fluid pressure exerted by the drug on the plunger as the plunger is moved through the drug containers is directed towards a sealing interface between the plunger and an internal surface of the drug container. A plunger of this type is described in GB2467904. A peripheral portion of the plunger  14  in contact with a wall of the drug container comprises a substantially non-elastomeric material. The internal surface of the front end of the drug container  10  is shaped to match the shape of the front end of the plunger  14  to maximise the amount of drug that is pushed out of the drug container during use. 
         [0196]    A sealing foil  16  is provided at a back end of the drug container  10  to ensure the drug is retained and maintained in a sterile and pristine condition. The sealing foil  16  may be laminated foil including a layer of aluminium and may be welded or glued to a back end of the drug container  10 . 
         [0197]    In this embodiment, the hypodermic needle  12  is glued into a needle hub portion  11  of the drug container  10 . However, the drug container may be moulded around the needle. The needle is covered by a needle shield  50  that keeps the needle  12  sterile. As shown in  FIG. 4 b   , the needle shield  50  comprises a rigid outer housing  52  that forms a seal with the needle hub portion  11 . A compliant element in the form of an elastomeric plug  54  is provided within the needle shield into which the front end of the needle  12  is inserted. The elastomeric plug seals the needle and ensures that no drug can escape from the needle prior to removal of the needle shield. The rigid outer housing  52  of the needle shield may be transparent to allow for inspection of the needle during assembly of the autoinjector. The front end of the rigid outer housing  52  comprises a bulb  56  configured to engage hooks  32  in the cap  30 , as shown in  FIG. 2 a   . This ensures that when the cap  30  is removed the needle shield is removed with it. 
         [0198]    The sealing of the needle shield to the needle hub  11  is shown in detail in  FIG. 5 , which is close-up view of a portion of  FIG. 4 b   . The needle hub  11  is cylindrical where it surrounded by the needle shield. The rigid body  52  of the needle shield has a pair of ribs  57 ,  58  that extend around the inner surface of the needle shield. The ribs have an interference fit with the needle hub  11  to provide a seal that maintains the needle sterile. In this example, the hub has a diameter of 2.4 mm and a surface finish quality where the maximum distance between peak and trough is no more than 2 μm. The needle hub may be formed from a moulded plastics material, such as cyclic olefin polymer. The surface finish of the needle hub is specified to 0.2 Ra. The needle hub may have a circular cylindrical outer surface to which the rigid body is coupled. An interior surface of the rigid body is specified to have a surface finish of 0.2 Ra or less. An interior surface of the rigid body may have a surface finish having a maximum distance between peak and trough of 2 μm or less. The ribs have a nominal sealing diameter of 2.2 mm. There is therefore a nominal diametrical interference between the needle hub  11  and the needle shield  50  of 0.2 mm. 
         [0199]    The rigid body of the needle shield is formed from polyethylene and has the same surface finish as the needle hub. The ribs  57 ,  58  are spaced from one another by 3 mm. In order to provide the greatest contact pressure between the ribs and the needle hub, combined with the lowest force, and so the tightest seal with the lowest removal force, the contact area between the ribs and the needle hub should be a small as possible. However, the contact area is limited by the manufacturing process for the needle shield and the materials used. In this example, the radius of curvature of each rib at the contact point, prior to fitting of the rigid body to the needle hub is preferably less than 0.6 mm. The contact point of each rib is the point on the surface of the rib that is configured to first contact the needle hub when the rigid body is fitted to the needle hub. However, the final contact radius may be larger than this, particularly if the plastic is deformed by the interference. 
         [0200]    The autoinjector shown in  FIGS. 1 to 3  also comprises an automatic mechanism for inserting the needle into an injection site and for ejecting the drug through the needle into the injection site. The automatic mechanism is referred to herein as the powerpack assembly. The powerpack assembly comprises stored energy sources, in the form of compressed springs  61 ,  62 . When the first spring  61 , referred to as the insertion spring, is released it moves the drug container  10  through the housing of the autoinjector to insert the needle  12  into an injection site. The second spring  62 , referred to as the delivery spring, is then released to move the plunger  14  through the drug container  10  to inject the drug. The springs  61 ,  62  and the mechanism for controlling a sequence of release of the springs within the powerpack assembly are positioned rearward of the drug container. 
         [0201]    The powerpack comprises a powerpack housing  64  that is coupled to the drug container  10 . The powerpack housing of this embodiment comprises two parts, a lower powerpack housing  65  and an upper powerpack housing  66 . The powerpack housing is in two parts to simplify the assembly of the autoinjector, but, in use, the two parts are fixed to each other and act as a single component. The lower powerpack housing  65  is clipped to the drug container  10 . The lower powerpack housing  65  engages recesses  17  on the drug container. The insertion spring  61 , shown in  FIGS. 2 and 3  in a compressed condition prior to use of the autoinjector, is positioned between the upper powerpack housing  66  and a retaining means  100 . The retaining means  100  is coupled to the upper powerpack housing  66  to retain the insertion spring  61  in a first compressed condition, as is explained with reference to  FIG. 7 . 
         [0202]    The delivery spring  62  is positioned between the upper powerpack housing  66  and a multiple component drive member  70 . When released, the delivery spring  62  drives the drive member  70  forward relative to the powerpack housing  64  and so drives the plunger  14  through the drug container  10  to eject the drug, as is described in detail below. 
         [0203]    Before use of the autoinjector, the delivery spring  62  is positioned around the insertion spring  61 . A two-spring mechanism, nested in this way has advantages. Firstly, by nesting one spring within the other, the length of the autoinjector is minimised. Secondly, the delivery spring can be made larger than the insertion spring. The force required to eject the drug through the needle is typically much greater than the force required to insert the needle into an injection site. The use of a smaller spring for needle insertion is therefore beneficial. 
         [0204]    The rear end of the powerpack assembly is shown in detail in  FIGS. 6 a  and 6 b   ).  FIG. 6 a    is a first cross-section through the powerpack assembly and shows the insertion spring seated on a first ledge  67  formed on the upper powerpack housing  66 .  FIG. 6 b    is a second cross-section through the powerpack assembly, at ninety degrees to the cross-section of  FIG. 6 a   , and shows the drive member  70  retained by a second ledge  69  formed on the upper powerpack housing. 
         [0205]    The powerpack assembly is assembled as a separate component before it is coupled to the drug container and the rest of the autoinjector. In order to retain the insertion spring and delivery spring in a compressed condition, the powerpack housing engages the retaining means  100 . The retaining means comprises a head portion  106  and a shaft portion  108  that extends from the head portion within the powerpack housing  64  and the drive member  70 . The shaft portion  108  ensures that the drive member  70 , and in particular lobes  86  on the second drive element  80 , cannot disengage from the ledge  69  on the powerpack housing until the drive member is moved clear of the shaft portion  108 . 
         [0206]      FIG. 7  is a partial, perspective top view of the powerpack assembly, showing the retaining means  100  engaging the upper powerpack housing  66 . The insertion spring  61  urges the powerpack housing away from the retaining means  100  but it is retained by the engagement of surfaces  102  on the retaining means under shelves  68  formed on the upper powerpack housing. The powerpack housing is released from the retaining means  100  by relative rotation between the powerpack housing and the retaining means. In particular, cam surfaces  104  are formed on the retaining means so that when the powerpack assembly is inserted into the outer housing, cam surfaces or protrusions  25  within the outer housing engage the cam surfaces on the retaining means and force the retaining means to rotate. The powerpack housing is prevented from rotating relative to the outer housing by engagement of the powerpack housing with the chassis and engagement of the chassis with the outer housing. The rotation of the retaining means  100  moves surfaces  102  out of engagement with shelves  68  so that the powerpack housing is disengaged from the retaining means. 
         [0207]    Once the powerpack housing has been released from the retaining means  100  it is prevented from fully expanding by the engagement of the outer housing  20  with the lower housing  140 , the engagement of the lower housing  140  with the chassis  120 , the engagement of the chassis  120  with the drug container  10  and the engagement of the drug container  10  to the powerpack housing  64 . The outer housing  20  is configured to engage the lower housing  140  as it drives the retaining means  100  out of engagement with the powerpack housing by rotating the retaining means. 
         [0208]    As described, the insertion spring  61  engages the ledge  67  on the upper powerpack housing  66  to drive the powerpack housing and drug container assembly forward through the chassis as it expands. The drive spring  62  engages the powerpack housing  64  and the drive member  70  to drive the drive member and plunger through the drug container. The drive member  70  comprises three components. Specifically, the drive spring engages a spring bearing surface  72  on a first drive element  71 . The first drive element  71  is coupled to a second drive element  80  and a third drive element  90 . The multiple element drive member  70  is shown in  FIGS. 8 and 9 . 
         [0209]    The drive member  70  is shown in an initial configuration in  FIG. 8 , prior to delivery of the drug from the drug container. The first drive element  71  is essentially a circular cylindrical tube, within which a second drive element  80  is located. A first striking surface  75  on the first drive element is held apart from a first striking surface  85  on the second drive element by the engagement of the first drive element with a tooth  84  that extends from the first striking surface on the second drive element towards the first drive element. The second drive element comprises a foil contact surface  82  configured to contact and pierce the sealing foil  16  on the drug container  10 . The foil contact surface  82  comprises a plurality of serrations to assist in piercing the foil seal. The second drive element  80  extends from the first striking surface  85 , through the first drive element. 
         [0210]    The second drive element is formed from a moulded plastics material and is divided at its rear end into a pair of flexible legs  87 , at the rear end of each of which a lobe  86  is formed for engagement with the powerpack housing. A bore  88  is defined between the legs, into which the shaft portion  108  of the retaining means is received. The shaft portion of the retaining means prevents the legs  87  from deflecting inwardly to disengage from the ledge  69  on the upper powerpack housing. 
         [0211]    The first drive element  71  comprises a cut-out  73  that is dimensioned to receive tooth  84  of the second drive element so that the first striking surface  75  on the first drive element and contact the first striking surface  85  on the second drive element. In order for tooth  84  to be received in the cut-out  73  the first drive element must be rotated relative to the second drive element. However, in an initial position, this is prevented by the third drive element  90 . The third drive element  90  engages both the first drive element and the second drive element in the initial position. The third drive element in this embodiment is generally tubular and is positioned between the first drive element and the second drive element. A protrusion  92  on the third drive element engages a slot  74  formed in the first drive element to prevent relative rotation of the first drive element and the third drive element. The slot is dimensioned to allow axial movement i.e. movement in the direction of travel of the drive member on expansion of the drive spring, between the first drive element and the third drive element. A cut-out  94  in the third drive element engages the tooth  84  on the second drive element to prevent relative rotation between the second drive element and the third drive element. However, the third drive element is free to move axially relative to the second drive element. 
         [0212]    As the drive member reaches the end of its forward travel through the drug container, the protrusion  92  on the third drive element engages a rear surface of the drug container  10 . The third drive element is thus held by the drug container as the first and second drive elements continue to move forwards under the influence of the drive spring  62 . When the cut-out  94  in the third drive element is disengaged from the tooth  84  as a result of the this relative axial movement between the third drive element and the second drive element, the first drive element  71  is free to rotate relative to the second drive element  80 . Tooth  84  engages the first drive element on an angled surface  76  so that the action of the drive spring on the first drive element  71  forces it to rotate relative to the second drive element. When the tooth  84  is free to enter cut-out  73 , the first drive element moves forward rapidly relative the second drive element as there is no significant resistance to that forward movement. The first striking surface on the first drive element then strikes the first striking surface on the second drive element at high speed, creating an audible single indicative of the drive member reaching the end of its travel. The final position is shown in  FIG. 9 . 
         [0213]    A principle of operation of this “end-of-delivery” indication is to use a two-part drive member in which the two parts move together until at or near to the end of travel of the drive member, whereupon the two parts are free to move relative to one another under the action of a stored energy source to create an audible signal. It is advantageous to use the same energy source as is used to drive the drive member through the drug container. However, it should be clear that there are several options for the mechanism for locking and releasing the two parts of the drive member, which in the embodiment of  FIGS. 8 and 9  is realised using the third drive member. For example, features within the powerpack housing might be provided to force the first drive element to rotate relative to the second drive element when the first drive element reaches a particular position within the powerpack housing. 
         [0214]    A skin sensor assembly is provided forward of the drug container, which covers the needle both before and after use and which allows the autoinjector to be activated simply by removing a cap and pressing the autoinjector against an injection site. 
         [0215]    The skin sensor assembly comprises a skin sensor element  112 , shown in  FIG. 10 , and skin sensor spring  114  that is held between the skin sensor element and the chassis. This can be seen clearly in  FIG. 3 . In operation, the skin sensor element interacts with the chassis  120  shown in  FIG. 11  and the lower housing  140  shown in  FIG. 12 . 
         [0216]      FIG. 11  is a perspective view of the chassis  120 . The chassis is formed from a transparent plastic material and includes two window portions  120 , which align with the windows  22  formed in the outer housing  20 . The lower housing  140  clips to the chassis around the window portion  130 , as shown in  FIG. 13 a   . Latches  122  are formed so that they can be flexed outward, out of engagement with the drug container  10 . The chassis has a front end  132  of reduced diameter, which prevents the drug container from travelling beyond an insertion position. A bearing surface  133  is provided against which the skin sensor spring  114  sits. 
         [0217]    The chassis  120  also includes flexible arms  121  formed below the window portions  130 . The flexible arms  121  each comprise a bulb  123  at their free end that abuts a rear end of the skin sensor element  112 . The bulb  123  (in combination with the cap and/or upper housing) prevents the skin sensor element being moved rearward to a position in which the latches  122  can release the drug container  10 , as described with reference to  FIG. 15 . 
         [0218]    The chassis also includes latching elements  124 . Each latching elements  124  comprises a flexible arm  125  extending from the body of the chassis towards a front end of the device, and a hook  126  and cam head  128  on the end of the flexible arm. The hook  126  is configured to engage the skin sensor element  112 . The cam head  128  is positioned inward of the hook and is configured to engage the powerpack housing  64 . Inward in this context is relative to the outer housing. The latching elements  124  on the chassis do not extend inwardly of the surrounding portion of the chassis in order to engage the powerpack or skin sensor element. This is advantageous from a moulding perspective. 
         [0219]      FIG. 12  is a perspective view of the lower housing  140 . The lower housing is secured to the chassis by the clipping of portion  146  around window portion  130  of the chassis. The lower housing  140  includes a pair of second latching elements  144  that, in the initial position are received in openings  115  of the skin sensor element  112 . The lower housing includes recesses  142  for engagement with the cap  30 . Surface  145  acts to limit movement of the skin sensor beyond a fully extended position, as will be described. The lower housing also includes slots  141 , into which flexible arms  121  of the chassis are received. Lugs  148  on the lower housing engage recesses  24  formed in the outer housing. 
         [0220]    In an initial position, prior to use, and as shown in  FIGS. 2 and 3 , the skin sensor element  112  is urged away from the chassis by the skin sensor spring  114 . It is retained to the chassis by engagement of surfaces  116  with latching elements  124 . The second latching elements  144  on the lower housing, in the initial position, are received in openings  115  of the skin sensor element  112 . 
         [0221]      FIGS. 13 a -13 d    show the sequence of operation of the skin sensor assembly, and are side views of the device with the outer housing and cap removed.  FIG. 13 a    shows the device with the cap removed but prior to use. The skin sensor element  112  is retained against the action of the skin sensor spring by the latching element  124 . Specifically hook  126  on the latching element  124  engages surface  114  on the skin sensor element. 
         [0222]      FIG. 13 b    shows the skin sensor element  112  pushed back, as it would be if the skin sensor element were pressed against an injection site. In this position, the hook  126  is clear of the surface  116 . The second latching elements  144  are still received in opening  115  of the skin sensor element. However, the wider portions of opening  115  are now aligned with the position of latches  122  on the chassis. In the position shown in  FIG. 13 b   , the latches  122  no longer retain the drug container  10 , as they can be pushed outwards into the opening  115  in the skin sensor element. Accordingly, the drug container is free to move forward and the insertion spring  61  expands to move the powerpack assembly and drug container to an insertion position, as shown in  FIG. 13   c.    
         [0223]    In  FIG. 13 c    the drug container is in an insertion position, and needle  12  is clearly extending beyond the skin sensor element  112 . In this position, the powerpack assembly has moved forward so that protrusions  63  on the powerpack housing  64 , only an upper end of which can be seen in  FIG. 2 , have pushed against cam head  128  and so have deformed arm  124 . The deformation of arm  124  moves the hook  126  out of the path of surface  116  when it moves forward. 
         [0224]    When the device is removed from the injection site, the skin sensor spring urges the skin sensor element forward. As the arm is deformed, the surface  116  can move past hook  126 . The skin sensor element can then move to a fully extended position as shown in  FIG. 13 d   . In this position the skin sensor element covers the needle again. The skin sensor element is retained to the chassis and prevented from further forward movement by the surface  117  on the skin sensor element abutting the surface  145  on the lower housing. The second latching elements  144  engage with aperture  118  in the skin sensor element  112  to prevent the skin sensor element from being moved back against the skin sensor spring. The second latching elements can ride over sloped surface  119  on the skin sensor element as it moves to its fully extended position to snap into the aperture  118 , whereupon the skin sensor element is locked in a fully extended position. 
         [0225]    The latching mechanism for the skin sensor and for retaining and releasing the drug container is all positioned on two opposite sides of the device. This allows the window  22  to remain unobscured throughout operation of the device. This allows the drug to be easily inspected before use and for the progress of the drug delivery to be observed through the window  22 . 
         [0226]    The device shown in  FIGS. 1 to 13  includes a mechanism to prevent activation prior to removal of the cap.  FIG. 14  is a perspective view of the cap  30 . The cap is formed from a moulded plastics material and comprises protrusions  34  that are configured to engage recesses  142  on the lower body, as shown in  FIG. 2 . The upstanding central tube comprises the hooks  32  shown in  FIG. 2 , for retaining the needle shield. The cap also includes tongues  36  that extend within a space between the outer housing and the chassis when the cap is fitted to the device, as shown in  FIG. 3 . 
         [0227]      FIG. 15  is a detail view of the front end of the device as shown in  FIG. 3 . It can be seen that the tongues  36  on the cap are adjacent flexible arms  121  formed on the chassis, and shown more clearly in  FIG. 11 . The flexible arms  121  comprise a bulb  123  that abuts a rear end of the skin sensor element  112 . The bulb  123  prevents the skin sensor element being moved rearward to a position in which the latches  122  can release the drug container  10 . So, when the cap is engaged to the lower housing  140 , the device cannot be activated. 
         [0228]    When the cap is removed, the arms  121  can be pushed outwardly by the skin sensor element into the space vacated by the tongues  36 , as it the skin sensor is moved rearward. The skin sensor element and bulbs  123  are shaped to allow this to happen smoothly. The lower housing includes apertures  141  into which the arms  123  can deflect. 
         [0229]      FIGS. 16 a  to 16 g    illustrate the sequence of operation of the device of the first embodiment.  FIGS. 16 a  to 16 g    are cross-section views, similar to  FIG. 2 , but with the cap removed.  FIG. 16 a    shows the device immediately after cap removal, but prior to the pressing of the skin sensor element against an injection site. It can be seen that the needle shield assembly has been removed together with the cap. 
         [0230]      FIG. 16 b    shows the device with the skin sensor element pushed back. Second latching elements  144  on the lower housing prevent the skin sensor from moving further back. In this position, the latches  122  on the chassis are free to bend out into the windows  115 , but have not yet done so. 
         [0231]      FIG. 16 c    shows the drug container  10  and powerpack housing  64  moved to an insertion position by the expansion of insertion spring  61 . In this position, the needle  12  is inserted into the injection site. The second drive element  80  is just clear of the shaft portion  108  of the retaining means  100 . This means that legs  87  can be squeezed together to disengage from the lugs  86  from surface  69  on the powerpack housing  64 . The protrusions  63  on the powerpack housing has deflected the latching arms  124  so that the skin sensor element  112  is free to move forward to a fully extended position once it is removed from the injection site. 
         [0232]      FIG. 16 d    shows the drive member disengaged from the powerpack housing and at the point of first contact of the drive member with the sealing foil. The drive spring is expanding to urge the drive member forward. 
         [0233]      FIG. 16 e    shows the drive spring further expanded and the drive member further forward. The foil has been ruptured and the plunger has been moved through the drug container and almost all the drug has been ejected. At this point, the third drive element has engaged the rear end of the drug container and so moved back relative to the second drive element. In this position, the drive element is no longer engaged to the second drive element, and the second drive element is able to rotate relative to the first drive element, as described with reference to  FIGS. 8 and 9 . 
         [0234]      FIG. 16 f    shows the first drive element driven forward onto the second drive element, with the second drive element rotated, to provide an audible indication of the end of drug delivery. The plunger is in a fully forward position, with the intended volume of drug ejected. At this point, the user can remove the device from the injection site. 
         [0235]      FIG. 16 g    shows the device after it has been removed from the injection site, with the skin sensor element in a fully extended position, locked and covering the needle. As described with reference to  FIG. 13 d   , the skin sensor element is retained to the chassis and prevented from further forward movement by surface  117  on the skin sensor element abutting the surface  145  on the lower housing. The second latching elements  144  engage with aperture  118  in the skin sensor element  112  to prevent the skin sensor element from being moved back against the skin sensor spring. 
         [0236]    It can be seen from  FIG. 2  and  FIGS. 16 a - c   , that the drive member  70  and all of the other components of the device are held apart from the sealing foil  16  until the time at which the sealing foil is ruptured. Prior to use, the drive member  70  is held a predetermined distance from the sealing foil  16 . The powerpack housing  64  is fixed to the sides of the drug container and does not contact the sealing foil. During the needle insertion stage of operation, the sealing foil  16  remains untouched. This arrangement ensures that the sealing foil can be tested before the drug container is assembled to the rest of the autoinjector, and the sealing foil then remains untouched until the point of drug delivery. This reduces the possibility of contamination or loss of drug before delivery. 
         [0237]      FIG. 17  is a schematic diagram illustrating the sequence of assembly of an autoinjector of the first embodiment. In step  150 , the drug container assembly  10 , including the needle  12  and needle shield  50  is filled with dose of drug and a plunger  14 , and then sealed by a sealing foil  16 . This is carried out in a sterile environment. Independently, in step  152 , the powerpack assembly is assembled, with the retaining means holding the drive and insertion springs in a compressed state. In step  154  the filled drug container assembly in then fitted to the powerpack assembly, the lower powerpack housing clipping to the drug container  10 . In step  156 , the front end of the device, including the chassis, skin sensor element, skin sensor spring, and lower housing are assembled. The cap is typically coupled to the front end assembly at this stage, but this is shown as a separate step  157 . In step  158  the front end assembly is coupled to the drug container assembly and powerpack assembly. The drug container assembly is retained by latching arms on the chassis. In step  160 , the outer housing is placed over the powerpack assembly and engages with the lower housing  140 . The cam surfaces  25  on the outer housing  20  engage the retaining means  100  and force the retaining means to rotate out of engagement with the powerpack housing  64  just before the lugs  148  on the lower housing engage recesses  24  formed in the outer housing. The insertion spring  61  is allowed to expand a small amount as the powerpack housing disengages from the retaining means, but it is held in a second compressed state by the action of latches  122  on the chassis engaging the drug container  10 . In the second compressed state, the insertion spring still stores enough energy to insert the needle  12  into an injection site by pushing the drug container to the insertion position. 
         [0238]    The cap  30  is typically assembled to the lower housing  140  during assembly of the front end assembly, but may be added after the powerpack and front assembly are joined or after the outer housing has been fitted to the lower housing. These options are illustrated in  FIG. 17  as step  157 . 
         [0239]    The autoinjector is fully assembled and ready for use at step  162 . This production sequence has the advantage that the powerpack assembly can be produced independently of the other components and transported and stored separately. Steps  156 ,  157 , 158  and  160  are very simple and easily automated. 
         [0240]    The first described embodiment also has the advantage that different length and shaped outer housing can be used for different drugs with the same powerpack assembly. The features  25  used to rotate the retaining means out of engagement with the powerpack housing  64  do not need to be manufactured with the same tight tolerances on dimensions that the shaft portion  108  of the retaining means requires. It is therefore a simple matter to provide different outer housings to provide a distinctive appearance for devices for particular drugs or for devices associated with particular brands. Users can then quickly recognise if they have the appropriate device. Different outer housing may also be provided to suit different user groups that may have different specific requirements e.g. they may have limited manual dexterity. 
         [0241]      FIG. 18  is a perspective view of an autoinjector  201  in accordance with a second embodiment of the invention, before use. The autoinjector  201  comprises an outer housing  220 , having a viewing window  222  through which a drug within the autoinjector can be inspected. A cap  230  is provided to cover the needle insertion end of the device and to prevent inadvertent activation of the device. The autoinjector is compact, being approximately 10 cm long and fits easily in a user&#39;s hand. 
         [0242]      FIG. 19  is a cross-sectional view through the autoinjector  201  of  FIG. 19 .  FIG. 20  is a second cross-sectional view through the autoinjector of  FIG. 19 , at 90 degrees to the cross-section of  FIG. 19 . 
         [0243]    The autoinjector  201  shown in  FIGS. 18, 19 and 20  comprises a drug container assembly (shown in  FIG. 21 ), a powerpack assembly including a powerpack housing  264  (as shown in  FIG. 27 ), a drive member  270  and insertion and drive springs  260 ,  262 , an internal housing (shown in  FIG. 23 ), herein referred to as the chassis, a skin sensor assembly comprising a skin sensor element (shown in  FIG. 22 ) and a skin sensor spring, a lower housing (shown in  FIG. 26 ), an outer housing and a cap (shown in  FIG. 25 ). 
         [0244]    The drug container assembly  210  is held within the chassis  320  and in operation moves through the chassis. The drug container assembly  210  is retained in an initial position by latches  322  on the chassis, which engage protrusions  213  on the cradle  215  that surrounds the drug container  211 . The latches  322  are prevented from releasing the cradle by the skin sensor assembly. The skin sensor assembly comprises a skin sensor element  312  and a skin sensor spring  314 . The skin sensor element is held by latching elements  324  on the chassis  320  and urged away from the drug container assembly  210  by the skin sensor spring  314 , which is held between the chassis  320  and the skin sensor element  312 . The lower housing  340  engages the chassis  320  by clipping to a T-shaped protrusion  328  on the chassis. Window portions  348  on the lower housing engage window  222  formed in the outer housing. The cap  230  engages the channel  342  on the lower housing and covers the skin sensor element  312 . 
         [0245]      FIG. 21  is a perspective view of the drug container assembly shown in  FIGS. 19 and 20 . The drug container assembly comprises a drug container  211  and cradle element in which the drug container  211  is held. The cradle and drug container may be formed as separate components or may be co-moulded together. The drug container  211  contains a drug to be delivered to a patient by injection, with a hypodermic needle  212  fixed to a front end. As in the first embodiment, the drug container is formed from cyclic olefin, which has excellent drug contact properties. The cradle may be formed of a different material and advantageously is formed from a mouldable plastic. Clipping features  213  and  219  are formed on the cradle  215 . 
         [0246]    A plunger  214  is provided within the drug container. Movement of the plunger  214  within the drug container  211  urges the drug out through the needle  212 . The plunger is of the same type as described with reference to the first embodiment and is designed to provide low friction with the walls of the drug container and to minimise any stiction between the plunger and the drug container. The internal surface of the front end of the drug container  211  is again shaped to match the shape of the front end of the plunger  214  to maximise the amount of drug that is pushed out of the drug container during use. 
         [0247]    A sealing foil  216  is provided at a back end of the drug container  211  to ensure the drug is retained and maintained in a sterile and pristine condition. The sealing foil  216  may be laminated foil including a layer of aluminium and may be welded to a back end of the drug container  211 . 
         [0248]    As in the first embodiment, the hypodermic needle  212  is glued into a needle hub portion  217  of the drug container  211 . However, the drug container may be moulded around the needle. The needle is covered by a needle shield  250  that keeps the needle  212  sterile. As described in the first embodiment, the needle shield  250  comprises a rigid outer housing  252  that forms a seal with the needle hub portion  217 . An elastomeric plug  254  is provided within the needle shield into which the front end of the needle  212  is inserted. The elastomeric plug seals the needle and ensures that no drug can escape from the needle prior to removal of the needle shield. The rigid outer housing  252  of the needle shield may be transparent to allow for inspection of the needle during assembly of the autoinjector. The front end of the needle shield outer housing  252  comprises a bulb  256  to engage hooks  232  in the cap  230 , as shown in  FIG. 19 . This ensures that when the cap  230  is removed the needle shield is removed with it. 
         [0249]    The sealing of the needle shield to the needle hub is achieved using an interference fit in the same manner as described for the first embodiment and shown in  FIG. 5 . 
         [0250]    As in the first embodiment, the autoinjector shown in  FIGS. 18 to 20  comprises an automatic mechanism for inserting the needle into an injection site and for ejecting the drug through the needle into the injection site. The automatic mechanism is referred to herein as the powerpack assembly. The powerpack assembly comprises stored energy sources, in the form of compressed springs  260 ,  262 . When the first spring  260 , referred to as the insertion spring, is released it moves the drug container assembly  210  through the housing of the autoinjector to insert the needle  212  into an injection site. The second spring  262 , referred to as the delivery spring, is then released to move the plunger  214  through the drug container  211  to inject the drug. The springs  260 ,  262  and the mechanism for controlling a sequence of release of the springs within the powerpack assembly are positioned rearward of the drug container assembly. 
         [0251]    The powerpack comprises a powerpack housing  264 , shown in  FIG. 22 , that is coupled to the drug container assembly  210 . The powerpack housing  264  has arms  265  that clip to the features  219  on the cradle  215 . The insertion spring  260 , shown in  FIGS. 19 and 20  in a compressed condition prior to use of the autoinjector, is positioned between the powerpack housing  264  and the outer housing  220 . When the drug container assembly is released from the latches  322  on the chassis, the drug container assembly is free to move forward through the chassis to an insertion position, pushed by the expansion of the insertion spring  260 , as will be described. 
         [0252]    The drive spring  262  is positioned between the powerpack housing  264  and a drive member  270 . In an initial position, the drive spring is prevented from expanding by the engagement of protrusions  272  on the drive member  270  with surface  267  on the powerpack housing. 
         [0253]    The drive member  270  comprises a front end surface  276  that has a serrations to aid rupture of the sealing foil  216  and which in use engages with the plunger, as will be described. The drive member  270  also has resilient legs  274  that are pressed outwardly by a locking surface  226  that is part of (or rigidly fixed to) the main housing  20  so that protrusions  272  engage with the powerpack housing and are prevented from disengagement with the locking surface  226 . In this way the drive spring  262  is locked in a compressed state, and moves with the powerpack housing  264 , until the protrusions  272  can be released from the surface  267 . 
         [0254]    When the powerpack housing has travelled to an insertion position, the drive member has travelled beyond the locking surface  226 . At this point, because the locking surface is no longer between the legs  274 , the legs  274  can be squeezed together allowing the drive member to disengage from the surface  267  on the powerpack housing. The drive member can then be moved forward by the drive spring  262  to rupture the sealing foil  216  and push the plunger  214  through the drug container  211  to dispense the drug through the needle  212 . 
         [0255]    As in the first embodiment, in the second embodiment a skin sensor assembly is provided forward of the drug container, which covers the needle both before and after use and which allows the autoinjector to be activated simply by removing a cap and pressing the autoinjector against an injection site. 
         [0256]    The skin sensor assembly comprises a skin sensor element  312  and a skin sensor spring  314 . The skin sensor spring  314  is held between the skin sensor element and the chassis. This can be seen clearly in  FIG. 19 . In operation, the skin sensor element interacts with the chassis  320 . 
         [0257]      FIG. 23  is a perspective view of the skin sensor element of the second embodiment. The skin sensor element comprises a front surface  313  which contacts the injection site in use, and which has an aperture through which the needle passes during insertion of the needle. Apertures  315  are provided so that when the skin senor element is in a retracted position they align with the latches  322  on the chassis, allowing the latches to deflect outwardly out of engagement with features  213 , releasing the drug container. Hooks  316  are provided to engage the chassis in an initial position, retaining the skin sensor element against the force applied by the skin sensor spring. Surfaces  317  are provided to abut the chassis and prevent retraction of the chassis when the skin sensor element is in a fully extended position. Bracing arms  318  provide mechanical rigidity. 
         [0258]      FIG. 24  is a perspective view of a chassis of the second embodiment. The chassis is formed from a plastics material. The chassis is again essential tubular with a central bore through which the drug container assembly can move axially. The chassis has a front end  332  of reduced diameter beyond which the drug container assembly cannot travel. At the front end, the chassis includes a pair of cantilever arms  334  extending radially inward. The drug container assembly contacts and deflects the cantilever arms in the insertion direction, also referred to as the axial direction herein, as it moves to an insertion position. The deflection of the cantilever arms decelerates the drug container assembly as it reaches the insertion position, reducing force applied to the injection site through the skin sensor spring and skin sensor from the chassis. The cantilever arms  334  are constructed to extend rearward from their fixed end to their free end so that they can deflect before being level with the rest of the front end of the chassis. 
         [0259]    The chassis comprises latching elements  324  that engage hooks  316  on the skin sensor element. The latching elements  324  are resilient arms that extend rearward from their fixed and but at an angle offset from the axial direction. The latching elements can be deflected by camming features  269  on the powerpack assembly to allow the hooks  316  to pass as the skin sensor moves to an extended position. The chassis comprises locking arms  326 , which are resilient arms that extend forward from their fixed end. The locking arms can flex to allow the skin sensor element to pass when the skin sensor moves from a retracted position to an extended position, but are configured to prevent the surfaces  317  from passing back over the locking arms  326  once the skin senor has reached the fully extended position. 
         [0260]      FIGS. 25 a -25 c    show the sequence of operation of the skin sensor assembly, and are side views of the device with the outer housing and cap removed.  FIG. 25 a    shows the device prior to use. The skin sensor element  312  is retained against the action of the skin sensor spring by the latching element  324 . Specifically hook  316  on the skin sensor element engages the latching element  324 . 
         [0261]      FIG. 25 b    shows the skin sensor element  312  pushed back, as it would be if the skin sensor element were pressed against an injection site, and the powerpack moved forward. In this position, the hook  316  is clear of the surface latching element  324 . The apertures  315  are now aligned with the position of latches  322  on the chassis. In the position shown in  FIG. 25 b   , the latches  322  no longer retain the drug container assembly  210 , as they can be pushed outwards into the apertures  315  in the skin sensor element. Accordingly, the drug container  311  has moved forward and the insertion spring  261  expanded to move the powerpack assembly and drug container to an insertion position. 
         [0262]    As the powerpack assembly moves forward to the insertion position, camming ridge  269  engages the latching elements  324  to deflect the latching elements so that they extend in an axial direction, as shown. 
         [0263]    When the device is removed from the injection site, the skin sensor spring  314  urges the skin sensor element  312  forward. As the latching arms  324  are deflected, the hooks  316  can pass the latching elements  324  as the skin sensor element moves forward. The skin sensor element  312  can then move to a fully extended position as shown in  FIG. 25 c   . In this position, the skin sensor element covers the needle again. The skin sensor element is retained to the chassis and prevented from further forward movement by the engagement of bracing arms  318  with a portion of the lower housing  340  (not shown in  FIG. 25 c   ). The locking arms  326  flex to allow the skin sensor element to pass when the skin sensor moves from a retracted position to an extended position, but surfaces  317  then engage the locking arms  326  if the skin sensor element is pushed back towards a retracted position, locking the skin sensor element in the extended position. 
         [0264]      FIG. 26  is a perspective view of the lower housing of the second embodiment. The lower housing  340  is formed from a transparent plastics material and includes window portions  348 . The lower housing fits over the skin sensor and chassis but partially within the outer housing. Window portions  348  have raised outer rims that and engage windows  222  formed in the outer housing. The lower housing  340  engages the chassis  320  by apertures  344  receiving T-shaped protrusions  328  on the chassis. Channel  342  on the lower housing is provided to engage the cap  330 . 
         [0265]      FIG. 27  is a perspective of the cap of the second embodiment. The cap  230  comprises a central cylindrical tube portion comprising three angularly spaced, inwardly projecting hooks  232 , shown in  FIG. 19 , that can be pushed over and engage the bulb  256  on the needle shield  250 . This ensures that the needle shield is removed with the cap when the device is to be used. The cap also comprises three inwardly projecting lugs  234 , equally spaced around the circumference on the cap, that are configured to engage the lower housing  340 . To remove the cap, a user simply grips and squeezes the cap between two fingers and pulls the cap away from the lower housing. The use of three, equally spaced lugs ensures that when the cap is radially squeezed by a user, at least two of the lugs will move outwardly to disengage from the lower housing, whatever direction the cap is squeezed in. This ensures that the cap can be easily removed. 
         [0266]      FIGS. 28 a  to 28 e    are cross-section views of the second embodiment, illustrating the sequence of operation.  FIG. 28 a    shows the device immediately after cap removal, but prior to the pressing of the skin sensor element against an injection site. It can be seen that the needle shield assembly has been removed together with the cap. 
         [0267]      FIG. 28 b    shows the device with the skin sensor  312  element pushed back, compressing the skin sensor spring  314 . The bracing arms  318  on the skin sensor element abut the chassis to prevent the skin senor element from moving further back. In this position, the latches  322  on the chassis are free to bend out into the windows  315 . 
         [0268]      FIG. 28 c    shows the drug container  211  and powerpack housing  264  moved to an insertion position by the expansion of insertion spring  261 . In this position, the needle  212  is inserted into the injection site. The drive member  270  is just clear of the locking surface  226  on the outer housing. This means that legs  274  can be squeezed together to disengage the lugs  272  from surface  267  on the powerpack housing  264 . The drive spring  262  is free to expand. The camming protrusions  269  on the powerpack housing have deflected the latching elements  324  so that the skin sensor element  312  is free to move forward to a fully extended position once it is removed from the injection site. 
         [0269]      FIG. 28 d    shows the drive spring  262  expanded. The sealing foil  216  has been ruptured and the plunger  214  has been moved through the drug container and the drug has been ejected. 
         [0270]      FIG. 28 e    shows the device after it has been removed from the injection site, with the skin sensor element in a fully extended position, locked and covering the needle. The skin sensor element is retained to the chassis and prevented from further forward movement by the engagement of bracing arms  318  with a portion of the lower housing  340 . The locking arms  316  have flexed to allow the skin sensor element to pass as the skin sensor to the extended position, but surfaces  317  lock the skin sensor element in the extended position, preventing any retraction of the skin sensor element. 
         [0271]      FIG. 29  is a schematic diagram illustrating the assembly process of an autoinjector in accordance with the second embodiment of the invention. In step  350 , the drug container assembly  210 , including the needle  212  and needle shield  250  is filled with dose of drug and a plunger  214 , and then sealed by a sealing foil  216 . This is carried out in a sterile environment. Independently, in step  352  the powerpack assembly is assembled to the outer housing. In step  354  the filled drug container assembly is then fitted to the powerpack assembly. The front end of the device, including the chassis, skin sensor element, skin sensor spring, and lower housing is assembled in step  356 . The powerpack housing includes locking arms  266 , which are received in openings  224  in the outer housing to retain the insertion spring in a first compressed state. The locking surface  226  engages the drive member  270  to hold the drive spring in a compressed state. 
         [0272]    In step  358 , the front end assembly is coupled to the drug container assembly and the powerpack assembly and outer housing. The drug container assembly is retained by latching arms on the chassis. The window portions  348  of the lower housing clip into to the windows  222  of the outer housing. As the lower housing is moving towards an engaged position in which the window portions are fully engaged with the windows on the outer housing, the chassis  320  engages the arms  266  on the powerpack housing to move them out of the openings  224 . This mechanism is illustrated in  FIG. 30 . 
         [0273]    The chassis includes cam surfaces  336  at its rear end that engage corresponding cam surfaces  267  on the locking arms  266 . As the chassis and powerpack move toward one other, the cam surfaces  267  on the chassis deflect locking arms inwardly and out of engagement with the outer housing  220 . At this point, the insertion spring  260  is allowed to expand a small amount, but it is subsequently held in a second compressed state as soon as the lower housing  340  engages the outer housing. The latches  322  on the chassis engage the drug container assembly  210 , the chassis  320  is fixed to the lower housing and the lower housing is fixed to the outer housing. Accordingly, the insertion spring cannot expand until the latches  322  are released from the drug container. In the second compressed state, the insertion spring still stores enough energy to insert the needle  12  into an injection site by pushing the drug container to the insertion position when the latches  322  are released. The components are configured so that the disengagement of the locking arms  266  from the outer housing happens only momentarily before the window portions  348  lock to the window  222   
         [0274]    The cap  30  is typically assembled to the lower housing  340  during assembly of the front end assembly, but may be added after the powerpack and front assembly are joined or after the outer housing has been fitted to the lower housing. These options are illustrated in  FIG. 29  as step  357 . Also, as an alternative to the process illustrated in  FIG. 29 , the drug container assembly could be assembled to the front end assembly before being coupled to the powerpack and outer housing. The assembly process is complete at step  360 .