Patent Publication Number: US-11033689-B2

Title: Plunger-driven auto-injectors

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional of U.S. application Ser. No. 14/258,569, filed Apr. 22, 2014, which claims the benefit of U.S. Provisional Application No. 61/817,981, filed on May 1, 2013, which is included by reference herein in its entirety for all purposes. 
    
    
     FIELD 
     THIS INVENTION relates to automatic injectors for retractable syringes. More particularly, this invention relates to plunger sub-assemblies for automatic injectors and automatic injectors for retractable syringes having low retraction activation force, the methods of operating such devices, and the methods of assembling such devices. 
     BACKGROUND 
     Manually activated syringes are commercially available from a variety of manufacturers, including the owner and assignee of the present invention, and are used in the administration of drug solutions, drug suspensions, vaccines, medicinal therapies, and any other liquid medicament by parenteral injection. Such syringes are commonly utilized by medical practitioners to administer injections to patients but are difficult to use by self-administering patients. 
     An auto-injector is an automatic injection device designed to facilitate delivery of a dose of medicament to a patient through a hypodermic needle, the injection usually being administered by the patient themselves. An auto-injector works, for example, by delivering an injection automatically upon activation by the patient. This is in contrast to a conventional manually activated syringe where the patient themselves needs to directly depress a plunger into a barrel containing medicament in order to effect the injection. Auto-injectors have proven particularly useful in allowing the medically untrained user to administer a parenteral injection, and can provide both psychological and physical advantages to patients. Patients needing to inject medication for chronic disease management have used auto-injectors since the first reusable auto injector was introduced in the 1990s. An auto injector provides protection for the primary container, generally a pre-filled syringe, and offers an easy-to-use solution for automatic injection of medication. As used herein, the terms “automatic injector” and “auto-injector” are meant to refer to the same devices. 
     In addition to automatic needle insertion and dose delivery, some auto-injectors also incorporate safety mechanisms to automatically protect the patient from the needle after use. The automatic injectors of the prior art are usually provided with needle shields which extend over the needle when actuated. However, such safety mechanisms may fail to actuate and/or can be easily reversed, thereby leaving the patient exposed to the needle and susceptible to injury. Additionally, known automatic injectors generally link visual, tactile or audible indicators to the end of plunger stroke or actuation of some safety mechanism, instead of to the end of drug dose. Accordingly, the self-administering patient is not provided with an indication that the drug has been fully delivered and may remove the needle or actuate the safety mechanisms prematurely. 
     SUMMARY 
     The present invention provides plunger sub-assemblies for automatic injectors and automatic injectors for retractable syringes having low retraction activation force, the methods of operating such devices, and the methods of assembling such devices. The automatic injectors of the present invention provide integrated safety features which automatically retract the needle or cannula into the device to, for example, prevent injuries related to accidental needlestick. Additionally, the embodiments of the present invention provide true end of dose indication to users, informing the user that the drug delivery has completed and that the device is safe for removal and disposal. Furthermore, the embodiments of the present invention provide plunger sub-assemblies which reduce forces required to activate retraction of the needle or cannula, thereby providing significant manufacturing, assembly, and operational benefits. As such, the present invention provides plunger-driven automatic injectors for use for the efficient and safe delivery of drugs or therapeutics to patients. Accordingly, the novel devices of the present invention alleviate one or more of the problems associated with prior art devices, such as those referred to above. 
     In one broad form, the present invention provides a plunger sub-assembly for an automatic injector, the plunger sub-assembly comprising a plunger inner and plunger outer that maintain a retraction biasing member in an initially energized state. 
     In an aspect of this broad form, the plunger sub-assembly comprises a plunger outer having one or more engagement prongs, a plunger inner having one or more engagement slots and a retraction biasing member, whereby the one or more engagement prongs and the one or more engagement slots are capable of releasable engagement to retain the retraction biasing member in an initially energized state between the plunger outer and the plunger inner. 
     In at least one embodiment, the plunger outer has two engagement prongs for releasable engagement with the engagement slot(s) of the plunger inner. The retraction biasing member, which may be a spring such as a compression spring, is retained in a first energized state between the plunger outer and plunger inner when the engagement prongs of the plunger outer are releasably engaged with the engagement slots of the plunger inner. In at least one embodiment, the retraction biasing member is a compression spring. The retraction spring may be held in the first energized state between a ledge of the plunger inner and a base of the plunger outer. The one or more engagement prongs are capable of flexing substantially radially to release from engagement with the engagement slots of the plunger inner to permit the retraction spring to expand from the first energized state to a second expanded state. In at least one embodiment, the plunger inner has a seal-engaging member to engage a complementary engagement recess of a plunger seal. The seal-engaging member may be, for example, a screw-threaded aspect that is capable of screwing into the engagement recess of the plunger seal. 
     In another broad form, the present invention provides an automatic injector having a plunger sub-assembly, wherein the automatic injector comprises a housing, an activation mechanism, and a plunger sub-assembly at least partially mounted within a syringe cartridge having a needle assembly. 
     In at least one aspect of this broad form, the automatic injector comprises a housing, a syringe cartridge, a needle assembly comprising a retractable needle and the plunger assembly of the aforementioned aspect at least partially mounted within the syringe cartridge, and an activation mechanism operable to facilitate sequential depression of the plunger assembly to deliver fluid contents of the syringe cartridge and subsequent retraction of the plunger inner when engaged with the retractable needle. 
     The automatic injector may further comprise an injection biasing member residing in an initial energized state substantially within the plunger inner. As previously described, in at least one embodiment, the plunger sub-assembly includes a plunger outer having one or more engagement prongs, a plunger inner having one or more engagement slots which correspond with or engage the engagement prongs of the plunger outer, and a retraction biasing member retained in a first energized state between said plunger outer and plunger inner when the engagement prongs of the plunger outer are releasably engaged with the engagement slots of the plunger inner. The injection biasing member suitably resides within the plunger inner and is held in an initial energized state between a locking plateau of the housing and a platform of the plunger inner. The injection biasing member and the retraction biasing member may be respective compression springs in at least one embodiment of the present invention. 
     The plunger sub-assembly preferably has one or more locking hooks at a proximal end of the plunger inner which initially engage a locking plateau. In a particular embodiment, the one or more locking hooks may initially directly engage the locking plateau at an interior proximal end of the housing. In at least one embodiment, the activation mechanism is capable of directly engaging or contacting the one or more locking hooks of the plunger sub-assembly to disengage the locking hooks from the locking plateau of the housing. The housing may further include one or more recesses on the inner surface of the housing wherein, when the one or more engagement prongs interface with the recesses, the substantially radial flexion of the engagement prongs into the recesses permits the engagement prongs to disengage from the engagement slots of the plunger inner. This disengagement permits the retraction biasing member to be released from the first energized state to a second expanded state for retraction of the needle assembly. In the specific context of a compression spring, this comprises expansion of the compression spring. Accordingly, little or no additional force is needed to disengage the plunger outer from the plunger inner beyond the force utilized to axially translate the plunger sub-assembly to the portion of the housing where the engagement prongs may radially flex into the recesses. 
     Accordingly, by user action on the activation mechanism, the activation mechanism engages or contacts the one or more locking hooks of the plunger sub-assembly to disengage the locking hooks from the locking plateau of the housing. This action permits the actuation spring to expand, thereby translating the plunger sub-assembly within the housing in the distal direction substantially along the axis of the automatic injector. As the engagement prongs of the plunger sub-assembly reach recesses within the inner surface of the housing, the one or more engagement prongs of the plunger outer are permitted to flex substantially radially to disengage from the corresponding engagement slots of the plunger inner. This action permits the retraction spring to expand, thereby translating the plunger inner in the proximal direction substantially along the axis of the automatic injector for retraction of the needle assembly. If the syringe cartridge contains a drug treatment, such as in the case of a pre-filled syringe, the function of the plunger sub-assembly may be utilized to insert a needle and deliver the drug treatment into a patient. Optionally, when a retractable syringe is utilized as a syringe cartridge, the actuation mechanism may further be utilized to activate a retraction mechanism. 
     In a preferred embodiment of the present invention, the syringe cartridge of the automatic injector is a retractable syringe. Such syringes may further contain safety features which retract the needle after use, providing desirable needle-stick prevention, and prevent re-use of the syringe. Suitably, the plunger sub-assembly is slidably moveable within the barrel of the syringe to thereby facilitate delivery of the drug treatment to a user, patient or other recipient. The retractable syringe may include a retractable needle assembly. Preferably, the plunger sub-assembly is capable of engaging or contacting the needle assembly, or a portion thereof, to cause retraction of the cannula or needle. Suitably, retraction of the needle is facilitated by a biasing member such as a spring, elastic or other member capable of storing and releasing energy to facilitate needle retraction. It will be appreciated that the retractable syringe may comprise any needle retraction mechanism that is operable with the automatic injector disclosed herein. By way of example, the needle retraction mechanism may be as described in one or more of the following, although without limitation thereto: U.S. Pat. Nos. 6,083,199, 7,500,967, 7,935,087, 8,021,333, 8,002,745, 8,052,654, 8,114,050, 8,167,937, and 8,361,035; U.S. Patent Pub. No. 2013/0226084; and International PCT App. Nos. PCT/AU2010/001677, PCT/US2012/067793, and PCT/US2014/024781 all of which are incorporated herein by reference, in their entirety, for all purposes. 
     According to one embodiment, the retractable syringe comprises: a needle assembly comprising the retractable needle, wherein the retractable needle comprises a cannula and a needle body. The needle assembly may further comprise a needle seal engageable by the plunger seal mounted to the plunger inner. Preferably, the needle assembly is configured such that the needle seal retains the retractable needle and the cannula of the retractable needle passes through the needle seal to permit delivery of one or more substances and/or mixed substances to a user, patient, or other recipient. In one embodiment, the needle assembly is similar to that disclosed in International PCT App. No. PCT/AU2010/001677 which includes a needle body that is capable of being captured by the plunger seal, such as within a recess within the plunger seal, for retraction into the barrel of the syringe cartridge and/or the housing of the automatic injector. In an alternative embodiment, the needle assembly may be similar to that disclosed in International PCT App. Nos. PCT/US2012/067793 or PCT/US2014/024781, which do not require a needle body and which activate retraction of the cannula generally through contact between the plunger seal and needle seal. 
     In at least one embodiment of the present invention, the automatic injector further includes a sleeve having one or more protrusions that are initially held by a cap in an engaged position within corresponding notches on the interior surface of housing. Upon removal of the cap, protrusions are permitted to flex radially inwards to disengage from the notches. The sleeve is configured to permit axial translation in a distal direction until a bridge portion of sleeve contacts a corresponding depth limiter on the interior surface of the housing. The automatic injector further includes one or more windows within the housing to view the internal components and function of the automatic injector. The windows may be transparent, opaque, or translucent, for example. The automatic injector may also include a tactile biasing member, such as a compression spring, between the activation mechanism and the proximal end of the housing. 
     In yet another broad form, the present invention provides a method of assembling an automatic injector. Suitably, the automatic injector is according to the aforementioned aspect. 
     In an aspect of this broad form, the method includes the steps of: 
     (i) inserting an injection biasing member into a housing and compressing the injection biasing member between the housing and the plunger inner, substantially or at least partially within a chamber of the plunger inner, by releasably engaging the plunger inner with the housing; 
     (ii) assembling a plunger sub-assembly by engaging one or more engagement prongs of a plunger outer one or more engagement slots of a plunger inner so that a retraction biasing member is retained in an initially energized state between said plunger outer and plunger inner; and 
     (iii) inserting the plunger sub-assembly into the housing such that at least a portion of the plunger inner resides within a barrel of a syringe cartridge is permitted to axially translate therein. 
     In a preferred form, the method of assembly includes: (i) inserting an injection biasing member into a housing and compressing the injection biasing member between the housing and the plunger inner, substantially or at least partially within a chamber of the plunger inner, by detachably engaging one or more locking hooks of the plunger inner with a locking plateau of the housing; (ii) assembling a plunger sub-assembly including a plunger outer having one or more engagement prongs, a plunger inner having a corresponding engagement slots, and a retraction biasing member retained in a first energized state between said plunger outer and plunger inner when the engagement prongs of the plunger outer are releasably engaged with the engagement slots of the plunger inner; and (iii) inserting the plunger sub-assembly into the housing such that at least a portion of the plunger inner resides within a barrel of a syringe cartridge is permitted to axially translate therein. The injection biasing member is initially maintained in an energized state substantially within an upper portion of the plunger inner. In another embodiment, the method further includes the step of: attaching an activation mechanism to the housing wherein the activation mechanism is configured to contact the one or more locking hooks of the first actuation pill upon activation. The engagement prongs of the plunger outer are maintained in a releasably engaged configuration with the engagement slots of the plunger inner by a first inner diameter of the housing. The method may further include the steps of: (iv) filling a drug chamber of a syringe cartridge with a drug fluid, and (v) inserting the distal end of the plunger sub-assembly into the proximal end of the syringe cartridge. Steps (iv) and (v) may occur before or after step (iii). 
     Throughout this specification, unless otherwise indicated, “comprise,” “comprises,” and “comprising” are used inclusively rather than exclusively, so that a stated integer or group of integers may include one or more other non-stated integers or groups of integers. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Non-limiting embodiments of the invention are described herein with reference to the following drawings wherein: 
         FIG. 1A  shows an isometric view of an automatic injector, according to one embodiment of the present invention; 
         FIG. 1B  shows an isometric view of the interior components of the automatic injector shown in  FIG. 1A ; 
         FIG. 2  shows an exploded view of an automatic injector, according to one embodiment of the present invention; 
         FIG. 3A  shows an exploded view of a plunger sub-assembly for an automatic injector, according to one embodiment of the present invention; 
         FIG. 3B  shows an enlarged view of the plunger sub-assembly shown in  FIG. 3A  in an energized state; 
         FIG. 3C  shows a cross-sectional view of the plunger sub-assembly shown in  FIG. 3A ; 
         FIG. 3D  shows a 90 degree rotation of the cross-sectional view shown in  FIG. 3C ; 
         FIG. 4  shows a cross-sectional view of another embodiment of the plunger sub-assembly for an automatic injector, in a configuration capable of retracting a needle assembly upon or after completion of drug delivery; 
         FIG. 5  shows an automatic injector including a plunger sub-assembly, according to one embodiment of the present invention, in a locked configuration; 
         FIG. 6  shows an automatic injector including a plunger sub-assembly, according to one embodiment of the present invention, in an unlocked and activated configuration for needle insertion and drug delivery; 
         FIG. 7  shows an automatic injector including a plunger sub-assembly, according to one embodiment of the present invention, in a retraction activated configuration; 
         FIG. 8  shows an automatic injector including a plunger sub-assembly, according to one embodiment of the present invention, in a second expanded state and retraction completed configuration; 
         FIG. 9  shows an embodiment of a needle assembly engaged by a plunger prior to retraction; 
         FIG. 10  shows an enlarged view of the retraction activated configuration shown in  FIG. 7 , in which a plunger outer disengages from a plunger inner to facilitate expansion of the retraction biasing member from its first energized state for needle retraction; and 
         FIG. 11  shows an enlarged view of the second expanded state and retraction completed configuration shown in  FIG. 8 . 
     
    
    
     DETAILED DESCRIPTION 
     The novel devices of the present invention provide integrated safety features which automatically retract a needle or cannula into the device and provide true end of dose indication to users. Additionally, the embodiments of the present invention reduce the forces necessary to activate the needle retraction features of the device, thereby providing operational and manufacturing advantages. Such devices are safe and easy to use, and are aesthetically and ergonomically appealing for self-administering patients. The devices described herein incorporate features which make activation, operation, and lock-out of the device simple for even untrained users. The embodiments of the present invention provide these desirable features without any of the problems associated with known prior art devices. 
     As used herein to describe the actuation mechanisms, plunger sub-assemblies, automatic injectors, syringe cartridges, or any of the relative positions of the components of the present invention, the terms “axial” or “axially” refer generally to a longitudinal axis “A” around which the components of the automatic injectors are preferably positioned, although not necessarily symmetrically there-around. The term “radial” refers generally to a direction normal to axis A. The terms “proximal,” “rear,” “rearward,” “back,” or “backward” refer generally to an axial direction in the direction “P” of the activation mechanism. The terms “distal,” “front,” “frontward,” “depressed,” or “forward” refer generally to an axial direction in the direction “D” of the needle. As used herein, the term “glass” should be understood to include other similarly non-reactive materials suitable for use in a pharmaceutical grade application that would normally require glass. The term “plastic” may include both thermoplastic and thermosetting polymers. Thermoplastic polymers can be re-softened to their original condition by heat; thermosetting polymers cannot. As used herein, the term “plastic” refers primarily to moldable thermoplastic polymers such as, for example, polyethylene and polypropylene, or an acrylic resin, that also typically contain other ingredients such as curatives, fillers, reinforcing agents, colorants, and/or plasticizers, etc., and that can be formed or molded under heat and pressure. As used herein, the term “plastic” does not include either glass or elastomers that are approved for use in applications where they are in direct contact with therapeutic liquids that can interact with plastic or that can be degraded by substituents that could otherwise enter the liquid from plastic. The term “elastomer,” “elastomeric” or “elastomeric material” refers primarily to cross-linked thermosetting rubbery polymers that are more easily deformable than plastics but that are approved for use with pharmaceutical grade fluids and are not readily susceptible to leaching or gas migration. “Fluid” refers primarily to liquids, but can also include suspensions of solids dispersed in liquids, and gasses dissolved in or otherwise present together within liquids inside the fluid-containing portions of syringes. The term “spring” is used herein with reference to one or more “biasing members,” and any type of spring or other biasing member may be utilized within the inventions herein. 
       FIG. 1A  and  FIG. 1B  show an embodiment of an automatic injector  100  having a plunger sub-assembly  10 . The automatic injector  100  includes housing  11  that comprises upper housing  14  and lower housing  16 . Upper housing  14  and lower housing  16  may be made of any of a number of materials including plastics, metals, and glass, but are preferably made of plastic. Housing  11  may be one unified or integrally formed component, may be formed from two or more portions or, as shown in  FIGS. 1A and 1B , comprise upper and lower housings  14 ,  16 . When upper housing  14  and lower housing  16  are two separate components they may be fixedly connected, for example by a glue or adhesive, or removably attached, for example by a screw-fit connection. Automatic injector  100  may also include activation mechanism  30  and cap  18 .  FIG. 1B  shows the interior components of automatic injector  100 , i.e., with the upper housing  14  and lower housing  16  hidden from view. As shown in  FIG. 1B , automatic injector  100  includes activation mechanism  30 , plunger sub-assembly  10 , and syringe cartridge  20 . The syringe cartridge  20  includes a barrel  21  and a needle assembly  40  mounted thereto, both of which are shown in  FIG. 2 .  FIG. 2  shows how the plunger sub-assembly  10  and other components are assembled to produce an automatic injector  100 , according to at least one embodiment of the present invention. The automatic injector may also include a sleeve  150  to assist in the positioning of the syringe cartridge  20  and needle assembly  40  throughout operation, as is described further herein with reference to  FIGS. 5-8 . Cap  18  may be removably attached to automatic injector  100  at the distal end D and removed at time of use by the user.  FIG. 1B  shows the components of plunger sub-assembly  10 , the syringe cartridge  20  having needle assembly  40 , and automatic injector  100  (with upper housing  14  removed to show the internal components), according to at least one embodiment of the present invention, in a locked configuration. 
     In at least one embodiment, the activation mechanism  30  comprises button  31  which may, for example, be rotated to unlock the activation mechanism  30  and then depressed to trigger the activation mechanism  30 , as is detailed further herein. The activation mechanism  30  is shown at proximal end P. A tactile biasing member may be utilized, for example, to maintain the activation mechanism  30  in a locked position until manipulation by the user and/or to provide the user with a tactile feedback when the button  31  is depressed. The tactile biasing member may be, for example, a spring, or may comprise interacting surfaces of the upper housing  14  and the activation mechanism  30 , as shown in  FIGS. 5-8 . 
     Typically, syringe cartridge  20  includes a barrel  21  having a drug chamber  22 . A liquid substance or drug dose is held in the drug chamber  22  for delivery through a needle to a patient. Upon depression, i.e., axial motion in the distal direction, activation mechanism  30  permits plunger sub-assembly  10  to actuate the needle insertion and drug dose delivery stages of operation. The plunger sub-assembly  10  also translates plunger inner  110  in the distal direction to subsequently facilitate or initiate the retraction activation stage of operation. Retraction activation by the plunger sub-assembly  10  enables retraction of the needle into the barrel of the syringe cartridge  20  and automatic injector  100 , as is detailed further herein. 
     The automatic injectors  100  of the present invention utilize one or more biasing members, such as compression springs  102 ,  106 , to provide the force necessary to insert the needle into the user, push fluid from the drug chamber  22  of the syringe cartridge  20  out through the needle for drug delivery, and activate a needle retraction safety mechanism. However, it is important to minimize the force necessary to be provided by such biasing members for various manufacturing and operational benefits. For example, a lower force biasing member, which may be more cost-effective than higher force biasing members, may be utilized if reduced forces are needed to perform all of the stages of device operation. Similarly, reducing necessary forces may enable the devices to be stored and transported more readily since the energy stored within the device prior to activation is reduced. Accordingly, the embodiments of the present invention utilize plunger sub-assemblies  10  which require lower forces to initiate activation of the retraction mechanism. Because the plunger inner  110  and the integrated retraction features are driven, or caused to activate, by the plunger sub-assemblies  10 , the plunger sub-assemblies  10  and the automatic injectors  100  of the present invention may be configured to utilize lower force biasing members, such as compression springs  102 ,  106 . Similarly, because the total force necessary to: insert the needle into the user, deliver the drug fluid, and activate the needle retraction mechanism is reduced; a simplified plunger sub-assembly  10  may be utilized to efficiently deliver all of the force necessary for the operation of the device. This advantage of the plunger sub-assemblies  10  of the present invention provides substantial benefits to the manufacturability, stability, and operability of the automatic injectors  100  described herein. 
       FIG. 2  shows an exploded view of an automatic injector  100  comprising plunger sub-assembly  10  according to at least one embodiment of the present invention. As shown, an injection spring  102  may reside within a plunger inner  110 , while a retraction spring  106  may reside between the plunger inner  110  and a plunger outer  104 . This simplified plunger sub-assembly  10  permits the reduction of force necessary for the activation of the automatic injector  100 . 
       FIGS. 3A-3D  further detail the plunger sub-assembly  10 , according to at least one embodiment of the present invention, which is a component of the automatic injector  100 .  FIG. 3A  shows the components of plunger sub-assembly  10  in an exploded view, in addition to upper housing  14 .  FIG. 3B  shows these components, without the upper housing  14 , in an energized state prior to actuation. In at least one embodiment, plunger sub-assembly  10  includes injection spring  102  and plunger inner  110 , and retraction spring  106  and plunger outer  104 . In an energized configuration prior to actuation, the injection spring  102  rests in an energized state substantially within the plunger inner  110 . The injection spring  102  is held in an energized state between, and upon activation caused to act on, a platform  110 E of the plunger inner  110 . In this energized configuration, plunger inner  110  is detachably connected to upper housing  14  within the interior  14 C of the upper portion  14 D of the upper housing  14 , as shown in  FIGS. 3C and 3D . Locking hooks  111 A,B of respective locking members  110 A,B of plunger inner  110  may initially directly engage locking plateau  14 A of the upper housing  14 , which may be caused to disengage therefrom by function of the activation mechanism (not shown) located at an upper portion  14 D of the upper housing  14 . For example, the activation mechanism, or aspects thereof, may cause flexion of the locking hooks  111 A,B to disengage the locking hooks  111 A,B from the locking plateau  14 A of the upper housing  14 . Upon disengagement of the locking hooks  111 A,B from the locking plateau  14 A, the injection spring  102  is permitted to expand from its energized state to axially translate the plunger sub-assembly  10  in the distal direction, as will be further explained herein. 
       FIGS. 3C-3D  provide cross-sectional views of the plunger sub-assembly  10  at least partially within upper housing  14  prior to activation or actuation of the automatic injector  100 .  FIG. 3D  shows a 90 degree axial rotation view of the view shown in  FIG. 3C . As shown, locking hooks  111 A,B of plunger inner  110  initially engage locking plateau  14 A of upper housing  14 . Upon activation of the automatic injector  100  by the activation mechanism  30 , locking hooks  111 A,B are caused to disengage from locking plateau  14 A at housing pass-throughs  14 B. In at least one embodiment, the locking hooks  111 A,B are moved radially inwards (i.e., in the direction of the solid arrows shown in  FIG. 3D ) by corresponding interface surfaces of the activation mechanism  30  upon depression by the user, thereby causing disengagement of the plunger sub-assembly from the locking plateau  14 A. As would be appreciated by an ordinarily skilled artisan, the term “hooks” is an example of any type of engagement mechanism including, for example, prongs, latches, tabs, and the like. Upon such disengagement, injection spring  102  is permitted to expand from its energized state, thereby exerting force upon platform  110 E of the plunger inner  110  and axially translating plunger inner  110  (and plunger sub-assembly  10 ) in the distal direction. Because plunger inner  110  is slidably or detachably engaged with plunger outer  104 , such as by the interaction between one or more engagement prongs  104 A,B at the proximal end of a plunger outer  104  component of the plunger sub-assembly  10  and the engagement slot  110 C of the plunger inner  110 , axial translation of the plunger inner  110  in the distal direction causes the plunger outer  104  (and therefore the entire plunger sub-assembly  10 ) to similarly axially translate in the distal direction (i.e., in the direction of the hatched arrow shown in  FIG. 3D ). Accordingly, the force asserted by the injection spring  102  and the plunger inner  110  of the plunger sub-assembly  10 , upon activation by the user, is utilized in the embodiments of the present invention to insert the needle into the user, to axially translate the plunger sub-assembly  10  in the distal direction to enable drug delivery, and to permit or facilitate activation of the retraction mechanism. 
     Such operation of the plunger sub-assembly  10  is also shown in  FIGS. 5-8 , in which the plunger sub-assembly  10  is incorporated into an automatic injector  100 . As shown in  FIGS. 1B, 2, and 5 , release ring  23  rests upon the proximal end of sleeve  150  to retain the syringe barrel  202  and needle assembly  40  of the syringe cartridge in an initial locked position within the automatic injector  100 . In at least one embodiment, sleeve  150  has one or more protrusion  150 A (visible in  FIGS. 1B and 2 ) that are initially held in position within corresponding notches  16 A (visible in  FIG. 2 ) on the interior surface of lower housing  16 . The notches  16 A may be one or more separate notches, a notched ring around the interior circumference, or a number of other possible configurations which permit the one or more protrusions  150 A to removably engage the notches  16 A. In an initially locked configuration, locking extension  18 A (visible in  FIG. 2 ) of the cap  18  rest against the interior surface of the sleeve  150  and assert a radially outward force to maintain the one or more protrusions  150 A in engagement with notches  16 A of the lower housing  16 . Such an arrangement keeps the internal components of the automatic injector  100  in a substantially fixed and locked position capable of being stored and transported for extended periods of time. This configuration of the sleeve  150  also functions to maintain the position of the syringe barrel  202  and needle assembly  40  within the housing during, for example, removal of the needle shield  52 . Additionally or alternatively, the sleeve  150  may be used to brace against barrel  202  of syringe cartridge  20  to ensure substantially axial alignment of these components during storage, transport, and operation of the actuation mechanism and automatic injector. Upon removal of the cap  18 , protrusions  150 A are permitted to flex radially inwards and disengage from the notches  16 A. Accordingly, these components function as a safety feature and, upon removal of the cap  18 , permit axial translation in the distal direction of the internal components of the automatic injector  100 . The cap  18  may also include one or more surfaces  18 B to engage needle shield  52  such that removal of the cap  18  by the user prior to activation also removes the needle shield  52  from the needle assembly. 
     Axial translation of the syringe cartridge  20  may be associated with axial translation of the sleeve  150  during other stages of operation, through the interaction between the release ring  23  of the syringe cartridge  20  and the proximal end of sleeve  150 . For example, upon removal of the cap  18  and activation of the automatic injector  100  by the user, the actuation mechanism  30  may cause syringe cartridge  20  to move distally in the axial direction for needle insertion. Through the interaction between the release ring  23  and the sleeve  150 , sleeve  150  is also caused to move distally in the axial direction. Sleeve  150  may be translated distally until a bridge portion  150 B of sleeve  150  contacts a corresponding depth limiter  16 B (visible in  FIG. 2 ) on an interior surface of the lower housing  16 . Because of the interaction between release ring  23  and sleeve  150 , limiting the range of motion of sleeve  150  also limits axial translation of release ring  23 , syringe barrel  21 , and syringe cartridge  20  having needle assembly  40 . Accordingly, depth of needle insertion into a user can be controlled by the interaction between the bridge portion  150 B of sleeve  150  and the depth limiter  16 B of lower housing  16 . For example, for intramuscular drug delivery (i.e., delivery into the muscle tissue of a user) the insertion depth may be greater and the depth limiter  16 B may be located in a more distal position within the interior surface of the lower housing. For subcutaneous drug delivery, the depth limiter  16 B may be located in a more proximal position within the interior surface of the lower housing and/or the bridge portion  150 B of the sleeve  150  may be located at a more distal position of sleeve  150 .  FIG. 2  also shows these aspects of sleeve  150 , lower housing  16 , and cap  18  for additional clarity. 
     As described above, the embodiments of the present invention minimize the force necessary to initiate activation of the retraction mechanism. Because the plunger and the integrated retraction features are driven, or caused to activate, by the plunger sub-assembly, the plunger sub-assemblies  10  and the automatic injectors  100  of the present invention may be configured to utilize lower force biasing members, such as compression spring  102 ,  106 . This advantage of the plunger sub-assemblies  10  of the present invention, and their integration into the automatic injectors  100 , provides substantial benefits to the manufacturability, stability, and operability of the novel automatic injectors described herein. In at least one embodiment, as shown in  FIG. 4 , the plunger sub-assembly  10  comprises plunger inner  110  comprising shaft  110 F, platform  110 E, ledge  110 D, engagement slot(s)  110 C, locking members  110 A,B respectively comprising locking hooks  111 A,B and seal-engaging member  110 G, which in this embodiment is a screw-threaded projection at the distal end of plunger sub-assembly  10 . Seal-engaging member  110 E engages complementary, screw-threaded recess  820  of plunger seal  800 . Plunger seal  800  further comprises needle-engaging portion  810 . Plunger sub-assembly  10  further comprises plunger outer  104  having base  104 B and one or more engagement prongs  104 A. Plunger sub-assembly  10  further comprises retraction spring  106  which is mounted between plunger inner  110  and plunger outer  104 , and held in an initial first energized state between ledge  110 D of plunger inner  110  and base  104 B of plunger outer  104 . 
     Initially, engagement prongs  104 A are caused to releasably engage corresponding engagement slots  110 B of plunger inner  110 . Engagement prongs  104 A,B are held in releasable engagement with respective engagement slots  110 A,B by inward radial flexion caused by contact between the engagement prongs  104 A,B and a first inner diameter or inner surface of upper housing  14 . However, engagement prongs  104 A,B of plunger outer  104  are resiliently flexible and flex radially outwards (in the direction of the hollow arrows shown in  FIG. 4 ) when the engagement prongs  104 A,B are no longer compressed or flexed radially inwards by the upper housing  14 . This can occur, for example, when the plunger sub-assembly  10  is caused to axially translate in the distal direction to a portion of the housing (e.g., the lower housing  16 ) having a second inner diameter or inner surface that is wider than the first inner diameter. Once the engagement prongs  104 A,B disengage engagement slots  110 A,B of plunger inner  110 , the plunger outer  104  is disengaged from plunger inner  110  to facilitate expansion of retraction spring  106  (in the direction of the hatched arrow shown in  FIG. 4 ) from a first energized state to a second expanded state as part of the integrated retraction mechanism, as will be described hereinafter. Such embodiments of the plunger sub-assembly  10  provide activation of the retraction mechanism without additional force being applied by the actuation mechanism. Accordingly, without additional force being applied by the actuation mechanism on the plunger sub-assembly  10 , the retraction mechanism of the plunger sub-assembly  10  is permitted to activate once the engagement prongs  104 A,B reach a portion of the lower housing  16  having a second inner diameter or inner surface that is wider than the first inner diameter. Preferably, the second inner diameter is located and dimensioned at a portion of the housing  11  that suitably coincides with the plunger seal  800  pushing out all of the drug fluid through the cannula  411  and activation of the retraction mechanism. In at least one embodiment of the automatic injector  100 , the second inner diameter is located in the upper housing  14 , the lower housing  16 , at the connection between the upper and lower housings  14 ,  16 , and/or at any portion thereof that suitably coincides with the plunger seal  800  pushing out all of the drug fluid through the cannula  411  and activation of the retraction mechanism. 
     In at least one embodiment needle assembly  40  integrates a retraction mechanism as described in International PCT App. No. PCT/AU2010/001677, which is incorporated by reference herein. As shown in  FIG. 9 , such a needle assembly  40  includes retractable needle  410  comprising cannula  411 , needle body  420 , needle seal  430 , retainer  300  and ejector  600 . The needle assembly  40  is mounted into the distal end  24  of barrel  21  of the syringe cartridge  20 .  FIG. 9  shows the components in the retraction activation stage, when contact between plunger seal  800  and needle body  420 , needle seal  430  drives ejector  600  to bear against arms  320 A, B of retainer  300  to thereby cause hook-ends  321 A, B of retainer  300  to disengage from needle body  420  for retraction. Cannula  411  may be a number of fluid tubes but is preferably a rigid needle, such as a rigid steel needle. Prior to or upon retraction activation, plunger recess  860  of plunger seal  800  engages proximal segment  425  of needle body  420  for retraction of needle body  42 - and cannula  411 . The retraction activation stage is detailed further with reference to the operation of automatic injector  100  in  FIGS. 5-8  hereinafter.  FIG. 9  shows just one embodiment of the needle assembly  40  configurable for use within an automatic injector  100 . A number of other needle assemblies having integrated retraction mechanisms may similarly be utilized. For example, in at least one embodiment the needle assembly may integrate a retraction mechanism as described in International PCT App. Nos. PCT/US2012/067793 or PCT/US2014/024781, both of which are incorporated herein by reference, which do not require a needle body and which activate retraction of the cannula generally through contact between the plunger seal and needle seal. 
     Operation of plunger sub-assembly  10  and automatic injector  100  will be described with particular reference to  FIGS. 1, 2, and 3D , and  FIGS. 5-8 . In these embodiments, drug chamber  22  of syringe cartridge  20  contains a fluid suitable for injection into a user. As evident in  FIG. 5 , safety cap  18  (shown also in  FIG. 1A ) is removable from lower housing  16  to allow activation of the automatic injector  100 , insertion of the needle  41  and/or cannula  411  into a recipient, and drug delivery. Initially, activation mechanism  30  is in a locked configuration enabled by the releasable engagement between locking prong(s)  14 E (visible in  FIG. 3C ) of upper housing  14  and locking grooves  32  (visible in  FIG. 1B ) of activation mechanism  30 . Locking grooves  32  may be channels, recesses, detents, or the like along the radial circumference of the activation mechanism, as shown in  FIG. 1B , within which one or more locking prong(s)  14 E may travel. Initially, the locking prongs  14 E are in a position within the locking grooves  30 A which prevents depression of the activation mechanism  30 . The button  31  of activation mechanism  30  may be rotated around the longitudinal axis to an unlocked position, where the locking prongs  14 E are aligned with a portion of the locking grooves  12 A that permits axial depression of the button  31 . Optionally, an activation spring may be retained within the activation mechanism  30  and/or between the activation mechanism  30  and the proximal end P of the upper housing  14 , for example to maintain the activation mechanism  30  in a locked position until user operation and to provide the user tactile resistance upon activation. Additionally or alternatively, the components of the upper housing  14  and the activation mechanism  30  may themselves be utilized to provide the user tactile resistance upon activation, such as by, for example, the interface between an activation surface  33  of button  31  and a corresponding housing surface  14 F. This provides useful user feedback to ensure that the proper injection procedures are followed with the device and that removal of the cap is completed prior to needle insertion and drug injection. 
     In the configurations shown in  FIG. 3D  and  FIG. 5 , locking hooks  110 A,B of plunger inner  110  initially engage locking plateau  14 A of upper housing  14 . After removal of the cap  18  and unlocking of the activation mechanism  30 , the automatic injector  100  may be placed in contact with the target location of the user and activated for insertion of needle  41  and/or cannula  411 , drug delivery, and needle retraction. As described above, removal of the cap  18  may be configured to also remove needle shield  52  from the needle assembly. Similarly, removal of the cap  18  permits one or more protrusions  150 A to flex radially inwards and disengage from the notches  16 A of lower housing  16 . Accordingly, removal of the cap  18  permits axial translation in the distal direction of the internal components of the automatic injector  100 . Upon activation of the automatic injector  100  by the activation mechanism  30 , locking hooks  111 A,B are caused to move radially inwards and disengage from locking plateau  14 A. In at least one embodiment, however, the arrangement of the locking hooks  111 A,B and the locking plateau  14 A may be reversed such that the hooks  111 ,A, B are caused to move radially outwards to disengage from the locking plateau  14 A, as would readily be appreciated by one having ordinary skill in the art. The trigger of activation mechanism  30  is shown as a depression, i.e., distal translation of button  31  in the distance D 2  of  FIG. 5  (in the direction of the hatched arrow), which causes locking hooks  111 A,B to flex inwards and disengage from locking plateau  14 A of the upper housing  14 . Upon such disengagement, injection spring  102  is permitted to expand from its energized state, thereby axially translating plunger inner  110  and plunger sub-assembly  10  in the distal direction (in the direction of the hatched arrow in  FIG. 5 ). This stage initiates needle  41  and/or cannula  411  insertion and drug delivery to the patient. 
       FIGS. 5 and 6  show the automatic injector  100 , in a cross-sectional view, before and after activation. Upon activation of the plunger sub-assembly  10 , injection spring  102  is permitted to expand from its energized state causing axial translation of the plunger inner  110  and plunger sub-assembly  10  in the distal direction. Distal translation of plunger inner  110  causes distal translation of the plunger outer  104  through the interaction between engagement prongs  104 A,B of the plunger outer  104  and the engagement slots  110 A,B of the plunger inner  110 . At least initially, such distal translation causes the entire syringe cartridge  20  to move with the sleeve  150  in the distal direction for needle insertion (i.e., in the direction of the hatched arrow in  FIG. 6 ), as shown in the transition between  FIG. 5  and  FIG. 6 . As described above, sleeve  150  may be translated distally until a bridge portion  150 B of sleeve  150  contacts a corresponding depth limiter  16 B on the interior surface of the lower housing  16 . Because of the interaction between release ring  23  and sleeve  150 , limiting the range of motion of sleeve  150  also limits axial translation of release ring  23 , syringe barrel  21 , and syringe cartridge  20  having a needle assembly  40 . Accordingly, depth of needle  41  and/or cannula  411  insertion into a user can be controlled by the interaction between the bridge portion  150 B of sleeve  150  and the depth limiter  16 B of lower housing  16 . 
     As the sleeve  150  and syringe cartridge are prevented from further distal translation, the force applied by the injection spring  102  on the plunger inner  110  causes plunger inner  110  to translate distally within the barrel  21  of the syringe cartridge  20 . Because the syringe cartridge  20  is prevented from further distal translation, distal translation of the plunger inner  110  within the barrel  21  causes a fluid, such as a liquid drug treatment, to be expelled from drug chamber  22  through cannula  411  of needle assembly  40  and into a user for drug delivery. This is visible in the transition between  FIG. 6  and  FIG. 7 . The dimensions of the components and the lengths of axial travel within the device are configured such that engagement prongs  104 A,B of the plunger outer  104  reach the second inner diameter, such as the interior recesses  16 C of lower housing  16 , substantially at the same time as or after activation of the retraction mechanism within the needle assembly  40 . For example, as shown in  FIG. 7 , in at least one embodiment of the present invention the engagement prongs  104 A,B reach the interior recesses  16 C of lower housing  16  just after engagement between plunger seal  800  and needle seal  430  of needle assembly  40 , effectively ensuring that the recess of needle seal  800  has engagedly captured segment  425  of the needle body  420  of the needle assembly  40  for retraction. The engagement prongs  104 A,B are then able to flex radially outwards (i.e., in the direction of the hollow arrows in  FIG. 7 ) and disengage from engagement slots  110 A,B of plunger inner  110  for activation of the retraction mechanism. As stated above however, the second inner diameter (e.g., interior recesses  16 C) may be located in the upper housing  14 , the lower housing  16 , at the connection between the upper and lower housings  14 ,  16 , and/or at any portion thereof that suitably coincides with the plunger seal  800  pushing out all of the drug fluid through the needle assembly  40  and activation of the retraction mechanism. 
     In at least one embodiment of the present invention, needle retraction is essentially similar to that described in International PCT App. No. PCT/AU2010/001677, and will be briefly described as follows with reference to  FIGS. 7-11 . During delivery of fluid contents, plunger inner  110  moves axially through barrel  21  in the direction of the hatched arrow in  FIG. 7 . As shown in  FIG. 9 , plunger seal  800  bears against needle seal  430 , which in turn bears against ejector  600 . Further to this, ejector ring  610  moves hook-ends  321 A, B of arms  320 A, B of retainer  300  radially outwardly in the direction of the hollow arrows in  FIG. 9 , thereby disengaging needle body  420  from retainer  300  to release needle body  420  and cannula  411  for subsequent retraction. At this point, recessed seat  810  of plunger seal  800  has engaged segment  425  of retractable needle body  420  and recess  860  has received fluid end  412  of cannula  411 . This effectively couples needle body  420  and cannula  411  to plunger inner  110  since plunger inner  110  is connected to the proximal end of plunger seal  800 . 
     As shown in  FIG. 7  and  FIG. 10 , in order for needle body  420  and cannula  411  to retract at the end of delivery of fluid contents, retraction spring  106  must de-energize to a second expanded state, which is facilitated by plunger outer  104  disengaging from plunger inner  110 . This disengagement is without additional force applied by the plunger sub-assembly  10  and, instead, simply by engagement prongs  104 A of plunger outer  104  reaching a portion of the housing  11  (e.g., the lower housing  16 ) having a second inner diameter or inner surface that is wider than the first inner diameter. Accordingly, without additional force being applied by the plunger sub-assembly, the retraction mechanism of the automatic injector  100  is permitted to activate once the engagement prongs  104 A,B reach a portion of the housing  11  (e.g., the lower housing  16 ) having a second inner diameter or inner surface that is wider than the first inner diameter.  FIG. 7  and  FIG. 10  show this portion of the lower housing  16  having a second inner diameter as recesses  16 C of lower housing  16 . As plunger inner  110  and plunger outer  104  are substantially fully depressed (i.e., axially translated in the distal direction as per the hatched arrow) to inject fluid from barrel  21 , the engagement prongs  104 A,B are permitted by the recesses  16 C in lower housing  16  to flex radially outwards and disengage from engagement slots  110 A,B of plunger inner  110  (i.e., in the direction of the hollow arrows). This disengagement allows a retraction biasing member  106 , such as a compression spring, to expand from its energized state and push against ledge  110 D (shown in  FIG. 4  and  FIG. 10 ) of plunger inner  110  to thereby retract (i.e., translate in the proximal direction) plunger inner  110  with plunger seal  800 , needle body  420 , and cannula  411  coupled thereto. Plunger outer  104  remains substantially in contact or connection with recesses  16 C of lower housing  16 , while plunger inner  110  coupled to needle body  420  and cannula  411  is axially translated in the proximal direction by decompression of retraction spring  106 , thereby retracting cannula  411  and needle body  420 . The simplified design of the plunger sub-assembly  10  and the releasable engagement between engagement prongs  104 A, B of plunger outer  104  and engagement slots  110 C of plunger inner  110  greatly reduces the force necessary for activation of the retraction mechanism.  FIG. 8  and  FIG. 11  show the components of the automatic injector  100  with the retraction spring  106  in a second expanded state when needle retraction has completed. At this stage, retractable needle  410  is fully retracted into the housing  11  and/or barrel  20  (i.e., in the direction of the hatched arrow in  FIG. 8  and  FIG. 11 ). This needle retraction is highly desirable as it provides integrated safety features while simultaneously providing a true end of dose indication to the user. 
     Certain optional standard components or variations of automatic injector  100  are contemplated while remaining within the breadth and scope of the present invention. For example, upper or lower housings  14 ,  16  may optionally contain one or more transparent or translucent windows  50 , as shown in  FIG. 1 , to enable the user to view the operation of the automatic injector  100  or verify that drug dose has completed. Additionally, an optional needle shield  52  may be utilized, as shown in  FIG. 5 , to protect cannula  411 . The needle shield  52  may be connected, for example, to cap  18  and removed prior to operation of the automatic injector  100 . Similarly, one or more of the components of automatic injector  100  may be modified while remaining functionally within the breadth and scope of the present invention. For example, as described above, while the housing of automatic injector  100  is shown as two separate components upper housing  14  and lower housing  16 , these components may be a single unified component. Similarly, the interior surface of the housing may contain directional channels or guide paths within which the engagement prongs  104  A,B may translate to ensure rotational alignment of the internal components during operation. Such standard components and functional variations would be appreciated by one having ordinary skill in the art and are, accordingly, within the breadth and scope of the present invention. It will be appreciated from the foregoing that the plunger sub-assemblies  10  and automatic injectors  100  disclosed herein provide an efficient and easily-operated system for automated drug delivery from a drug container, with integrated safety features and true end of dose indication to the user. Additionally the novel embodiments of the present invention minimize the force requirements for activation of the plunger sub-assemblies, and thereby provide a simplified design for low force safety-integrated automatic injectors. 
     Assembly and/or manufacturing of plunger sub-assembly  10 , automatic injector  100 , or any of the individual components may utilize a number of known materials and methodologies in the art. For example, a number of known cleaning fluids such as isopropyl alcohol and hexane may be used to clean the components and/or the devices. A number of known adhesives or glues may similarly be employed in the manufacturing process. Additionally, known siliconization fluids and processes may be employed during the manufacture of the novel components and devices. Furthermore, known sterilization processes may be employed at one or more of the manufacturing or assembly stages to ensure the sterility of the final product. 
     The automatic injector may be assembled in a number of methodologies. In one method, an injection spring may be inserted into a housing and compressed between the housing and the plunger inner by detachably engaging one or more locking hooks of the plunger inner with a locking plateau of the housing. In this configuration, the injection spring is initially maintained in an energized state substantially within an upper portion of the plunger inner. The plunger outer, with the retraction spring, may then be connected to the plunger inner to form the plunger sub-assembly within the housing. Regardless of the injection spring and plunger inner configuration, a syringe cartridge comprising a plunger sub-assembly, barrel, and needle assembly may be inserted into the housing such that a proximal end of the plunger sub-assembly contacts the upper housing in a locked configuration. Alternatively, the plunger outer may be connected to the plunger inner prior to insertion of the components into the housing. For example, in a preferred embodiment, the plunger sub-assembly containing the plunger inner, the injection spring, the plunger outer, and the retraction spring is first assembled and then inserted and locked into an energized position into the upper housing. This enables, for example, rotational alignment of the plunger sub-assembly, prevents shifting of the plunger sub-assembly from a substantially axial alignment, and helps ensure an even distribution of force onto the plunger sub-assembly upon activation of the actuation mechanism. The syringe cartridge may be a number of syringes such as, for example, a prefilled syringe containing a drug treatment. Preferably, the syringe is a prefilled retractable syringe, as described above. The syringe barrel and needle assembly may be assembled into a lower portion of the housing separate from the upper portion containing the actuation mechanism and plunger sub-assembly. This assembly method may facilitate aseptic filling of the barrel within the housing, insertion of the plunger sub-assembly into the barrel, and connection of the upper and lower housing components for final assembly. The method may further include the step of: attaching an activation mechanism to the housing, wherein the activation mechanism is configured to contact the one or more locking hooks of the actuation pill upon activation. The activation mechanism may be positioned such that it is in a locked configuration for, for example, shipping and storage of the automatic injector. Additionally, the method may include the step of attaching a cap having a needle shield aspect, or attaching separate cap and needle shield, to the distal end of the syringe cartridge and automatic injector. 
     As discussed above, a glue or adhesive may be utilized to affix one or more components of the automatic injector to each other. Alternatively, one or more components of the automatic injector may be a unified component. For example, the upper housing and lower housing may be separate components affixed together by a glue or adhesive, a screw fit connection, an interference fit, and the like; or the upper housing and lower housing may be a single unified component. These components may be sterilized individually or together, and may be assembled in a sterile environment or sterilized after assembly. Similarly, the assembly of the embodiments of the present invention may utilize a number of other standard manufacturing practices. 
     The automatic injector may be utilized in a number of different ways. For example, in one embodiment the method of operating an automatic injector includes the step of: (i) disengaging one or more locking hooks of plunger inner or plunger sub-assembly from a locking plateau of a housing, wherein such disengagement permits an injection spring to expand substantially along a longitudinal axis of the housing from its initial energized state. The expansion of the injection spring translates the plunger inner and/or plunger sub-assembly substantially along an axis of the automatic injector in the distal direction. Translation of the plunger inner causes translation of a plunger outer in the distal direction. As one or more engagement prongs of the plunger outer component of the plunger sub-assembly reaches one or more recesses in the inner surface of the housing, the engagement prongs are permitted to disengage from the corresponding engagement slots of the plunger inner. In a preferred embodiment, this disengagement occurs when one or more engagement prongs of the plunger sub-assembly reach a portion of the housing having a wider interior diameter or recess, wherein this occurs just after engagement or contact between plunger seal  800  and needle seal of needle assembly  40 . In at least one embodiment, this configuration effectively ensuring that the recess of needle seal  800  has engagedly captured segment  425  of the needle body of the needle assembly  40  for retraction. The plunger sub-assembly may initially drive the needle insertion and drug delivery into the patient. Subsequently, the plunger sub-assembly may activate the retraction mechanism of the syringe cartridge, as described above. The method may further include the steps of: operating the plunger sub-assembly of the automatic injector to deliver a substance to a recipient. Prior to step (i), the method may further include the step of: unlocking an activation mechanism and activating the activation mechanism, as described above. 
     Throughout the specification, the aim has been to describe the preferred embodiments of the invention without limiting the invention to any one embodiment or specific collection of features. Various changes and modifications may be made to the embodiments described and illustrated without departing from the present invention. 
     The disclosure of each patent and scientific document, computer program and algorithm referred to in this specification is incorporated by reference in its entirety.