Patent Publication Number: US-2022233779-A1

Title: Improved drug delivery device having a plunger with adjustable length

Description:
TECHNICAL FIELD 
     The invention relates to pre-filled syringes and methods of assembly of pre-filled syringes. 
     BACKGROUND 
     Broadly, syringes comprise a barrel having a hypodermic needle at one end and a plunger configured to move within the barrel such that an inward stroke of the plunger causes a substance contained within the barrel to be expelled from the needle. 
     Syringes may further include some form of safety mechanism to protect healthcare workers from the hypodermic needle after the substance has been injected into a patient. Exemplary syringes may include a sheath for covering the needle, or may cause the needle to retract within the barrel of the syringe. 
     Syringes may be provided to a user pre-filled with a substance (such as a medicament), such that they are ready to use. Pre-filled syringes may therefore be transported to a user with the medicament already contained within the barrel. The fill volume of the pre-filled syringe may vary depending on the dosage of medicament to be dispensed to a user. 
     SUMMARY 
     According to the invention in an aspect, there is provided a method of assembling a pre-filled syringe comprising: setting a length of a plunger rod of a plunger rod assembly; and fitting the plunger rod assembly to a barrel of the syringe, the barrel having an opening at a forward end thereof and comprising a bung positioned therein and creating a volume between the bung and the opening, the volume at least partially filled with a substance for delivery from the syringe, wherein setting the length of the plunger rod assembly comprises at least partially inserting the plunger rod into the barrel such that a forward end of the plunger rod contacts the bung, and wherein, after assembly, the length of the plunger rod defines a separation between the bung and the forward end of the plunger rod. The separation may accommodate expansion of the substance within the barrel. 
     As used herein, the term “fitting” with respect to the plunger assembly being fitted to the barrel encompasses fitting directly and/or indirectly. That is, the plunger rod assembly may be fitted to a handle portion that is in turn fitted to the barrel. 
     Optionally, setting the length of the plunger rod comprises positioning a first portion of the plunger rod with respect to a second portion of the plunger rod. 
     Optionally, the first and second portions of the plunger rod are coupled and the first portion is axially moveable with respect to the second portion, and wherein positioning the first portion with respect to the second portion comprises axially moving the first portion with respect to the second portion. 
     Optionally, the method comprises further insertion of the plunger rod into the barrel, wherein the further insertion results in an axial force acting on the first portion for positioning the first portion with respect to the second portion. It is noted that, because the first portion is axially movable with respect to the second portion, further insertion of the plunger rod into the barrel results in axial compression of the plunger rod. In effect, further insertion of the plunger rod may be considered further insertion of the second portion. 
     Optionally, the first and second portions is telescopically received in the other of the first and second portions. 
     Optionally, setting the length of the plunger rod comprises rotating at least one of the first portion and second portion with respect to the other of the first portion and the second portion. 
     Optionally, setting the length of the plunger rod comprises engaging reciprocal threads of the first portion and the second portion for translating rotational force into axial force and vice-versa, and rotating one of the first portion and second portion with respect to the other of the first portion and the second portion. 
     Optionally, the first portion is a forward portion and the second portion is a rearward portion, the method further comprising: engaging the first portion with a rotational lock to rotationally fix the first portion relative to the barrel before further insertion of the plunger rod into the barrel, such that the second portion rotates relative to the first portion. 
     Optionally, the rotational lock comprises a keyed aperture, a cross section of at least part of the plunger rod corresponding to a shape of the keyed aperture. 
     Optionally, the method further comprises rotationally fixing the second portion with respect to the first portion after fitting the plunger rod assembly to the barrel. 
     Optionally, the method further comprises moving the plunger rod rearward after setting the length of the plunger rod for defining the separation between the bung and the forward end of the plunger rod. 
     Optionally, the plunger rod assembly further comprises a rearward member and at least one leg, the at least one leg slidably engaged, directly or indirectly, with the barrel after fitting of the plunger rod assembly to the barrel, and wherein rotationally fixing the second portion with respect to the first portion comprises engaging the second portion with the rearward member. 
     Optionally, the plunger rod assembly further comprising a forward member for fitting to the barrel and slidably engaged with the at least one leg, the forward member comprising the rotational lock. 
     Optionally, engaging the second portion with the rearward member comprises moving the plunger rod rearward. 
     Optionally, the rearward member comprises at least one aperture for receiving at least one rearwardly extending prong of the second portion, and wherein engaging the second portion with the rearward member comprises inserting the at least one prong into the at least one aperture. 
     Optionally, the method further comprises preventing insertion of the at least one prong into the at least one aperture during further insertion of the plunger rod into the barrel. 
     Optionally, preventing insertion of the at least one prong into the at least one aperture comprises obscuring the at least one aperture. 
     Optionally, obscuring the at least one aperture comprises inserting a stopper into the at least one aperture to prevent the prongs of the rearward portion from being inserted into the at least one aperture. 
     Optionally, the method further comprises removing the stopper from the at least one aperture after fitting the plunger rod assembly to the barrel to allow receipt of the at least one prong within the at least one aperture. 
     According to the invention in an aspect, there is provided a method of assembling a pre-filled syringe comprising: rotating a first portion of a plunger rod of a plunger rod assembly with respect to a second portion of the plunger rod, the first portion and the second portion comprising reciprocal threads for translating rotational force into axial force; setting a length of the plunger rod by rotationally fixing the first portion with respect to the second portion; and fitting the plunger rod assembly to a barrel of the syringe, the barrel having an opening at a forward end thereof and comprising a bung positioned therein and creating a volume between the bung and the opening, the volume at least partially filled with a substance for delivery from the syringe, wherein, after assembly, the length of the plunger rod defines a separation between the bung and a forward end of the plunger rod. The separation may accommodate expansion of the substance within the barrel. 
     Optionally, the plunger rod assembly further comprises a rearward member and at least one leg, the at least one leg slidably engaged, directly or indirectly, with the barrel after fitting of the plunger rod assembly to the barrel, and wherein the first portion is a forward portion rotatable with respect to the second portion before setting the length of the plunger, which is a rearward portion and rotationally fixed with respect to the rearward member. 
     Optionally, rotationally fixing the first portion comprises engaging the first portion with a rotational lock after setting the length of the plunger rod. 
     Optionally, the plunger rod assembly further comprises a forward member for fitting to the barrel and slidably engaged with the at least one leg, the forward member comprising the rotational lock. 
     Optionally, the rotational lock comprises a keyed aperture, a cross section of at least part of the plunger rod corresponding to a shape of the keyed aperture. 
     Optionally, the forward member is engaged with the first portion of the plunger rod, the method further comprising sliding the forward member along the at least one leg to disengage the forward member from the first portion before rotating the first portion. 
     According to the invention in an aspect, there is provided a method of assembling a pre-filled syringe comprising: rotating a first portion of a plunger rod of a plunger rod assembly with respect to a second portion of the plunger rod, the first portion and the second portion comprising reciprocal threads for translating rotational force into axial force; setting a length of the plunger rod of by rotationally fixing the first portion with respect to the second portion in a first direction, and allowing rotation of the first portion with respect to the second portion in a second direction; and fitting the plunger rod assembly to a barrel of the syringe, the barrel having an opening at a forward end thereof and comprising a bung positioned therein and creating a volume between the bung and the opening, the volume at least partially filled with a substance for delivery from the syringe, wherein, after assembly, the length of the plunger rod defines a separation between the bung and a forward end of the plunger rod. The separation may accommodate expansion of the substance within the barrel. 
     Optionally, rotationally fixing the first portion with respect to the second portion in a first direction, and allowing rotation of the first portion with respect to the second portion in a second direction comprises engaging the first portion of the plunger rod with a ratchet. 
     Optionally, the reciprocal threads are arranged to lengthen the plunger rod when a rotational force in the second direction is applied to the first portion of the plunger rod. 
     Optionally, the reciprocal threads are arranged to produce a rotational force in the first direction when a forward axial force is applied to the second portion of the plunger rod. 
     According to the invention in an aspect, there is provided a pre-filled syringe comprising:
         a barrel having an opening at a forward end thereof;   a bung positioned within the barrel to create a volume between the bung and the forward opening, the volume at least partially filled with a substance for delivery from the syringe; and   a plunger rod assembly comprising a plunger rod having an adjustable length configured such that a forward end of the plunger rod is in contact with the bung on fitting the plunger rod assembly to the barrel,   and wherein, when the plunger rod assembly is fitted to the barrel, the plunger rod is moveable rearwards with respect to the barrel to define a separation between the bung and the forward end of the plunger.       

     Optionally, the plunger rod comprises a first portion coupled to a second portion, and wherein the first portion is axially moveable with respect to the second portion to adjust the length of the plunger rod. 
     Optionally, one of the first and second portions is telescopically received in the other of the first and second portions. 
     Optionally, at least one of the first portion and second portion is rotatable with respect to the other of the first portion and second portion. 
     Optionally, the first and second portions comprise reciprocal threads for translating rotational force into axial force and vice-versa. 
     Optionally, the first portion is a forward portion and the second portion is a rearward portion, and wherein the pre-filled syringe further comprises a rotational lock configured to rotationally fix the first portion relative to the barrel. 
     Optionally, the rotational lock comprises a keyed aperture and wherein a cross section of at least part of the plunger rod corresponds to a shape of the keyed aperture. 
     Optionally, the plunger rod assembly further comprises a rearward member configured to engage the second portion to rotationally fix the second portion with respect to the first portion. 
     Optionally, the rearward member is configured to engage the second portion when the plunger rod is moved rearward with respect to the barrel after the plunger rod assembly is fitted thereto 
     Optionally, the rearward member comprises at least one aperture configured to receive at least one rearwardly extending prong of the second portion, and wherein receipt of the at least one rearwardly extending prong within the at least one aperture rotationally fixes the second portion with respect to the first portion. 
     40. A pre-filled syringe according to claim  40 , further comprising a stopper configured to selectively obscure the at least one aperture to prevent the prongs of the rearward portion from being inserted into the at least one aperture. 
     Optionally, the plunger rod assembly further comprises at least one leg configured to be slidably engaged, directly or indirectly, with the barrel after fitting of the plunger rod assembly to the barrel. 
     Optionally, the plunger rod assembly further comprises a forward member configured to be fitted to the barrel and comprising the rotational lock, wherein the forward member is configured to be slidably engaged with the at least one leg. 
     According to the invention in an aspect, there is provided a plunger rod assembly for use with a pre-filled syringe comprising a barrel having an opening at a forward end thereof and a bung positioned within the barrel to create a volume between the bung and the forward opening, the volume at least partially filled with a substance for delivery from the syringe, the plunger rod assembly comprising: a plunger rod having an adjustable length configured such that a forward end of the plunger rod is in contact with the bung on fitting the plunger rod assembly to the barrel, wherein, when the plunger rod assembly is fitted to the barrel, the plunger rod is moveable rearwards with respect to the barrel to define a separation between the bung and the forward end of the plunger. 
     According to the invention in an aspect, there is provided a pre-filled syringe comprising: a barrel having an opening at a forward end thereof; a bung positioned within the barrel to create a volume between the bung and the forward opening, the volume at least partially filled with a substance for delivery from the syringe; and a plunger rod assembly comprising a plunger rod having a first portion and a second portion, the first and second portions comprising reciprocal threads configured to translate relative rotation between the first and second portions into relative axial displacement between the first and second portions; and a rotational lock configured to rotationally fix the first portion with respect to the second portion wherein the plunger rod assembly is configured to be fitted to the barrel and wherein the plunger rod length is adjustable such that, when the plunger rod assembly is fitted to the barrel, a forward end of the plunger rod is separated from the bung. 
     Optionally, the plunger rod assembly further comprises a rearward member and at least one leg, the at least one leg slidably engaged, directly or indirectly, with the barrel after fitting of the plunger rod assembly to the barrel, and wherein the first portion is a forward portion rotatable with respect to the second portion, which is a rearward portion and rotationally fixed with respect to the rearward member. 
     Optionally, the plunger rod assembly further comprises a forward member for fitting to the barrel and slidably engaged with the at least one leg, the forward member comprising the rotational lock. 
     Optionally, the rotational lock comprises a keyed aperture, a cross section of at least part of the plunger rod corresponding to a shape of the keyed aperture. 
     Optionally, the forward member is slidable rearwards along the at least one leg to release the rotational lock. 
     Optionally, when engaged the rotational lock fixes the first portion with respect to the second portion in a first direction, and allows rotation of the first portion with respect to the second portion in a second direction. 
     Optionally, the rotational lock comprises a ratchet. 
     Optionally, the reciprocal threads are arranged to lengthen the plunger rod when a rotational force in the second direction is applied to the first portion of the plunger rod. 
     Optionally, the reciprocal threads are arranged to produce a rotational force in the first direction when a forward axial force is applied to the second portion of the plunger rod. 
     According to the invention in an aspect, there is provided a plunger rod assembly for use with a pre-filled syringe comprising a barrel having an opening at a forward end thereof and a bung positioned within the barrel to create a volume between the bung and the forward opening, the volume at least partially filled with a substance for delivery from the syringe, the plunger rod assembly comprising: a plunger rod having a first portion and a second portion, the first and second portions comprising reciprocal threads configured to translate relative rotation between the first and second portions into relative axial displacement between the first and second portions; and a rotational lock configured to rotationally fix the first portion with respect to the second portion wherein the plunger rod assembly is configured to be fitted to the barrel and wherein the plunger rod length is adjustable such that, when the plunger rod assembly is fitted to the barrel, a forward end of the plunger rod is separated from the bung. 
     According to the invention in an aspect, there is provided a kit of parts comprising the plunger rod assembly according to any disclosed herein (in particular those disclosed above) and a pre-filled syringe. 
     According to the invention in an aspect, there is provided a kit of parts comprising the plunger rod assembly according to any disclosed herein (in particular those disclosed above) and a forward assembly. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is an exploded view of an exemplary pre-filled syringe; 
         FIG. 2  is a partial section view of an exemplary plunger rod assembly; 
         FIGS. 3 a -3 i    show an exemplary pre-filled syringe at different stages of assembly; 
         FIG. 4  shows an exemplary plunger rod assembly; 
         FIG. 5  shows a partial section view of the exemplary plunger rod assembly of  FIG. 4 ; and 
         FIGS. 6 a - g    show an exemplary pre-filled syringe at different stages of assembly. 
     
    
    
     DETAILED DESCRIPTION 
     Generally disclosed herein are pre-filled syringes comprising a barrel having an opening at a forward end thereof and a bung positioned therein. A volume may be created between the bung and the opening, the volume at least partially filled with a substance to be delivered from the syringe. The pre-filled syringe may further comprise a plunger rod moveable within the barrel to drive the bung forwards to deliver the substance through the opening of the barrel. For the remainder of this document, the substance is referred to as a medicament for clarity. This need not be seen as limiting on the scope of the invention as claimed. 
     Typically, assembled pre-filled syringes may be provided to a user in a ready to use state, in which a forward end of the plunger rod is held in contact with the bung, and the bung, in turn, is held in contact with the substance contained within the barrel. The plunger rod and the bung may be held in position such that rearward movement away from the medicament is not possible in an assembled (or pre-use) configuration. 
     The inventors have realised that transporting such pre-filled syringes in low-pressure environments (such as at high altitude) may cause leakage of the medicament, since if the plunger rod and the bung are fixed in position, there is no volume into which the medicament can expand. 
     Exemplary pre-filled syringes may therefore comprise a separation between the bung and a forward end of a plunger rod of a plunger rod assembly when in an assembled condition. In exemplary pre-filled syringes, the separation between the bung and the forward end of the plunger rod accommodates expansion of a medicament in a barrel of the pre-filled syringe, which prevents leaks. 
     Throughout the specification, the term “forward” refers to the end of the safety syringe from which the medicament is delivered. In other words, the forward end of the safety syringe is the end proximal to an injection site during use. The terms “rear” or “rearward” refer to the plunger end of the safety syringe or component thereof. In other words, the term “rearward” means distant or remote from the injection site during use. Other relative terms such as axial, longitudinal and the like are used to aid description of the device and need not be seen as limiting on the scope of the invention as claimed. 
       FIG. 1  shows an exploded view of an exemplary pre-filled syringe  100 . The pre-filled syringe  100  comprises a barrel  102 , having an opening (not visible in  FIG. 1 ) at a forward end, and a bung  104 . 
     The barrel  102  comprises a medicament  108  located in the volume formed between the bung  104  and the forward opening. The medicament  108  is configured for delivery from the syringe to, for example, a patient. 
     The opening may be configured to receive a hypodermic needle (covered by a needle shield  110  in  FIG. 1 ). The hypodermic needle may be hollow. The opening in the barrel  102  creates a fluid path between the barrel  102  and the hollow channel of the hypodermic needle to allow for delivery of the medicament  108  to a patient via the hypodermic needle. 
     The pre-filled syringe  100  may further comprise a plunger rod assembly  112 . The plunger rod assembly may comprise a plunger rod  114 . The plunger rod  114  is configured to be received inside the barrel  102 . When the pre-filled syringe  100  is in use by a user, the plunger rod  114  is configured to move within the barrel  102  on an inward stroke and drive the bung  104  forwards such that the medicament  108  is expelled from the forward opening of the barrel  102  by the bung  104  and through the hypodermic needle. 
     The plunger rod  114  may comprise a first portion (or forward portion)  116 , and a second portion (or rearward portion)  118 . The first portion  116  and the second portion  118  may be coupled and axially moveable with respect to one another such that the length of the plunger rod  114  can be adjusted before assembly of the pre-filled syringe  100  is completed. 
     In the exemplary pre-filled syringe  100  of  FIG. 1 , the second portion  118  is telescopically received in the first portion  116 . The skilled person will however appreciate that in alternative arrangements, the first portion  116  may be telescopically received in the second portion  118 . In other alternative arrangements, the first and second portions may be configured to slide alongside one another. The skilled person will be able to envisage other further configurations. 
     In the exemplary arrangement shown in  FIGS. 1 and 2 , the first portion  116  comprises a first screw thread  120  configured to engage a corresponding second screw thread  122  of the second portion  118 . That is, the first and second portions  116 ,  118  may comprise reciprocal threads  120 ,  122  such that relative rotation between the first and second portions  116 ,  118  is allowable. The reciprocal screw threads  120 ,  122  may be configured to partially translate relative rotation into axial movement of at least one of the first and second portions  116 ,  118  with respect to the other of the first and second portions  116 ,  118 . In this way, the axial position of one of the first portion  116  and second portion  118  with respect to the other of the first portion  116  and second portion  118  can be altered. The skilled person will understand that in alternative arrangements, the first and second portions could comprise corresponding ramped surfaces configured to allow relative rotation between the first and second portions. 
     The plunger rod  114  comprises a forward end  124 . In the exemplary pre-filled syringe  100  of  FIG. 1 , the forward end  124  of the plunger rod  114  is configured to be separated from the bung  106  when the pre-filled syringe is in an assembled configuration, prior to use of the pre-filled syringe. The forward end  124  of the plunger rod  114  may be separated from the bung  104  by a distance less than or equal to the height of the bung  106 . In exemplary pre-filled syringes  100 , the forward end  124  of the plunger rod  114  may be separated from the bung  106  by a distance of 2 mm to 4 mm. For example, the forward end  124  of the plunger rod  114  may be separated from the bung by 2 mm, the forward end  124  of the plunger rod  114  may be separated from the bung by 3 mm, and the forward end  124  of the plunger rod  114  may be separated from the bung by 4 mm. 
     The plunger rod assembly  112  may further comprise a rearward member  130 . The second portion  118  may be engageable and disengageable with the rearward member  130 . In the exemplary pre-filled syringe  100  of  FIG. 1 , the second portion  118  (that is, the rearward portion) of the plunger rod  114  is engageable and disengageable with the rearward member  130 . In exemplary pre-filled syringes, engagement of the second portion  118  and the rearward member  130  may rotationally fix the second portion with respect to the rearward member  130 . In some arrangements, engagement of the second portion  118  and the rearward member  130  may rotationally fix the second portion with respect to the first portion  116 . When the second portion  118  is disengaged from the rearward member  130 , the second portion  118  may be free to rotate with respect to the first portion  116  and/or the rearward member  130 . 
     It is noted that references herein to rotationally fixing features and/or making features free to rotate is, unless otherwise stated, related to fixing features of exemplary devices during assembly and in the assembled state, not during operation of the device. 
     The second portion  118  may comprise at least one rearwardly-extending prong  132  (see also  FIG. 3 a   ) configured to be received in a corresponding aperture  134  of the rearward member  130 . The at least one prong may comprise a barb configured to engage with a surface of the aperture  134  to hold the second portion in engagement with the rearward member  130  and prevent unintended disengagement. The at least one prong  132  may be radially deformable to allow engagement and disengagement of the prong  132  with the surface of the aperture  134  of the rearward member  130 . Exemplary pre-filled syringes  100  may comprise a plurality of rearwardly-extending prongs, for example, a pair of opposed rearwardly-extending prongs. As explained in more detail below, the separation between bung  104  and the forward end  124  of the plunger rod  114  may at least partially depend on a length of the at least one prong  132 . 
     The pre-filled syringe  100  may further comprise a rotational lock  140  (visible in  FIG. 2 ). The plunger rod  114  may be engageable with the rotational lock  140 . The rotational lock  140  may be configured to rotationally fix the first portion  116  relative to the barrel  102  when the first portion  116  is engaged with the rotational lock  140 . 
     In the exemplary pre-filled syringe  100 , the rotational lock  140  comprises a keyed aperture  142  (visible in  FIG. 2 ) corresponding to at least part of the cross-section of the plunger rod  114 . The keyed aperture may be non-circular. In the pre-filled syringe  100  of  FIG. 1 , the cross-section of the first portion (or forward portion)  116  of the plunger rod  114  corresponds to the keyed aperture  142  of the rotational lock  140 , such that when the first portion  116  is engaged with the keyed aperture  142 , rotation of the first portion is prevented. For example, the cross-section of the first portion (or forward portion)  116  of the plunger rod  114  may correspond to a shape of the keyed aperture  142   
     The exemplary pre-filled syringe  100  of  FIG. 1  may further comprise a forward member  148 . The forward member  148  may comprise the rotational lock  140 . The forward member  148  may be configured to engage a handle portion  166  when the pre-filled syringe  100  is in an assembled configuration. 
     The forward member  148  may be slidably engaged with the rearward member  130 . In the exemplary pre-filled syringe of  FIG. 1 , the rearward member  130  comprises a head  150  and legs  152   a ,  152   b . The forward member  148  may comprise channels  154   a ,  154   b  (visible in  FIG. 2 ) configured to receive the legs  152   a ,  152   b . The forward member  148  is therefore slideable along the legs  152   a ,  152   b  of the rearward member  130  to allow axial movement of the forward member  148  relative to the rearward member  130 . 
     In the exemplary pre-filled syringe  100  of  FIG. 1 , the forward member  148  may comprise at least one latch configured to engage a corresponding retaining recess of the rearward member  130 . The exemplary forward member  148  may comprise a pair of latches  156   a ,  156   b  (visible in  FIG. 2 ) configured to engage corresponding retaining recesses  158   a ,  158   b  on the rearward portion  130 . The latches  156   a ,  156   b  may be located at a point along the channels  154   a ,  154   b  of the forward portion  148 . The retaining recesses  158   a ,  158   b  may be located on the legs  152   a ,  152   b  of the rearward portion  130 . The position of the retaining recesses  158   a ,  158   b  along the legs  152   a ,  152   b  may be determined to accommodate different fill volumes of the barrel  102 . The retaining recesses of the exemplary arrangement shown in the figures comprise an angled rearward surface  159   a ,  159   b  that is arranged to allow the prong and the barb to ride over upon application of a rearward force. In this way, the forward member  148  may be moved rearwards. In some arrangements, the latches  156   a ,  156   b  may be resiliently deformable. In such arrangements, the legs  152   a ,  152   b  may deform the latches  156   a ,  156   b  such that the latches ride over a surface of the legs  152   a ,  152   b  when the legs are inserted into the channels  154   a ,  154   b  and moved forwards along the channels  154   a ,  154   b . The latches  152   a ,  152   b  may engage with the retaining recesses  158   a ,  158   b  when the retaining recesses  158   a ,  158   b  are in a position adjacent to the latches  156   a ,  156   b  (such that the latches are able to return to their original, non-deformed position). 
     When the latches  156   a ,  156   b  are engaged with the retaining recesses  158   a ,  158   b , the rearward member  130  is fixed in relation to the forward portion  148 . In exemplary assembled pre-filled syringes, the forward portion  148  may be fixed in relation to the barrel  102 . Therefore, in exemplary assembled pre-filled syringes, when the latches  156   a ,  156   b  are engaged with the retaining recesses  158   a ,  158   b , the rearward member  130  is fixed with respect to the barrel  102 . As such, when the plunger rod  114  is engaged with the rearward member  130  (for example, when the prong  132  is engaged with the aperture  134 ) and the forward member  148 , the plunger rod  114  is axially and rotationally fixed with respect to the barrel  102 . 
     The pre-filled syringe  100  further comprises a forward assembly  162 . The forward assembly  162  comprises a sheath  164  configured to cover the hypodermic needle of the pre-filled syringe after the medicament  108  has been dispensed from the barrel  102 , and a handle portion  166 . 
     The sheath  164  comprises channels  168   a ,  168   b . The channels  168   a ,  168   b  of the sheath  164  correspond to the legs  152   a ,  152   b  of the rearward member  130  and are configured to allow travel of the legs  152   a ,  152   b  within each channel  168   a ,  168   b . The legs  152   a ,  152   b  of the rearward member  130  may be received in the channels  168   a ,  168   b  of the sheath  164  when the pre-filled syringe  100  is in an assembled configuration. The legs  152   a ,  152   b  may be configured to travel within the channels  168   a ,  168   b  of the sheath  164  during use of the pre-filled syringe, for example on an inward stroke of the rearward member  130  and the plunger rod  114 . 
     The legs  152   a ,  152   b  of the rearward portion  130  may comprise sheath contact surfaces  170   a ,  170   b  configured to engage with the sheath  164  during use of the pre-filled syringe  100 , at a point on an inward stroke of the rearward member  130  during use of the pre-filled syringe  100 . The sheath contact surfaces may engage with the sheath  164  by directly contacting a surface of the sheath  164 . In the exemplary pre-filled syringe  100 , the sheath contact surfaces  170   a ,  170   b  are located at a rearward position on the legs  152   a ,  152   b  of the rearward member  130  and are configured to contact a surface of the sheath  172   a ,  172   b  located at a rearward position on the sheath  164  (as shown in  FIG. 2 b   ). In alternative arrangements the sheath contact surfaces may be located at a forward end of the legs  152   a ,  152   b  and configured to contact a surface of the sheath located at a forward position on the sheath  164 . For example, the sheath contact surfaces may be the end faces of the legs  152   a ,  152   b.    
     The sheath  164  is configured to surround an outer wall of the barrel  102 , which defines an inner dimension of the sheath  164 . The sheath  164  comprises an aperture  174  at a forward end. The aperture  174  may be positioned forward of a shoulder of the barrel  102  when the pre-filled syringe is in an assembled configuration. In the exemplary pre-filled syringe  100 , the aperture  174  is of smaller dimension (e.g. diameter) than an inner dimension (e.g. diameter) of the sheath  164 . In exemplary safety syringes, the aperture  174  of the sheath  164  may be of a smaller dimension (e.g. diameter) than the outer wall of the barrel  102 . 
     The exemplary sheath  164  comprises a lip (not visible in  FIG. 1 ). The lip extends radially inwards from an inner wall of the sheath  164  to define the aperture  174 . The lip may extend inwards to a point such that the diameter of the aperture  174  is of smaller diameter than the outer wall of the barrel  102 . The lip may be configured to contact the shoulder of barrel  102  in an assembled configuration. The lip may be configured to contact a forward surface of the shoulder of the barrel  102 . 
     In alternative arrangements, the diameter aperture  174  of the sheath  164  may be larger than the outer wall of the barrel  102 . In such arrangements, the aperture  174  may be positioned at a point along the length of the barrel  102  when the pre-filled syringe is in an assembled state. 
     The handle portion  166  comprises a main body  176  and flanges  178   a ,  178   b  extending laterally from the main body  176 . The main body  176  comprises a portion that surrounds the barrel  102  and is fixed thereto. The flanges  178   a ,  178   b  are configured to receive the index finger and middle finger of a user while the thumb applies a force to the head  150  of the rearward member  130  when using the pre-filled syringe, although any combination of fingers and/or thumb could be used. The handle portion  166  is fixed to the barrel  102  by an aperture configured to receive an end of the barrel  102  at a distal end to the opening coupled to the needle. In the embodiment of  FIG. 1 , the barrel  102  comprises a radially protruding lip that is received by the handle portion  116 , however in alternative arrangements, the handle portion  116  may receive syringe barrels without radially protruding lips. 
     The sheath  164  may be at least partially received within the main body  176  of the handle portion  166 . 
     The handle portion  166  may comprise channels corresponding to the legs  152   a ,  152   b  of the rearward member  130 , such that the legs  152   a ,  152   b  are able to pass through the handle portion  166 . In this way, the rearward portion  130  may move in its stroke relative to the handle portion  166  and, therefore, the barrel  102 . 
     The pre-filled syringe  100  may comprise a coupling arrangement configured to couple the rearward member  130  and the plunger rod  114  such that movement of the rearward member  130  on an inward stroke causes an inward stroke of the plunger rod  114 . The pre-filled syringe  100  may comprise a decoupling arrangement configured to decouple the rearward member  130  and the plunger rod  114 , such that relative movement of the rearward member  130  with respect to the plunger rod  114  is possible. 
     The inventors have realised that there exists a need to provide a method of assembling a pre-filled syringe such that a separation is formed between the bung and the forward end of the plunger rod. Further, there exists a need to provide a method of assembly of a pre-filled syringe that enables a consistent separation between the bung and the forward end of the plunger rod even when there are variations in the volume of medicament contained in the barrel (and therefore variations in the axial position of the bung within the barrel). 
     A method of assembling the pre-filled syringe  100  is described below with reference to  FIGS. 3 a - i   . Exemplary methods comprise setting the length of the plunger rod  114  and fitting the plunger rod assembly  112  to the barrel  102 . As described below, setting the length of the plunger rod  114  may comprise partially inserting the plunger rod  114  into the barrel  102  such that the forward end of the plunger rod  114  contacts the bung  104 . 
     As shown in  FIG. 3 a   , exemplary methods of assembly of the pre-filled syringe  100  comprise engaging the rearward portion  118  of the plunger rod  114  with the rearward member  130 . Engaging the rearward portion  118  with the rearward member  130  rotationally fixes the rearward portion  118  with respect to the rearward member  130 . In the exemplary plunger rod assembly  112 , engaging the rearward portion of the plunger rod  114  comprises engaging the at least one prong  132  with the aperture  134  of the rearward member  130 . 
     As shown in  FIG. 3 b   , the forward portion  116  of the plunger rod  114  may then be engaged with the rearward portion  118 . Specifically, the forward portion  116  may be moved into a position such that the rearward portion  118  is telescopically received by the forward portion  116 . Engagement of the forward portion  116  and the rearward portion  118  causes engagement of the reciprocal screw threads  120 ,  122  of the rearward portion  118  and the forward portion  116 . 
     A rotational force (or axial force) may then be applied to the forward portion  116  in order to position the forward portion  116  with respect to the rearward portion  118 . The reciprocal screw threads  120 ,  122  may partially translate the applied rotational force into an axial force (or axial force into a rotational force) such that the forward portion  116  moves axially relative to the rearward portion  118  (which is rotationally fixed as described above). This allows the axial position of the forward portion  116  with respect to the rearward portion  118  to be altered (and therefore the length of the plunger rod  114  to be altered). 
     Once the first portion  116  has been coupled to the second portion  118  by rotating the forward portion  116  with respect to the rearward portion  118 , the method may further comprise rotationally fixing the forward portion  116  with respect to the barrel and/or the remainder of the plunger rod assembly. This may prevent the plunger rod length being further altered, at least whilst the second portion  118  is rotationally fixed with respect to the remainder of the plunger rod assembly. The initial length of the plunger rod  114  may be different to the assembled length of the plunger rod  114  (that is, the length of the plunger rod  114  when the pre-filled syringe  100  is in an assembled configuration). 
     Rotationally fixing the forward portion  116  with respect to barrel  104  and/or the remainder of the plunger rod assembly may comprise engaging the forward portion  116  with the rotational lock  140 , as shown in  FIGS. 3 c    and  3   d.    
     Engaging the forward portion  116  with the rotational lock  140  comprises engaging the forward member  148  with the forward portion  116  of the plunger rod  114 . The channels  154   a ,  154   b  of the forward member  148  may receive the legs  152   a ,  152   b  of the rearward member  130 . The keyed aperture  142  of the forward member  148  may receive the forward portion  116 , thereby rotationally fixing the first portion  116  with respect to the barrel and the remainder of the plunger rod assembly. 
     The forward member  148  may then be axially moved with respect to the rearward member  130  and the forward portion  116  of the plunger rod  114  until the latches  156   a ,  156   b  of the forward member  148  engage with the retaining recesses  158   a ,  158   b  of the legs  152   a ,  152   b  of the rearward member  130 . For example, the forward member  130  may be axially moved along the legs  152   a ,  152   b  of the rearward member. Once the latches  156   a ,  156   b  and the retaining recesses  158   a ,  158   b  are engaged, the axial position of the forward member  148  with respect to the plunger rod  114  and the rearward member  130  is fixed. Further, because the cross-section of the forward portion  116  of the plunger rod  114  corresponds to the keyed aperture  142  of the rotational lock  140 , as described above, rotation of the forward portion  116  with respect to the barrel and/or the remainder of the plunger rod assembly is prevented. 
     As shown in  FIG. 3 e   , the barrel  102  comprising the bung  104 , the forward opening and the medicament  108  may be inserted into the forward assembly  162 . 
     The plunger rod assembly  112  may then be fitted to the barrel  102  of the pre-filled syringe  100 . 
     As shown in  FIG. 3 f   , prior to fitting the plunger rod assembly  112  to the barrel  102 , the rearward portion  118  of the plunger rod  114  is disengaged from the rearward member  130 . Disengaging the rearward portion  118  from the rearward member  130  may comprise applying a forward axial force to the rearward portion  118  to disengage the at least one prong  132  from the recess  134  of the rearward member  130 . 
     Disengaging the rearward portion  118  from the rearward member  130  rotationally disengages the rearward portion  118  from the rearward member  130 . That is, disengaging the rearward portion  118  from the rearward member allows rotation of the rearward portion  118  with respect to the rearward member. In addition, because the forward member is rotationally fixed by the rotational lock  140 , the second portion  118  is free to rotate with respect to the forward portion  116 . 
     Disengaging the rearward portion  118  further allows axial movement of the forward portion  116  within the keyed aperture (although the forward portion  116  is still rotationally fixed with respect to the rearward portion  118 ). That is, disengaging the rearward portion  118  axially decouples the plunger rod  114  from the rearward member  130 , such that relative axial movement between the plunger rod  114  and the rearward member  130  is possible. 
     The method of assembling the pre-filled syringe may further comprise preventing rotational re-engagement of the rearward portion  118  with the rearward member  130  (see  FIG. 3 g   ). As will be described below, this allows relative rotation between the first portion  116  and the second portion  118  in order to set the length of the plunger rod. 
     In exemplary methods and apparatus, preventing re-engagement of the rearward portion  118  and the rearward member  130  may comprise preventing re-insertion of the at least one prong  132  into the aperture  134  of the rearward member  130 . For example, the method of assembly may further comprise obscuring the aperture  134  of the rearward member by inserting a stopper  180  into the aperture  134 , to prevent the at least one prong  132  of the rearward portion  118  from being re-engaged with the aperture  134 . This prevents the rearward portion  118  from engaging with the rearward member  130  when the plunger rod  114  is moved rearward during further assembly steps (as explained below). 
     The plunger rod assembly  112  may then be fitted to the barrel  102 . Fitting the plunger rod assembly  112  to the barrel  102  may comprise at least partially inserting the plunger rod  114  into the barrel  102  such that the forward end  124  of the plunger rod  114  contacts the bung  104 . Further insertion of the plunger rod into the barrel results in a rearward axial force on the first portion  116  for setting the length of the plunger rod. 
     Fitting the plunger rod assembly  112  to the barrel  102  may further comprise engaging the legs  152   a ,  152   b  of the rearward member  130  with the handle portion  166  and the barrel  102 , such that the rearward assembly  130  is slideable with respect to the barrel  102 . Specifically, the legs  152   a ,  152   b  may be received within channels of the handle portion  166  such that the legs  152   a ,  152   b  are slideable within the channels of the handle portion  166  to allow axial movement of the rearward member  130  with respect to the barrel  102 . 
     Once the plunger rod  114  has been inserted into the barrel  102 , the plunger rod assembly  112  may be moved forward towards the bung  104 . 
     Moving the plunger rod assembly  112  towards the bung  104  moves the plunger rod  114  further into the barrel  104 . This results in the forward end  124  of the plunger rod  114  contacting the bung  104 . The point at which the forward end  124  of the plunger rod  114  contacts the bung  104  may depend on the amount of medicament contained within the barrel  102 , and therefore the axial position of the bung  104  within the barrel  102 . In exemplary methods, the initial length of the plunger rod  114  is set (as described above and shown in  FIG. 3 d   ) such that the forward end  124  of the plunger rod  114  contacts the bung  104  during insertion of the plunger rod  114  within the barrel  102  before the plunger rod assembly  112  is fitted to the barrel. That is, before the forward member  148  engages with the handle portion  166 . 
     Exemplary methods of assembly comprise moving the plunger rod assembly  112  further forwards after the forward end  124  of the plunger rod  114  contacts the bung  104 . Because the plunger rod  114  is rotationally decoupled from the rearward member  130  (as described above), further forward movement of the rearward member  130  results in a rearward axial force on the first portion  116  and therefore the second portion  118 . The second portion  118  moves to meet the rearward member  130 . Specifically, the rearward member  130  is moved further forward until the at least one prong  132  contacts the rearward member  130 . 
     As described above, because the aperture  134  of the rearward member  130  is obstructed, for example by the stopper  170 , the at least one prong  132  is unable to re-engage with the aperture  134 . 
     Once the rearward member  130  contacts the rearward portion  118  of the plunger rod  114 , further forward movement of the rearward member  130  exerts an axial force on the first portion  116  and the rearward portion  118  of the plunger rod  114 . Because further forward movement of the forward portion  116  of the plunger rod  114  is resisted by the medicament  108  contained within the barrel  102  (since the forward end  124  of the plunger rod  114  is in contact with the bung  104 , which in turn is in contact with the medicament  108 ), the axial force causes the rearward portion  118  to rotate due to the reciprocal threads  120 ,  122  on the forward portion  116  and the rearward portion  118 . This rotation is partially translated into axial movement by the reciprocal threads  120 ,  122  and as such, the axial position of the rearward portion  118  with respect to the forward portion  116  is altered. Further forward movement of the rearward member  130  therefore acts to rotate the rearward portion  118  with respect to the forward portion  116  reduce the length of the plunger rod  114 . 
     The further forward movement of the rearward member  130  (and therefore the axial movement of the rearward portion  118  with respect to the forward portion  116 ) continues until the plunger rod assembly  112  is fitted to the barrel  102 . The plunger rod assembly may be fitted to the barrel when the forward member  148  engages with the handle portion  166 . This is shown in  FIG. 3 h   . The length of the plunger rod  114  is then set. 
     The stopper  180  may be removed from the aperture  134  of the rearward member  130 . The plunger rod  114  is then moved rearward, away from the bung  104 , such that the rearward portion  118  of the plunger rod  114  re-engages with the rearward member  130 , as shown in  FIG. 3 i   . Because the length of the plunger rod  114  remains constant during this rearward movement, the rearward movement of the plunger rod  114  causes a separation between the forward end  124  of the plunger rod  114  and the bung  104 . The separation may correspond to the length of the at least one prong  132 . 
     The separation can be predetermined, for example, by adjusting the length of the prongs. For example, if the prongs are 2 mm in length, moving the plunger rod rearwards to engage the prongs with the aperture may result in a rearward movement of the plunger rod of 2 mm, providing a separation of 2 mm between the forward end of the plunger rod and the bung. As such, a consistent separation between the bung and the forward end of the plunger rod when the pre-filled syringe is in an assembled configuration can be achieved regardless of minor variations in fill volumes. 
     Re-engaging the plunger rod  114  and the rearward member  130  rotationally fixes the rearward portion  118  with respect to the remainder of the plunger rod assembly, and therefore the forward portion  116 . As such, once the plunger rod  114  is re-engaged with the rearward member  130 , further relative movement of the forward portion and rearward portion is not possible (until the syringe is used). Further, re-engaging the plunger rod  114  with the rearward member  130  axially coupled the plunger rod  114  and the rearward member  130  such that relative axial movement therebetween is not possible in the assembled configuration. 
     An alternative method of assembling a pre-filled syringe  100  to provide a gap between the bung and the forward end of the plunger rod is described below. The alternative method may comprise setting a length of the plunger rod  114  before fitting the plunger rod assembly to the barrel  102 . Setting the length of the plunger rod  114  may comprise rotating the forward portion  116  with respect to the rearward portion  118  before fitting the plunger rod assembly  112  to the barrel  102 . The reciprocal threads  120 ,  122  of the forward portion  116  and the rearward portion  118  partially translate the rotational force into an axial force to allow the forward portion  116  to be positioned with respect to the rearward portion  118 . Once the length of the plunger rod  114  has been set, the forward portion  116  may be rotationally fixed with respect to the rearward portion  118 . The plunger rod assembly  112  may then be fitted to the barrel  102  without further adjustment of the length of the plunger rod  114 . 
     The method may comprise assembling the plunger rod assembly  112  as described above in respect of  FIGS. 3 a    to  3   c.    
     The skilled person will appreciate that the assembled length (that is, the length of the plunger rod  114  desired in the assembled pre-filled syringe) of the plunger rod could be set in various ways. For example, the assembled length of the plunger rod  114  may be set by rotating the forward portion  116  with respect to the rearward portion  118  until the assembled length is reached. Once the assembled length is reached, the forward portion  116  may be engaged with the rotational lock  140  to rotationally fix the forward portion  116  with respect to the rearward portion  118 , and therefore fix the length of the plunger rod  114 . 
     Alternatively, in arrangements in which the rotational lock  140  comprises the keyed aperture and forms part of the forward member  148 , the forward member may be brought into engagement with the plunger rod  114  before the assembled length of the plunger rod is set. That is, the channels  154   a ,  154   b  of the forward member  148  may receive the legs  152   a ,  152   b  of the rearward member  130 . The keyed aperture  142  of the forward member  148  may receive the forward portion  116 . 
     The forward member  148  may then be moved rearwards, along the legs  152   a ,  152   b  of the rearward member  130 , towards the head  150  of the rearward member  130  until the keyed aperture  142  of the rotational lock  140  disengages from the forward portion  116  of the plunger rod  114 . Once the rotational lock  140  has disengaged from the forward portion  116  of the plunger rod  114 , the forward portion  116  is free to rotate relative to the rearward portion  118 . The assembled length of the plunger rod can then be set by rotating the forward portion  116  with respect to the rearward portion  118  as described above. 
     Once the assembled length of the plunger rod  114  has been set, the forward member  148  may be moved forwards along the legs  152   a ,  152   b  of the rearward member  130  until the rotational lock  140  engages the forward portion  116  of the plunger rod  114 . Specifically, the forward member  148  may be moved along the legs  152   a ,  152   b  until the keyed aperture  142  engages with the forward portion  116  of the plunger rod  114 . 
     The forward member  148  may be moved forwards along the legs  152   a ,  152   b  of the rearward member  130  until the latches  156   a ,  156   b  of the forward member  148  engage with the retaining recesses  158   a ,  158   b  of the legs  152   a ,  152   b  of the rearward member  130 . Once the latches  156   a ,  156   b  and the retaining recesses  158   a ,  158   b  are engaged, the axial position of the forward member  148  with respect to the plunger rod  114  and the rearward member  130  is fixed. Further, because the cross-section of the forward portion  116  of the plunger rod  114  corresponds to the keyed aperture  142  of the rotational lock  140 , as described above, rotation of the forward portion  116  with respect to the rearward portion  118  is prevented. As such, the length of the plunger rod  114  is set to the assembled length. 
     The plunger rod assembly  112  may then be fitted to the barrel  102 . Fitting the plunger rod assembly  112  to the barrel  102  may comprise inserting the plunger rod  114  into the barrel. 
     Fitting the plunger rod assembly  112  to the barrel  102  may further comprise engaging the legs  152   a ,  152   b  of the rearward member  130  with the barrel  102 , such that the rearward member  130  is slideable with respect to the barrel  102 . For example, the legs  152   a ,  152   b  of the rearward member  130  may be engaged with the handle portion  166 . Specifically, the legs  152   a ,  152   b  may be received within channels of the handle portion  166  such that the legs  152   a ,  152   b  are slideable within the channels of the handle portion  166 . 
     Once the plunger rod  114  has been inserted into the barrel  102 , the plunger rod assembly  112  may be moved forward towards the bung  104 . 
     Moving the plunger rod assembly  112  towards the bung  104  moves the plunger rod  114  further into the barrel  102 . The plunger rod assembly  112  may be moved towards the bung  104  until the plunger rod assembly  112  is fitted to the barrel  102 . For example, the plunger rod assembly  112  may be moved towards the bung  104  until the forward member  148  engages with the handle portion  166 . Because the length of the plunger rod  114  is set to the assembled length before the plunger rod assembly  112  is fitted to the barrel  102 , the forward end  124  of the plunger rod  114  does not contact the bung  102  during assembly. As such, when the plunger rod assembly  112  is fitted to the barrel  102 , the forward end  124  of the plunger rod  114  is separated from the bung  104 . 
     In another arrangement, the plunger rod may be inserted into the barrel while the rotational lock  140  is disengaged from the first portion  116 . This will allow rotation of the first portion  116  as the forward end of the first portion contacts the bung. After the plunger rod assembly has been fitted to the barrel, the first portion  116  may be rotated a predetermined number of times in order to set the amount of separation between the forward end of the plunger rod and the bung. The rotational lock may be engaged with the first portion  116  to set the length of the plunger rod. 
       FIG. 4  shows an alternative pre-filled syringe  400 . Many of the features of the pre-filled syringe  400  are similar to the features of the pre-filled syringe  100  of  FIG. 1 , and as such, a description of these features is not given again here. Corresponding reference numerals are used to identify the similar features. 
     The pre-filled syringe  400  comprises a ratchet  488  configured for engagement with the plunger rod  414 . The ratchet  488  is one example of a unidirectional rotational lock and there may be other implementations of this. The ratchet  488  may be configured for engagement with the first portion  416  of the plunger rod  414 . The ratchet  488  may be configured to prevent rotation of the first portion  416  in a first direction, and to allow rotation of the first portion  416  in a second direction (opposite to the first direction). 
     The exemplary ratchet  488  shown in  FIG. 4  comprises a wheel  490  comprising teeth  492 . The ratchet  488  may further comprise a recessed portion  494  configured to receive the wheel  490  and comprising corresponding teeth  496 . The teeth  492  of the wheel  490  and/or the teeth  496  of the recessed portion  494  may be shaped such that rotation of the wheel  490  in the second direction is possible (since the teeth of the wheel  490  are able to pass over the corresponding teeth  496  of the recessed portion  494 ). The teeth  492  of the wheel  490  and/or the teeth  496  of the recessed portion  494  may be shaped such that rotation of the wheel  490  in the first direction results in the engagement of the teeth  492  and the corresponding teeth  496  such that rotation of the wheel  490  in the first direction is prevented. In this example, since the rearward portion  418  is rotationally fixed relative to the rearward member  430 , rotation of the forward portion  416  results in axial movement of forward portion  416 , as described below. The axial position of the forward portion  416  with respect to the rearward portion  418  may be adjusted in intervals using the ratchet  488 . 
     The wheel  490  may be engaged with the first portion  416  such that they rotate together. For example, the wheel  490  may comprise a keyed aperture  442  (see  FIG. 5 ) corresponding to the cross-section of the first portion. In the pre-filled syringe  400  of  FIG. 4 , the cross-section of the first portion (or forward portion)  416  of the plunger rod  414  corresponds to the keyed aperture  442  of the wheel  490 , such that when the first portion  416  is engaged with the keyed aperture  442 , rotation of the first portion  416  relative to the wheel  490  is prevented. 
     In the exemplary pre-filled syringe  400  of  FIG. 4 , the forward member  448  may comprise the recessed portion  494 . As such, the wheel  490  may be received by the forward member  448  and the forward portion  416  of the plunger rod  414  may be received by the wheel  490  (see  FIG. 5 ). 
     A method of assembling the pre-filled syringe  400  is described below with reference to  FIGS. 6 a   - g.    
     As shown in  FIG. 6 a   , the wheel  490  is inserted into the recessed portion  494  of the forward member  448 . 
     In the exemplary pre-filled syringe  400 , the rearward portion  418  of the plunger rod  414  is integral with the rearward member  130 . That is, the rearward portion  418  of the plunger rod  414  cannot be disengaged from the rearward member  130 . In alternative arrangements, the rearward portion may be engageable with and disengageable from the rearward member. In such arrangements, the rearward portion may be engaged with the rearward member. In either arrangement, the rearward portion  418  is rotationally fixed with respect to the rearward member  430 . 
     As show in  FIG. 6 b   , the forward portion  416  of the plunger rod  414  may then be engaged with the rearward portion  418 . Specifically, the forward portion  416  may be moved into a position such that the rearward portion  418  is telescopically received by the forward portion  416 . Engagement of the forward portion  416  and the rearward portion  418  causes engagement of the reciprocal screw threads  420 ,  422  of the rearward portion  418  and the forward portion  416 . 
     A rotational force (or axial force) may then be applied to the forward portion  416  in order to position the forward portion  116  with respect to the rearward portion  418 . The reciprocal screw threads  420 ,  422  may partially translate the applied rotational force into an axial force such that the forward portion  416  moves axially relative to the rearward portion  418  (which is rotationally fixed as described above). This allows the axial position of the forward portion  416  with respect to the rearward portion  418  to be altered (and therefore the length of the plunger rod  414  to be altered), as shown in  FIG. 6   c.    
     Once an initial length of the plunger rod  414  has been set, by rotating the forward portion  416  with respect to the rearward portion  418 , the method may further comprise engaging the forward portion  416  with the ratchet  488 . The initial length of the plunger rod  414  may be different to the assembled length of the plunger rod  114  (that is, the length of the plunger rod  114  when the pre-filled syringe  100  is in an assembled configuration). Specifically, the initial length of the plunger rod  414  may be such that when the plunger rod assembly  412  is fitted to the barrel  402 , the plunger rod  414  does not contact the bung  404 . 
     Engaging the forward portion  416  with the ratchet  488  may comprise inserting the forward portion  416  into the keyed aperture  442  of the wheel  490  of the ratchet  488 . The rearward member  430  may be engaged with the forward member  448 . Engaging the rearward member  430  with the forward member  448  may comprise inserting the legs  452   a ,  452   b  of the rearward member  430  into the channels of  454   a ,  454   b  of the forward member  448 . 
     The forward member  448  may then be axially moved with respect to the rearward member  430  and the forward portion  416  of the plunger rod  414  until the latches  456   a ,  456   b  of the forward member  448  engage with the retaining recesses  458   a ,  458   b  of the legs  452   a ,  452   b  of the rearward member  430 . For example, the forward member  430  may be axially moved along the legs  452   a ,  452   b  of the rearward member. Once the latches  456   a ,  456   b  and the retaining recesses  458   a ,  458   b  are engaged, the axial position of the forward member  448  with respect to the plunger rod  414  and the rearward member  430  is fixed. 
     As shown in  FIG. 6 e   , the barrel  402  comprising the bung  404 , the opening and the medicament  408  may be inserted into the forward assembly  462 . 
     The plunger rod assembly  412  may then be fitted to the barrel  402 , as shown in  FIG. 6 f   . Fitting the plunger rod assembly  412  to the barrel  402  may comprise inserting the plunger rod  414  into the barrel. 
     Fitting the plunger rod assembly  412  to the barrel  402  may further comprise engaging the legs  452   a ,  452   b  of the rearward member  430  with the barrel  402 , such that the rearward member  430  is slideable with respect to the barrel  402 . For example, the legs  452   a ,  452   b  of the rearward member  430  may be engaged with the handle portion  466 . Specifically, the legs  452   a ,  452   b  may be received within channels of the handle portion  466  such that the legs  452   a ,  452   b  are slideable within the channels of the handle portion  466 . 
     Once the plunger rod  414  has been inserted into the barrel  402 , the plunger rod assembly  412  may be moved forward towards the bung  404 . 
     Moving the plunger rod assembly  412  towards the bung  404  moves the plunger rod  414  further into the barrel  402 . The plunger rod assembly  412  may be moved towards the bung  404  until the plunger rod assembly  412  is fitted to the barrel  402 . For example, the plunger rod assembly  412  may be moved towards the bung  404  until the forward member  448  engages with the handle portion  466 . Because the length of the plunger rod  414  is set to the assembled length before the plunger rod assembly  412  is fitted to the barrel  402 , the forward end  424  of the plunger rod  414  does not contact the bung  404  during assembly. 
     Once the plunger rod assembly  412  has been fitted to the barrel  402 , a rotational force may be applied to the forward portion  416  (see  FIG. 6 g   ). A rotational force may be applied to the forward portion  416  in the second direction. This causes the forward portion  416  to rotate with respect to the rearward portion  418 . Due to the reciprocal threads  420 ,  422  on the forward portion  416  and the rearward portion  418 , the rotational force is translated into axial movement of the forward portion  416  with respect to the rearward portion  418 . Rotation of the forward portion  416  with respect to the rearward portion  418  in the second direction is possible due to the ratchet  488 . 
     The forward portion  416  is rotated with respect to the rearward portion  418  until a desired separation between the forward end  424  of the plunger rod  414  is reached. 
     It is noted that many of the features of the exemplary apparatus described above and shown in the drawings may be included in other exemplary apparatus. As such, the different drawings are not necessarily to be considered as separate embodiments and features from one drawing may be transferred to an apparatus in another drawing. It is also noted that any of the features of the pre-filled syringes described herein may be used in a safety syringe apparatus for fitting to a syringe. 
     The skilled person will be able to envisage other pre-filled syringes and features thereof without departing from the scope of the appended claims. In particular, it is noted that one or more features included in one or more drawings may be integrated pre-filled syringes shown in other drawings, as will be appreciated by the skilled person.