WO2020008202A1

WO2020008202A1 - Medicament packaging arrangements

Info

Publication number: WO2020008202A1
Application number: PCT/GB2019/051898
Authority: WO
Inventors: Toby Cowe; Timothy Evans
Original assignee: Owen Mumford Limited
Priority date: 2018-07-05
Filing date: 2019-07-04
Publication date: 2020-01-09
Also published as: EP3836883A1; GB201811057D0; GB2575304A; GB2575304B

Abstract

A coupling element for coupling a medicament cartridge to a hub assembly comprises a body having a generally tubular proximal part for receiving a crimp fitting of a closure of the cartridge in use and a distal part defining a release member chamber for receiving a release member of a hub assembly in use, a securing arrangement for engagement with the crimp fitting of the cartridge to secure the coupling element to the cartridge when the closure is inserted into the proximal part of the body; and one or more sealing formations for engagement with the closure of the cartridge to form a seal between the coupling element and the closure. A cannula assembly comprising the coupling element and a hub assembly is also disclosed. A vent comprising an air permeable sterile barrier material may be provided to vent the release member chamber, thereby to minimise any air pressure difference across the seal.

Description

MEDICAMENT PACKAGING ARRANGEMENTS

FIELD OF THE INVENTION

The present invention relates to packaging for medicaments. In particular, but not exclusively, the invention relates to a cannula assembly having a coupling element for connection to a medicament cartridge and to medicament packaging and medicament delivery devices comprising a medicament cartridge in combination with a cannula assembly.

BACKGROUND TO THE INVENTION

Medicaments for use in injection devices and auto-injectors are typically packaged in a pre-filled syringe having a staked needle, with the needle protected and kept sterile by a removable cap. The pre-filled syringe provides a sterile unit that remains aseptically sealed during installation in a device and during subsequent storage of the device. One disadvantage of this arrangement is that the injection devices must be configured to deliver the medicament through the staked needle of the pre-filled syringe, which may not always be the optimum choice since usually only a single type of primary package is available for a given medicament.

Medicaments may also be packaged in pre-filled cartridges. A conventional medicament cartridge typically comprises a tubular glass barrel with a reduced- diameter neck having an annular collar. The neck end of the cartridge is closed by an elastomeric septum, which is held in place by a metal crimp fitting that is crimped over the collar of the neck. Such cartridges are often used in re-usable pen-type injection devices in which a disposable double-ended needle can be attached to the device before each use. When the needle is attached, the proximal end of the needle pierces the septum of the cartridge to create a flow path to the distal end of the needle. When the needle is removed, the septum “self-heals” to re-seal the cartridge. The present applicant’s International Patent Application Publication No. WO 2017/009640 A1 , the contents of which are hereby incorporated by reference, describes medicament packages in which the medicament is contained within a cartridge that is sealed with a sealing element in the form of a septum. The cartridges are arranged to engage with devices that include a release member that is arranged to pierce the septum when the cartridge is inserted into the device. This arrangement allows greater choice in the type of cannula used to deliver the medicament, whilst maintaining the advantages of a simple, universal primary package.

In some embodiments disclosed in WO 2017/009640, the cartridge is arranged to engage with the device in two positions. In a first engagement position, the release member is spaced from the septum so that the medicament remains sealed in the cartridge. The device can be sold, transported and handled in this state. To prepare the device for delivery of the medicament, the cartridge is moved into a second engagement position relative to the device, in which the release member pierces the septum to allow the medicament to flow to the cannula.

In these cases, care must be taken to achieve and maintain the sterility of substantially the whole device before and during installation of the cartridge and during subsequent storage and transportation of the assembled device. As a consequence, the cartridges used in such devices are not conventional, but instead a special fitting must be used at the distal end of the cartridge so that the release member can be sealed in a chamber next to the septum when in the first engagement position.

It is against that background that the present invention has been devised.

SUMMARY OF THE INVENTION

According to a first aspect of the invention, there is provided a coupling element for coupling a medicament cartridge to a hub assembly. The cartridge comprises a generally tubular barrel defining a medicament chamber and having a distal end and a collar adjacent to the distal end, and a closure comprising a sealing element disposed at the distal end of the barrel and a deformable crimp fitting which is crimped over the collar to secure the sealing element to the barrel. The hub assembly comprises a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula. The coupling element comprises a body having a generally tubular proximal part for receiving the crimp fitting of the cartridge in use and a distal part defining a release member chamber for receiving a release member of the hub assembly in use, a securing arrangement for engagement with the crimp fitting of the cartridge to secure the coupling element to the cartridge when the closure is inserted into the proximal part of the body, and one or more sealing formations for engagement with the closure of the cartridge to form a seal between the coupling element and the closure.

With this arrangement, a medicament cartridge with a conventional crimp-type closure can be coupled to a hub assembly. As a result of the seal formed between the coupling element and the closure, the release member can be aseptically sealed in the release member chamber in use. Furthermore, the seal may be formed and the coupling element secured to the cartridge in a single step, by pushing the coupling element and cartridge together so that the securing arrangement engages with the crimp fitting of the cartridge.

Preferably, the securing arrangement comprises one or more clip formations arranged to engage with the crimp fitting.

Preferably, the sealing formation or at least one of the sealing formations comprises one or more projections on an inner surface of the body for engagement with an outer surface of the closure.

For example, the sealing formation or at least one of the sealing formations may comprise at least one circumferential projection arranged to bear against a tubular part of the crimp fitting. The or each circumferential projection may be disposed on a circumferential wall of the proximal part.

The sealing formation or at least one of the sealing formations may comprise an annular projection arranged to bear against a distal end face of the crimp fitting. The sealing formation or at least one of the sealing formations may comprise an annular projection arranged to bear against a distal side of the sealing element. In such cases, the body may comprise a shoulder formed between the proximal part and the distal part, and the or each annular projection may be disposed on a proximal side of the shoulder.

In another example, the sealing formation or at least one of the sealing formations may comprise an O-ring for engagement with the crimp fitting. The body may comprise a groove for retaining the O-ring. The O-ring may be disposed to engage with a distal end face of the crimp fitting. In this way, the O-ring can be compressed between the body of the coupling element and the crimp fitting to form the seal.

The proximal part of the body preferably comprises the securing arrangement. In this way, the coupling element can be formed as a single part. When the securing arrangement comprises one or more clip formations, a plurality of slots may be provided in the proximal part of the body to define the or each clip formation therebetween. For example, a plurality of slots may be provided to define a plurality of clip formations therebetween. The coupling element may be formed from a plastics material, a metal material or any other suitable material.

In a second aspect, the present invention resides in a cannula assembly for connection to a medicament cartridge, comprising a hub assembly comprising a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula, and a coupling element according to the first aspect of the invention for coupling the hub assembly to the cartridge. Preferably, the hub assembly is engageable with the coupling element in a starting configuration in which the release member is spaced from the sealing element and is sealed in the release member chamber, and the hub assembly is moveable relative to the coupling element to switch the cannula assembly into an activated configuration in which the release member cooperates with the sealing element to connect the medicament chamber to the cannula in use.

Advantageously, the cannula assembly may comprise a vent for venting the release member chamber to equalise pressure across the seal. In this way, the likelihood of leakage across the seal is reduced. In turn, this means that, in embodiments of the invention, a suitably reliable seal can be achieved between the coupling element and a conventional crimp-type cartridge closure by a simple interference contact between a projection or other sealing formation formed on the body of the coupling element with the crimp fitting of the cartridge closure, without the need for an elastomeric sealing element such as an O-ring.

Preferably, the vent comprises an air permeable sterile barrier material. The cannula assembly may comprise a removable cap member defining a cannula chamber for receiving the cannula such that at least a distal end of the cannula is sealed in the cannula chamber when the cap member is in place. The vent is preferably disposed in the cap member for venting the cannula chamber. In this case, the release member chamber is also vented due to the fluid flow path provided between the release member chamber and the cannula chamber by the cannula and the release member. In an alternative arrangement, the vent is disposed in the coupling member.

When a cap member is provided, the cap member may comprise at least one blocking formation for limiting relative movement between the hub assembly and the coupling element in at least one direction, thereby to keep the cannula assembly in the starting configuration when the cap member is in place. In use, the blocking formation prevents accidental switching of the cannula assembly to the activated configuration, for example by dropping of the assembly or a device in which the assembly is fitted. The blocking formation is also useful when fitting the cannula assembly to a cartridge, since the blocking formation allows the transmission of force from the cap member to the coupling element without causing the cannula assembly to switch to the activated configuration.

The hub assembly preferably comprises a hub body. A further seal may be formed between the hub body and the coupling element to seal the release element chamber at least when the cannula assembly is in the starting configuration.

The hub body may comprise one or more inwardly-extending clips that cooperate with a collar of the coupling element upon engagement of the hub assembly with the coupling element to guard against subsequent removal of the hub assembly from the coupling element.

The coupling element may further comprise a detent formation on a distal side of the collar to engage with the or each clip to resist relative movement between the hub assembly and the coupling element until a threshold force is applied to switch the cannula assembly into the activated configuration, so as to guard against unintentional switching of the cannula assembly. The coupling element may comprise a further collar for engagement with the or each clip of the hub assembly when the cannula assembly is in the activated configuration to lock the cannula assembly in the activated configuration.

In a third aspect of the present invention, a medicament packaging assembly is provided, the medicament packaging assembly comprising a cannula assembly according to the second aspect of the invention, and a medicament cartridge engaged with the coupling element.

In a fourth aspect, the invention resides in a medicament delivery device comprising a medicament packaging assembly according to the third aspect of the invention, and a drive mechanism for expelling medicament from the medicament cartridge through the cannula. In a fifth aspect, the invention provides a method for assembling a medicament packaging assembly, comprising inserting into a receptacle a cannula assembly according to the second aspect of the invention, inserting into the receptacle a medicament cartridge having a closure comprising a sealing element disposed at the distal end of the cartridge and a deformable crimp fitting to secure the sealing element to the cartridge, and engaging the medicament cartridge with the coupling element of the cannula assembly. Preferably, the method comprises sterilising the cannula assembly and the receptacle after inserting the cannula assembly into the receptacle. In this way, the cannula assembly and the receptacle can be introduced into a sterile cartridge filling line so that a filled cartridge can be engaged with the cannula assembly in a sterile environment. The receptacle may be part of a tray. The tray may include a plurality of such receptacles for assembly of a corresponding plurality of packaging assemblies.

In a sixth aspect, the invention provides a method for connecting a cannula to a medicament cartridge having a closure comprising a sealing element disposed at the distal end of the cartridge and a deformable crimp fitting to secure the sealing element to the cartridge. The method comprises securing a coupling element according to the first aspect of the invention to the closure to form a seal between the coupling element and the closure, and engaging a hub assembly with the coupling element, the hub assembly comprising a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula, such that the release member is received in the release element chamber of the coupling element. When the securing arrangement comprises one or more clip formations, securing the coupling element to the closure may comprise clipping the coupling element to the closure.

In a seventh aspect, the invention resides in a method for connecting a cannula to a medicament cartridge having a closure comprising a sealing element disposed at the distal end of the cartridge and a deformable crimp fitting to secure the sealing element to the cartridge, the method comprising engaging a hub assembly with a coupling element according to the first aspect of the invention, the hub assembly comprising a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula, such that the release member is received in the release element chamber of the coupling element, and securing the coupling element to the closure to form a seal between the coupling element and the closure. When the securing arrangement comprises one or more clip formations, securing the coupling element to the closure may comprise clipping the coupling element to the closure.

Preferred and/or optional features of each aspect of the invention may be used, alone or in appropriate combination, in the other aspects also.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which like reference numerals are used for like features, and in which:

Figure 1 is a cross-sectional view of part of a medicament cartridge together with a coupling element according to an embodiment of the invention, before assembly;

Figure 2 is a cross-sectional view showing the medicament cartridge and coupling element component of Figure 1 when assembled, together with a hub assembly;

Figure 3 is a cross-sectional view showing the medicament cartridge, coupling element component and hub assembly of Figure 2 when assembled to form a packaging assembly;

Figure 4 is a cross-sectional view showing the packaging assembly of Figure 3 installed in a medicament delivery device;

Figure 5 is a cross-sectional view of the delivery device of Figure 4 after removal of a cap, with the coupling element and hub assembly in a first configuration;

Figure 6 is a cross-sectional view of the delivery device of Figure 4 after removal of the cap, with the coupling element and hub assembly in a second configuration;

Figure 7 is a cross-sectional view showing a packaging assembly according to another embodiment of the invention;

Figure 8 is a sectional view of a coupling element component of the packaging assembly of Figure 7;

Figure 9 is a cross-sectional view showing part of a cartridge fitted with a coupling element component according to a further embodiment of the invention;

Figure 10 is a cross-sectional view showing part of a cartridge fitted with a coupling element component according to a still further embodiment of the invention;

Figure 11 is a cross-sectional view showing part of a cartridge fitted with a coupling element component according to a yet further embodiment of the invention;

Figure 12 is a cross-sectional view of a cartridge tray for use with embodiments of the invention and having a plurality of receptacles;

Figure 13 is a perspective view of the tray of Figure 12;

Figure 14 is a cross-sectional view showing a receptacle of the cartridge tray of Figure 12 in more detail;

Figure 15 is a cross-sectional view showing part of the cartridge tray of Figure 12 with cannula assembly received in a first receptacle, a cannula assembly and a cartridge received in a second receptacle before connection of the cartridge to the coupling element, and a cannula assembly and a cartridge received in a third receptacle after connection of the cartridge to the cannula assembly; and

Figure 16 is a cross-sectional view showing part of the cartridge tray of Figure 12 in which all of the receptacles contain a cartridge connected to a cannula assembly.

Throughout this specification, the term“distal” and related terms are used to refer to the end of the component, packaging assembly or device that is closest to the injection site in use (i.e. uppermost in the Figures), and the term“proximal” and related terms are used to refer to the opposite end of the component, packaging assembly or device (i.e. lowermost in the Figures).

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Figure 1 shows the distal end of a medicament cartridge 100. The cartridge 100 comprises a generally tubular barrel 102 that defines a medicament chamber 104 for containing a medicament. The barrel 102 has a reduced-diameter neck 106 at its distal end, and an annular flange or collar 108 extends around the neck 106. A piston member comprising a stopper or bung (not shown) is inserted into the proximal end of cartridge to close the proximal end of the medicament chamber 104.

As is known in the art, the distal end of the cartridge 100 is closed by a closure 1 10 comprising a sealing element in the form of a disc-shaped septum 1 12 made from an elastomeric material such as silicone rubber, and a crimp fitting 1 14 made from a ductile material such as aluminium. The crimp fitting 1 14 comprises a distal end face 1 16 having a central circular aperture 1 18. A tubular wall 120 extends proximally from the end face 1 16 to embrace the collar 108 of the barrel 102. A proximal end part 122 of the tubular wall 120 is deformed inwardly by crimping during assembly of the cartridge 100 so that the proximal end part 122 bears against the proximal side of the collar 108 and so that the end face 1 16 is pulled in the proximal direction. In this way, the crimp fitting 1 14 clamps the septum 1 12 against the distal end face 124 of the barrel 102 so that a seal is formed between the septum 1 12 and the end face 124 of the barrel 102.

Referring to Figures 1 and 2, the cartridge 100 is engageable with a coupling element 150 according to an embodiment of the invention. The coupling element 150 is shown separated from the cartridge 100 in Figure 1 and attached to the cartridge 100 in Figure 2.

The coupling element 150 includes a body 152 having a generally tubular proximal part 154 and a generally tubular distal part or throat 156. The distal part 156 has a smaller diameter than the proximal part 154 and the proximal and distal parts 154, 156 are connected by an annular shoulder 158.

A plurality of clip formations 160 are formed at the proximal end of the proximal part 154 of the coupling element body 152. As can be seen most clearly in Figure 1 , a plurality of notches or slots 162 extend distally from the proximal end of the proximal part 154 to separate adjacent clip formations 160. The free proximal end 164 of each clip formation 160 is turned inwardly towards a central axis of the coupling element body 152.

The coupling element 150 is formed from a resilient material such as a rigid plastics material or a metal material. The clip formations 160 can be splayed outwardly to allow the closure 1 10 of the cartridge 100 to pass into the proximal part 154 of the body 152 during assembly. As shown in Figure 2, when the closure 1 10 is fully inserted in the proximal part 154 of the body 152, the free end 164 of each clip formation 160 springs back to engage with the crimped proximal end part 122 of the crimp fitting 1 14. In this way, the coupling element 150 can be“snap-fitted” over the closure 1 10 of the cartridge 100 and the clip formations 160 provide a securing arrangement that secures the coupling element 150 to the cartridge 100.

Referring back to Figure 1 , the coupling element 150 includes a sealing formation that is engageable with the closure 1 10 of the cartridge 100 when the coupling element 150 is attached to the cartridge. In this embodiment, the sealing formation comprises a set of annular ribs 166 that extend around the inner wall of the proximal part 154 of the coupling element body 152. In this case, three ribs 166 are provided, but fewer or more ribs could be present.

When the closure 1 10 is received in the proximal part 154, the annular ribs 166 bear against the tubular wall 120 of the crimp fitting 1 14. In this way, a seal S1 is formed between the proximal part 154 of the coupling element body 154 and the closure 1 10.

The bore of the tubular distal part or throat 156 of the coupling element body 152 defines a chamber 168 for receiving a release member of a hub assembly. The hub assembly 200 is shown separated from the coupling element 150 in Figure 2, and attached to the coupling element 150 in a starting position in Figure 3.

The hub assembly 200 comprises a hub body 202 and a cannula in the form of a double-ended hypodermic needle 204. The hub body 202 comprises a generally tubular proximal part 202a and a bell-shaped distal part 202b. The distal end of the hub body 202 has an end face 202c with a central aperture for receiving the needle 204. A tubular cap retaining part 202d surrounds the aperture and extends distally from the end face 202c. The needle 204 is fixed in the aperture by a cannula seal 206, which may for example be of a suitable elastomeric material. A distal end part 204a of the needle 204 projects away from the hub body 202.

A generally tubular boss 208 extends proximally from the end face 202c of the hub body 202, towards the proximal part 202a. A pair of annular ribs 210 are formed on the outer wall of the boss 208. A proximal end part 204b of the needle 204 extends through the boss 208.

As can be seen in Figure 3, the hub assembly 200 can be coupled to the coupling element 150, and indirectly to the cartridge 100. For convenience, the hub assembly 200 and coupling element 150 in combination are referred to hereafter as a cannula assembly 201 , and the hub assembly 200, coupling element 150 and cartridge 100 in combination are referred to hereafter as a packaging assembly 250.

In Figure 3, the packaging assembly 250 is in a starting configuration, in which the proximal end part 204b of the needle 204, which forms a release member for the septum 1 12, projects into the chamber 168 defined by the proximal end part 156 of the coupling element body 152.

The annular ribs 210 bear against the inner wall of the tubular proximal end part 156 to form a seal S2 between the boss 208 and the coupling element 150.

By virtue of the seal S1 between the coupling element 150 and the closure 1 10 of the cartridge 100, and the seal S2 between the coupling element 150 and the boss 208 of the hub body 202, the chamber 168 provides an aseptically sealed compartment for the proximal end part 204b of the needle 204. Thus, provided the components are assembled in sterile conditions, the proximal end part 204b of the needle 204 remains sterile until the hub assembly 200 and the coupling element 150 are moved relative to one another into an activation position, as will be described below.

Distal movement of the hub assembly 200 away from the coupling element 150 is prevented by a clip formation. In this example, the clip formation is formed by a plurality of flexible barbs 202e that extend inwardly from the distal end of the proximal part 202a of the hub body 202 to engage with a collar 156a formed at the distal end of the throat 156 of the coupling element 150. The collar 156a has a ramped distally-facing surface to allow the barbs 202e to pass proximally over the collar 156a as the hub assembly is clipped on to the coupling element 150, and a perpendicular proximally-facing surface to prevent the barbs 202e from passing back over the collar 156a. In this way, the hub assembly 200 is retained on the coupling element 150 after assembly of the packaging assembly 250.

A cap sleeve member 220 is fitted to the distal end of the hub assembly 200. The cap sleeve member 220 has a distally-extending bore 222 that defines, in part, a cap chamber 224 for receiving the distal end part 204a of the needle 204. The cap retaining part 202d of the hub body 202 engages with an interference fit in a proximal end of the bore 222, to form a seal S3 between the cap sleeve member 220 and the hub body 202. In an alternative arrangement (not shown), an O-ring seal is provided between the cap sleeve member 220 and the cap retaining part 202d of the hub body 202.

A small-diameter bore 226 extends proximally from the distal end of the cap sleeve member 220 to connect with the distally-extending bore 222. The small-diameter bore 226 is plugged with a cylindrical closure 228 comprising an air-permeable sterile barrier material, such as available under the registered trade marks Tyvek (DuPont, DE, USA) and Vyon (Porvair PLC., Norfolk, UK). The closure 228 provides a vent that allows air to flow into or out of the cap chamber 224 and the release member chamber 168 (through the flow path provided by the needle 204) to equalise the pressure in the chambers 168, 224. This eliminates pressure gradients across the seal S1 between the closure 1 10 and the coupling element 150, across the seal S2 between the coupling element 150 and the hub body 202, and across the seal S3 between the hub body 202 and the cap sleeve member 220, reducing the risk of failure of these seals. In the absence of the vent, such pressure gradients may arise due to telescoping of the parts during assembly and due to changes in temperature and atmospheric pressure during storage. The sterile barrier properties of the material of the closure 228 prevent microbial contamination of the cap chamber 224.

The cap chamber 224 provides an aseptically sealed compartment for the distal end part 204a of the needle 204. Again, provided the components are assembled in sterile conditions, the distal end part 204a of the needle 204 remains sterile until the hub assembly 200 and the coupling element 150 are moved relative to one another into an activation position, as will be described below.

The cap sleeve member 220 is provided with a plurality of ribs 230. The ribs 230 extend parallel to the longitudinal axis of the cap sleeve member 220 and are disposed in an equi-angular arrangement around the outside of the cap sleeve member 220. In the illustrated example, three ribs 230 are provided, one of which can be seen in Figures 2 and 3, but fewer or more ribs 230 may be present.

Each rib 230 is extended proximally to form a blocking member or blocking finger 230a. Each blocking finger 230a is received in a corresponding aperture in the distal part 202b of the hub body 202.

Referring to Figure 3, with the cap sleeve member 220 in place and the hub assembly 200 fitted on the coupling element 150, the proximal end tip 230b of each blocking finger 230a is positioned to cooperate with the distal end face 156b of the throat 156 of the coupling element 150. Thus movement of the coupling element 150 in a distal direction with respect to the hub assembly 200 or, equivalently, movement of the hub assembly 200 in a proximal direction with respect to the coupling element 150 is blocked by abutment between the blocking fingers 230a and the coupling element 150. The blocking fingers 230a therefore prevent the coupling element 150 and hub assembly 200 from moving out of the starting configuration in which the proximal end of the needle 204 is spaced apart from the septum 1 12. This arrangement advantageously prevents accidental movement of the components out of the starting configuration, for example in the event that the packaging assembly 250 is dropped.

Each rib 230 is also extended distally to form a clip formation 230c. The clip formations 230c are separated from the distal end region of the cap sleeve member 230 by slots 230d, so that the clip formations 230c are flexible. The clip formations 230c are used to couple the packaging assembly 250 to an outer cap of a medicament delivery device 300, as will be explained below.

Once the packaging assembly 250 has been assembled in its starting configuration in a sterile environment, all of the components of the packaging assembly 250 that will come into contact with the medicament in use, as well as the medicament in the medicament chamber 104 and the distal end part 204a of the needle 204 (which passes into the injection site) remain sterile.

One convenient way of assembling the packaging assembly 250 comprises first filling the cartridge 100 with medicament and sealing the cartridge using the septum 1 12 and crimp fitting 1 14 to form the closure 1 10 as is known in the art. Then, the coupling element 150 can be snap-fitted over the closure 1 10, and then the hub assembly 200, with the cap sleeve member 220 pre-attached, can be clipped to the coupling element 150. Alternatively, the hub assembly 200 can be attached to the coupling element 150 to form a pre-assembled cannula assembly 201 , before the coupling element 150 is fitted over the closure 1 10 to secure the cannula assembly 201 to the cartridge 100.

The packaging assembly 250 as a whole can then be installed in a medicament delivery device. Advantageously, the maximum diameter of the packaging assembly 250 corresponds to the diameter of the cartridge 100, with the cap sleeve member 220, the hub body 202 and the coupling element 150 all having smaller diameters than the diameter of the cartridge 100. In this way, the packaging assembly 250 can be inserted into a device housing from the proximal end of the housing.

Figure 4 shows the packaging assembly 250 in its starting configuration when installed in a medicament delivery device 300. Only the distal end of the device 300 is shown in Figure 4. The device 300 may include a manual or automatic means for applying a distally-directed force to the stopper (not shown) of the cartridge 100 to expel medicament, as is generally known in the art.

The device 300 comprises a housing 302 having a generally cylindrical interior space 303 to accept the packaging assembly 250. At a distal end of the housing 302, an outer cap 304 is provided. The outer cap 304 engages with the housing 302 and is removable in use of the device 300.

The device 300 can be assembled by inserting the packaging assembly 250 through a proximal end opening (not shown) of the interior space 303 of the housing 302 and pushing the assembly 250 distally until the clip formations 230c of the cap sleeve member 220 engage in corresponding slots 306 provided in the distal end face of the outer cap 304. A central aperture 308 in the distal end face of the outer cap 304 accommodates the distal end of the closure 228.

The outer cap 304 may be engaged with the housing 302 before the packaging assembly 250 is inserted, or alternatively the packaging assembly 250 could be inserted to the housing 302 and held in place while the outer cap 304 is subsequently attached. In either case, the presence of the blocking formations 230a of the cap sleeve member 220 prevent the packaging assembly 250 from moving out of its starting configuration during the insertion process.

To prepare the device 300 for use, the outer cap 304 can be removed from the housing 302. Because the cap sleeve member 220 is engaged with the outer cap 304, the cap sleeve member 220 is removed along with the outer cap 304, exposing the distal end part 204a of the needle 204 and withdrawing the blocking formations 230a from the hub body 202, as shown in Figure 5.

To operate the device 300, the cartridge 100 is initially moved distally with respect to the housing 302. This causes the coupling element 150 to move distally with respect to the hub assembly 200 into an activated position, so that the throat 156 of the coupling element 150 moves into the distal part 202b of the hub body 202 as shown in Figure 6.

In this configuration, the proximal end part 204b of the needle 204 pierces the septum 1 12 to connect the needle 204 to the medicament chamber 104. The packaging assembly 100, and hence the device, is now in an activated state in which a flow path from the medicament chamber 104 to the distal end of the needle 204 has been established.

Delivery of the medicament through the needle 204 can then take place by displacement of the stopper of the cartridge 100 in the distal direction. Figure 7 shows an alternative embodiment in which only the coupling element 350 differs from the arrangement of Figures 1 to 6, and only the differences will be described in detail.

In this embodiment, the coupling element 350, shown in isolation in Figure 8, includes a detent formation in the form of an annular rib 156c disposed on a distal side of the collar 156a. When coupled to the hub assembly 200 in the starting configuration, as shown in Figure 7, the barbs 202e of the hub body 202 locate between the collar 156a and the annular rib 156c. The collar 156a prevents the hub assembly 200 from moving distally with respect to the coupling element 350. The annular rib 156c provides some resistance to proximal movement of the hub assembly 200 with respect to the coupling element 350, so that a threshold force must be applied to move the hub assembly 200 relative to the coupling element to switch the arrangement into the activated configuration.

The coupling element 350 also includes a further collar 156d disposed towards the proximal end of the throat 156. The further collar 156d also has a ramped distally- facing surface and a perpendicular proximally-facing surface. When the hub assembly 200 moves relative to the coupling element 350 into the activated position, the barbs 202e of the hub body 202 pass over the further collar 156d and engage with its proximal side, locking the hub assembly 200 and the coupling element 350 in the activated position.

Figures 9 to 1 1 show three further variants of coupling elements, in which the seal S1 between the coupling element and the closure 1 10 of the cartridge 100 is achieved in different ways.

In Figure 9, the coupling element 450 has a plurality of annular ribs 166a formed on the proximal side of the shoulder 158. These ribs 166a bear against the distal end face 1 16 of the crimp fitting 1 14 to form the seal S1 between the coupling element 450 and the closure 1 10. In Figure 10, the coupling element 550 does not include annular or circumferential ribs. Instead, an annular groove 553 is formed on the proximal side of the shoulder 158 in which an elastomeric O-ring 555 is located. The seal S1 between the coupling element 550 and the closure 1 10 is formed by compression of the O-ring between the shoulder 158 and the distal end face 1 16 of the crimp fitting.

In Figure 1 1 , the coupling element 650 is provided with a single tubular projection 166b formed on the proximal side of the shoulder 158. The projection 166b is sized to pass through the aperture 1 18 in the distal end face 1 16 of the crimp fitting 1 14 and to bear against the distal side of the septum 1 12 to form the seal S1 between the coupling element 650 and the closure 1 10.

It will be appreciated that a coupling element could have a plurality of sealing formations of different types for forming a plurality of seals S1 in different locations between the coupling element and the closure. In particular, two or more of the sealing formations described with reference to Figures 1 to 1 1 could be combined in a single embodiment.

A method of assembling a medicament packaging assembly according to the present invention will now be described. In the method, a plurality of cannula assemblies, each comprising a coupling element and a hub assembly, are fitted into a cartridge tray. The cartridge tray, with the cannula assemblies, are then sterilised, and the cartridge tray is then introduced into the sterile environment of a cartridge filling line. In the cartridge filling line, a sterile, filled cartridge is attached to each of the cannula assemblies to form a sterile medicament packaging assembly.

The cartridge tray 700, shown in Figures 12 and 13, comprises a shell 702 having a base 704, upstanding side walls 706 and an open top 708. A tray insert 710 comprises a plurality of generally tubular receptacles 712 disposed in an array. The receptacles 712 are supported by a web 714 of the insert 710. The insert 710 is supported on a shoulder 716 of the side walls 706, so that the receptacles 712 extend towards the base 704 of the shell 702. The insert 710 includes apertures 718 to allow air or fluid to flow beneath the insert 710.

Figure 14 shows one of the receptacles 712 in more detail. The receptacle 712 includes a first, relatively large diameter tubular part 720 with an open top 722. The bottom of the first part 720 connects with a second, intermediate diameter part 724. A tapered region 726 connects the second part 724 to a third, small diameter part 728. The third part 728 has an open bottom 730, which is spaced from the base 704 of the shell 702. Each receptacle 712 is attached to the web 714 near the top 722 of the first part 720, and is preferably co-moulded with the web 714.

Figure 15 shows three receptacles 712a, 712b, 712c in the container 700, each at a different stage.

In a first stage of the method, a hub assembly 200 and a coupling element 650 as previously described are connected to one another to form a cannula assembly 601 . In the illustrated example, the coupling element 650 is of the type shown in Figure 1 1 , but it will be understood that any of the other coupling elements described herein could be used instead.

The cannula assembly 601 is inserted into a receptacle 712 through its open top 722, with the hub assembly 200 lowermost. Referring to the first receptacle 712a of Figure 15, the receptacle 712 is shaped and dimensioned so that the cap sleeve member 220 extends through the third part 728 of the receptacle 712 with a clearance therebetween, the hub body 202 is disposed substantially within the tapered region 726 and the second part 724, and the proximal part 154 of the coupling element 150 extends upwardly into the first part 720 of the receptacle 712. The tip of the cap sleeve member 220 of the hub assembly 200 protrudes from the bottom 730 of the receptacle 712 and the clip formations 230c of the cap sleeve member 220 are in contact with the base 704 of the shell 702.

The process can be repeated so that all of the receptacles 712 in the tray 700 contain a cannula assembly 601 . The tray 700 and the cannula assemblies 601 can be sterilised in a manner known in the art, with the apertures 718 in the web 714 of the insert 710 and the open bottom 730 of each receptacle allowing complete sterilisation of the cannula assemblies 601 and the interior of the tray 700.

The sterilised tray 700 is then introduced into the aseptic environment of the cartridge filling line. A filled, sealed cartridge 100 is then inserted downwardly into each receptacle 712 (as shown for the second receptacle 712b in Figure 15), with the closure 1 10 of the cartridge 100.

The cartridge 100 is pushed downwardly so that the closure 1 10 of the cartridge 100 snaps into engagement with the coupling element 650 of each cannula assembly 601 , to form a medicament packaging assembly 250 (as shown for the third receptacle 712c in Figure 15). As previously described, the blocking formations 230a (not visible in Figure 15, see Figure 3) of the cap sleeve member 220 contact the coupling element 650 to prevent movement of the coupling element 650 with respect to the hub assembly 200 as the cartridge 100 is engaged with the coupling element 650.

Figure 16 shows a tray 700 in which all of the receptacles 712 contain an assembled packaging assembly 250. The packaging assemblies 250 can then be removed from the tray and packaged or used in further assembly steps as appropriate.

It will be appreciated that, conveniently, automated processes and suitable machines could be used to introduce cannula assemblies 601 into every receptacle 712 of a tray in a parallel operation, and to introduce cartridges 100 into every receptacle and to engage the cartridges 100 with the cannula assemblies 601 in another parallel operation.

Embodiments of the invention can be used in a wide variety of different types of delivery devices. In particular, the packaging assembly can be used in manual devices in which a plunger can be manually depressed to deliver the medicament, and in auto-injector devices in which one or more of the steps of needle insertion into an injection site, delivery of the medicament, retraction of the needle and shielding the needle may be driven by an energy source such as a spring.

Further variations and modifications may be contemplated. For example, in the illustrated examples, the cannula is a double-ended needle, and the proximal end part of the needle acts as a piercing member for the septum. Flowever, a single- ended needle could be provided for delivery of the medicament, with a separate piercing member being formed integrally with the hub body or as a separate component. It is also conceivable that, instead of a septum, the distal end of the cartridge could be sealed by a valve, rupturable membrane or other sealing device. In such cases the sealing element may be released by a suitable release member, which need not be a piercing member but could instead be arranged to open a valve, rupture a membrane and so on.

The cannula need not be a needle, but could instead be a flexible cannula or other suitable infusion or injection device. The cannula need not be mounted directly in the hub body but could instead be connected to the hub body by a flexible tube or the like.

In the illustrated examples, the air-permeable aseptic closure or vent is provided in a wall of the removable cap member to allow air flow through the wall and into or out of the release member chamber via the cannula chamber and the cannula. The vent can instead be provided in the wall of a different component. For example, the vent could be provided in the wall of the throat of the coupling element, to allow air flow directly into or out of the cannula chamber.

In the illustrated examples, the coupling element is secured to the cartridge by clip formations. It is also possible that the coupling element could be secured to the cartridge by an alternative securing arrangement, such as an interference fit between the coupling element and the crimp fitting, an adhesive applied to the coupling element and/or crimp fitting, or any other suitable arrangement. Further modifications and variations not explicitly described above are also possible without departing from the scope of the invention as defined in the appended claims.

Claims

1. A coupling element for coupling a medicament cartridge to a hub assembly, the cartridge comprising a generally tubular barrel defining a medicament chamber and having a distal end and a collar adjacent to the distal end, and a closure comprising a sealing element disposed at the distal end of the barrel and a deformable crimp fitting which is crimped over the collar to secure the sealing element to the barrel; and the hub assembly comprising a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula; the coupling element comprising: a body having a generally tubular proximal part for receiving the crimp fitting of the cartridge in use and a distal part defining a release member chamber for receiving a release member of the hub assembly in use; a securing arrangement for engagement with the crimp fitting of the cartridge to secure the coupling element to the cartridge when the closure is inserted into the proximal part of the body; and one or more sealing formations for engagement with the closure of the cartridge to form a seal (S1 ) between the coupling element and the closure.

2. A coupling element according to Claim 1 , wherein the sealing formation or at least one of the sealing formations comprises one or more projections on an inner surface of the body for engagement with an outer surface of the closure.

3. A coupling element according to Claim 2, wherein the sealing formation or at least one of the sealing formations comprises at least one circumferential projection arranged to bear against a tubular part of the crimp fitting.

4. A coupling element according to Claim 3, wherein the or each circumferential projection is disposed on a circumferential wall of the proximal part.

5. A coupling element according to any of Claims 2 to 4, wherein the sealing formation or at least one of the sealing formations comprises an annular projection arranged to bear against a distal end face of the crimp fitting.

6. A coupling element according to any of Claims 2 to 5, wherein the sealing formation or at least one of the sealing formations comprises an annular projection arranged to bear against a distal side of the sealing element.

7. A coupling element according to Claim 5 or Claim 6, wherein the body comprises a shoulder formed between the proximal part and the distal part, and wherein the or each annular projection is disposed on a proximal side of the shoulder.

8. A coupling element according to any preceding claim, wherein the sealing formation or at least one of the sealing formations comprises an O-ring for engagement with the crimp fitting.

9. A coupling element according to Claim 8, wherein the O-ring is disposed to engage with a distal end face of the crimp fitting.

10. A coupling element according to any preceding claim, wherein the securing arrangement comprises at least one clip formation for engagement with the crimp fitting.

11. A coupling element according to any preceding claim, wherein the proximal part of the body comprises the securing arrangement.

12. A coupling element according to Claim 11 when dependent on Claim 10, wherein the proximal part of the body comprises a plurality of slots to define the or each clip formation therebetween.

13. A cannula assembly for connection to a medicament cartridge, comprising:

a hub assembly comprising a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula; and

a coupling element according to any preceding claim for coupling the hub assembly to the cartridge.

14. A cannula assembly according to Claim 13, wherein the hub assembly is engageable with the coupling element in a starting configuration of the cannula assembly in which the release member is spaced from the sealing element and is sealed in the release member chamber, and wherein the hub assembly is moveable relative to the coupling element to switch the cannula assembly into an activated configuration in which the release member cooperates with the sealing element to connect the medicament chamber to the cannula in use.

15. A cannula assembly according to Claim 14, comprising a vent for venting the release member chamber to equalise pressure across the seal (S1 ), the vent comprising an air permeable sterile barrier material.

16. A cannula assembly according to Claim 14 or Claim 15, comprising a removable cap member defining a cannula chamber for receiving the cannula such that at least a distal end of the cannula is sealed in the cannula chamber when the cap member is in place.

17. A cannula assembly according to Claim 16 when dependent on Claim 15, wherein the vent is disposed in the cap member for venting the cannula chamber.

18. A cannula assembly according to Claim 16 or Claim 17, wherein the cap member comprises at least one blocking formation for limiting relative movement between the hub assembly and the coupling element in at least one direction, thereby to keep the cannula assembly in the starting configuration when the cap member is in place.

19. A cannula assembly according to any of Claims 14 to 18, wherein the hub assembly comprises a hub body and wherein a further seal (S2) is formed between the hub body and the coupling element to seal the release element chamber at least when the cannula assembly is in the starting configuration.

20. A cannula assembly according to Claim 19, wherein the hub body comprises one or more inwardly-extending clips that cooperate with a collar of the coupling element upon engagement of the hub assembly with the coupling element to guard against subsequent removal of the hub assembly from the coupling element.

21. A cannula assembly according to Claim 20, wherein the coupling element comprises a detent formation on a distal side of the collar to engage with the or each clip to resist relative movement between the hub assembly and the coupling element until a threshold force is applied to switch the cannula assembly into the activated configuration.

22. A cannula assembly according to Claim 20 or Claim 21 , wherein the coupling element comprises a further collar for engagement with the or each clip of the hub assembly when the cannula assembly in the activated configuration to lock the cannula assembly in the activated configuration.

23. A medicament packaging assembly comprising:

a cannula assembly according to any of Claims 13 to 22; and a medicament cartridge engaged with the coupling element.

24. A medicament delivery device comprising: a medicament packaging assembly according to Claim 23; and a drive mechanism for expelling medicament from the medicament cartridge through the cannula.

25. A method for assembling a medicament packaging assembly, comprising:

inserting into a receptacle a cannula assembly according to any of Claims 13 to 24;

inserting into the receptacle a medicament cartridge having a closure comprising a sealing element disposed at the distal end of the cartridge and a deformable crimp fitting to secure the sealing element to the cartridge; engaging the medicament cartridge with the coupling element of the cannula assembly.

26. A method for assembling a medicament packaging assembly according to Claim 25, comprising sterilising the cannula assembly and the receptacle after inserting the cannula assembly into the receptacle.

27. A method for connecting a cannula to a medicament cartridge having a closure comprising a sealing element disposed at the distal end of the cartridge and a deformable crimp fitting to secure the sealing element to the cartridge; the method comprising:

securing a coupling element according to any of Claims 1 to 12 to the closure to form a seal between the coupling element and the closure; and engaging a hub assembly with the coupling element, the hub assembly comprising a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula, such that the release member is received in the release element chamber of the coupling element.

28. A method for connecting a cannula to a medicament cartridge having a closure comprising a sealing element disposed at the distal end of the cartridge and a deformable crimp fitting to secure the sealing element to the cartridge; the method comprising:

engaging a hub assembly with a coupling element according to any of Claims 1 to 12, the hub assembly comprising a cannula and a release member that is cooperable with the sealing element in use to connect the medicament chamber to the cannula, such that the release member is received in the release element chamber of the coupling element; and

securing the coupling element to the closure to form a seal between the coupling element and the closure.