Patent Description:
Drug delivery devices allowing for multiple dosing of a required dosage of a liquid medicament, such as liquid drugs, and further providing administration of the medicament to a patient, are as such well-known in the art. Generally, such devices have substantially the same purpose as that of an ordinary syringe. They may be designed as an injection device, e.g. as a pen-type injector.

Drug delivery devices of this kind have to meet a number of user specific requirements. For instance in case of those with diabetes, many users will be physically infirm and may also have impaired vision. Therefore, these devices need to be robust in construction, yet easy to use, both in terms of the manipulation of the parts and understanding by a user of its operation. Further, the dose setting must be easy and unambiguous and where the device is to be disposable rather than reusable, the device should be inexpensive to manufacture and easy to dispose. In order to meet these requirements, the number of parts and steps required to assemble the device and an overall number of material types the device is made from have to be kept to a minimum.

Typically, the medicament to be administered is provided in a cartridge that has a moveable piston or bung mechanically interacting with a piston rod of a drive mechanism of the drug delivery device. By applying thrust to the piston in a distal direction, a predefined amount of the medicament can be expelled from the cartridge.

Drug delivery devices of e.g. pen-injector type typically comprise a distal housing component that serves as a cartridge holder and further comprise a proximal housing component to engage with the distal housing component and being further adapted to accommodate a drive mechanism to operably engage with the cartridge for dispensing a predefined amount of the medicament provided therein.

With drug delivery devices, such like pen-type injectors of disposable or reusable type a needle assembly comprising a needle hub and a double-tipped injection needle is to be removably arranged on a distal dispensing end of the housing of the drug delivery device. Typically, the distal end of the device may serve as a cartridge holder comprising an access opening to receive a proximally extending portion of the needle. The cartridge located in the distal housing portion or cartridge holder typically comprises a piercable seal, such like a septum being penetrable by the injection needle.

Especially with disposable drug delivery devices, wherein the cartridge filled with the medicament is readily disposed and assembled in the housing of the device, counterfeiters or falsifiers may access the cartridge via the dispensing end and may withdraw at least part of the medicament located therein. Since such unauthorized withdrawal of the medicament is not perceivable or detectable by the end user, there may arise a danger of health, when the product contained in the cartridge has been manipulated even prior to a first use of the device.

For instance, Document <CIT> discloses a tamper evident cap for a prefilled syringe barrel.

It is therefore an object of the present invention to improve patient safety and to inhibit unauthorized withdrawal of a medicament from a cartridge being readily assembled in a drug delivery device such as a pen-type injector. A respective anti-counterfeiting means should be cost-efficient and easy to realize. Furthermore, the device should be easy and intuitive in handling by the end user or patient.

In a first aspect the invention relates to a pen-type injector for injecting of a dose of a medicament. In particular, the pen-type injector is an injection device for administering a dose of the medicament by way of injection. The pen-type injector comprises a housing to accommodate a cartridge being at least partially filled with the medicament to be dispensed. The housing, which accommodates the cartridge comprises a dispensing end, preferably at a distal end section thereof, which faces towards the patient. The dispensing end has an access opening which is closed by a tamper-evident or tamper-proof closure.

Prior to a first use and prior to a first insertion of an injection needle into or through the access opening the tamper-evident closure has to be removed or at least appropriately configured by the end user. A broken tamper-evident closure is therefore indicative that the pen-type injector has been manipulated. The end user or patient should be appropriately instructed to make use of the device only when the device comprises an undamaged and non-manipulated tamper-evident closure.

The initially present tamper-evident closure at least inhibits to insert a withdrawal device through the access opening of the dispensing end. Here, it may be sufficient when the tamper-evident closure simply blocks the access opening, thereby effectively hindering a withdrawal device, such like a cannula, to reach through the access opening.

The tamper-evident closure may therefore provide an effective anti-counterfeiting means, inherently indicating when a distal or dispensing end of the pen-type injector has been manipulated.

The tamper-evident closure further comprises an identification member, embedded in the bulk of the closure or being attached to an outer surface thereof. This way, a hybrid closure can be provided, wherein the identification member may for instance comprise a molded RFID chip inside or wherein the identification member may comprise a hologram, a datamatrix- and/or a QR code, e.g. provided on an outside facing surface of the closure.

The identification member enables the user making use of an electronic reading device to identify and to confirm a genuine origin of the pen-type injector. The electronic reading device may be a smartphone or a RFID-reader. Additionally, the identification member may also serve to store and to provide useful information to the user such as e.g. an expiry date, information for use of the medicament and/or of the device, the legal manufacturer and/or a time of a first attempt to break the closure.

In another embodiment the tamper-evident closure is removably disposed at the dispensing end of the housing. The tamper-evident closure may be assembled to or connected with the housing by means of a predetermined breaking structure or by means of a structurally weakened structure. The predetermined breakable connection of tamper-evident closure and housing serves to provide a well-defined and deliberate removal of the tamper-evident closure from the housing.

Instead of a complete separation and removal of the tamper-evident closure from the housing it is also conceivable that the tamper-evident closure is moved or pivoted in a predefined way relative to the housing in order to give way to the access opening. Hence, it is conceivable, that the tamper-evident closure is only partially connected with the housing via a predetermined breaking or scoring structure. Upon breaking of the predetermined breaking structure at least a pivoting of the tamper-evident closure relative to the housing may be enabled.

According to another embodiment, the tamper-evident closure protrudes from the dispensing end of the housing. Typically, the housing comprises a cylindrical or elongated shape, wherein the dispensing end is located at a longitudinal or axial end thereof. Preferably, the tamper-evident closure is designed as a longitudinal protrusion of the housing. Such a protruding tamper-evident structure may be easily gripped, bended, twisted or tilted with respect to the housing in order to give way to the access opening.

Moreover and according to another embodiment, the tamper-evident closure is integrally formed with the housing. Preferably, the housing and the tamper-evident closure may comprise or may be composed of an injection mouldable plastic material. This way, tamper-evident closure and housing of the pen-type injector can be manufactured and assembled in a single manufacturing step, e.g. by way of injection molding.

The colour of the tamper-evident closure might be different to the colour of the housing of the pen-type injector to improve a visual appearance and to implement a warning function of the tamper-evident closure. The colour of the closure may for instance be applied by means of printing, such like pad-printing or tampoprinting, offset-printing or the like or by means of a two- or more-component molding process or any other appropriate or comparable processes.

Typically, the housing and/or the tamper-evident closure may comprise a thermoplastic material, a technical polymer and/or a duroplastic polymer. Among thermoplastic materials, the housing may comprise polyolefins such like polyethylene (PE) or polypropylene (PP). Furthermore, polycarbonate (PC) and/or acrylonitrile butadiene styrene (ABS) may for instance be used as technical polymers. Generally, the material of the tamper-evident closure may be different from the material of the housing in order to improve breakability or hardness.

In a further embodiment the dispensing end of the housing and the tamper-evident closure are mutually and firmly bonded or adhesively interconnected. For instance, the tamper-evident closure may be provided as a separate component bonded or adhesively connected with the dispensing end of the housing. For instance, it may be attached to the housing by means of a peelable foil. This way, also existing delivery devices and respective housing designs could be retrofitted with a tamper-evident closure.

In any case, the mutual interconnection of tamper-evident closure and dispensing end of the housing is of non-resurrecting type. Once the interconnection is abrogated it cannot be re-established. Preferably, tamper-evident closure and dispensing end of the housing are frangibly interconnected.

In a further preferred embodiment, the tamper-evident closure entirely seals the access opening of the housing. Hence, by way of the tamper-evident closure, a distal or dispensing end of the housing can be hermetically sealed. This way the interior of the device can be protected against environmental influence. Ingress of dirt, dust or humidity into the interior of the housing can be therefore effectively prevented.

In a further embodiment, an outer circumference of the tamper-evident closure is larger than the cross section of the access opening. Typically, the tamper-evident closure comprises a disc-like shape, wherein only a radial central portion of the disc is integrally formed or connected with the housing of the pen-type injector. A circumferential, radially outwardly extending portion of the tamper-evident closure may serve as an effective gripping means for effectively inducing a tilting and/or twisting motion of the tamper-evident closure relative to the housing. By increasing the cross section or radial extension of the tamper-evident closure, a force-effect provided by a user can be effectively enhanced due to a kind of a leverage effect.

As a consequence, the radial cross section of a disc-shaped portion of the tamper-evident closure is larger than a stepped down neck portion thereof by way of which the tamper-evident closure is interconnected with the dispensing end of the housing.

In a further embodiment, the outer circumference of the tamper-evident closure comprises a serrated, corrugated or keyed structure. This way, improved grip and a friction-reduced handling of the tamper-evident closure can be provided. Furthermore, correspondingly shaped tools may be used in order to induce a motion, a twisting or tilting of the tamper-evident closure for releasing and/or removing the same from the housing. Especially for an improved counterfeit protection, the use of a specific and appropriate geometry, e.g. of a Torx- or star key-profile of the radial extension of the closure together with a corresponding profile of a means or of a tool to remove the closure, might become necessary.

According to another embodiment, the access opening of the housing is located in a distal end face of a threaded socket of a cartridge holder which is adapted to receive a double-tipped needle assembly. The cartridge holder typically forms a distal or dispensing end of the pen-type injector. Typically, the housing further comprises a body as a proximal housing component which serves to receive or which comprises a drive mechanism, typically having a piston rod to operably engage with a piston of the cartridge. The drive mechanism may further comprise a dose dial and a dose button by way of which the size of a dose to be dispensed can be individually set and subsequently dispensed.

During a dispensing action, the piston rod of the drive mechanism is urged in distal direction, thereby driving the piston of the cartridge towards the distal dispensing end of the cartridge and the housing of the pen-type injector. Distally directed displacement of the piston of the cartridge leads to a respective expelling of the medicament from the cartridge when a double-tipped needle is in fluid communication with the interior volume of said cartridge. The double tipped needle assembly typically comprises a needle hub having a threaded receptacle to be releasably mounted on the threaded socket of the cartridge holder.

Upon screwing the needle assembly onto the threaded socket, a proximally extending tipped needle end pierces and penetrates a distally located seal of the cartridge located inside and fixed by the cartridge holder.

In a further preferred embodiment, the pen-type injector comprises a removable protective cap to releasably cover the dispensing end of the housing of the pen-type injector. Typically, the protective cap serves to cover the complete cartridge holder of the pen-type injector. The protective cap comprises a cupped receptacle to receive the dispensing end of the housing even with the tamper-evident closure assembled thereon. By means of the protective cap, the cartridge holder as well as the dispensing end of the housing of the pen-type injector can be effectively protected again environmental influences, such like dirt, dust and/or humidity.

According to another embodiment, the cap comprises a receptacle at an outside facing portion to receive and/or to engage with the tamper-evident closure. This way, the cap may serve as a tool to grip and to induce a breaking motion onto the tamper-evident seal for removing the same prior to an initial use of the pen-type injector.

It is of particular benefit here, when the receptacle and the tamper evident closure positively engage when the tamper-evident closure is received in the receptacle of the protective cap. This way the cap may effectively provide a tool for removing and/or releasing the tamper-evident closure from the housing.

In a further preferred embodiment, the receptacle to receive and/or to engage with the tamper-evident closure is located at a distal end portion of the protective cap. Removal of the tamper-evident closure then requires to initially remove the protective cap from the pen-type injector, to twist the protective cap by about <NUM>° and to mount the receptacle of the protective cap onto the tamper-evident closure. Then, a releasing or breaking motion of the tamper-evident closure may be induced by means of the protective cap, which according to its geometric structure and a comparatively large diameter compared to the cross section of the tamper-evident closure, may provide a leverage effect.

Moreover, the geometric structure of the protective cap may allow for an easy and intuitive gripping of the cap itself for inducing a twisting motion to the tamper-evident closure relative to the housing or cartridge holder of the pen-type injector.

According to another embodiment, the receptacle comprises a sidewall that mates and corresponds with the outer circumference of the tamper-evident closure. If the tamper-evident closure comprises a serrated, corrugated or keyed structure, the sidewall of the receptacle of the protective cap also comprises a correspondingly shaped serrated, corrugated or keyed structure. This way, a positive engagement comparable to a screw-driver interconnection can be provided allowing to induce a releasing and twisting motion onto the tamper-evident closure relative to the housing or cartridge holder.

According to further embodiment the tamper-evident closure and the receptacle comprise mutually corresponding geometric structures in order to mutually engage for transferring an angular momentum from the protective cap to the tamper-evident closure for releasing and/or removing the same from the dispensing end of the pen-type injector.

Other solutions may include tamper-evident closures that are to be released or to be removed from the dispensing end of the pen-type injector by way of tilting, by way of impressing or by indenting a structurally weakened portion of the interconnection of tamper-evident closure and dispensing end of the housing.

The pen-type injector may be of disposable type having a cartridge readily disposed therein. After use, when the cartridge is substantially emptied the entire pen-type injector is then intended to be discarded instead of replacing the cartridge by a new one.

Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in <NPL>, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.

Antibodies are globular plasma proteins (~150kDa) that are also known as immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

In the following, preferred embodiment of the invention will be described by making reference to the drawings, in which:.

The pen-type injector <NUM> as illustrated in <FIG> comprises a housing having a proximal body <NUM> and a distally located cartridge holder <NUM>. Body <NUM> and cartridge holder <NUM> are mutually interconnected in an interface section <NUM>, in which cartridge holder <NUM> and body <NUM> are arranged in a mutually overlapping or interleaved configuration. There, body <NUM> and cartridge holder <NUM> may be inseparably or permanently interconnected, e.g. by way of welding or by means of an adhesive. Moreover, when designed as a reusable device, body <NUM> and cartridge holder <NUM> may be releasably engaged. For instance, body <NUM> and cartridge holder <NUM> may be threadedly engaged in the interface section <NUM>.

A proximal end of the pen-type injector is provided with a dose dial <NUM> and a proximal dose button <NUM>. By way of turning or twisting the dose dial <NUM>, a size of a dose of a medicament to be dispensed by the device <NUM> can be individually selected and set. Once, a dose has been appropriately set, by means of pushing the dose button <NUM> in distal direction, hence towards the cartridge holder <NUM>, the drive mechanism housed in the body <NUM> may serve to axially displace a piston rod in distal direction for correspondingly urging a piston of a cartridge in distal direction for expelling a predefined amount of the medicament from the cartridge which is positioned in and fixed by the cartridge holder <NUM>. As further illustrated in <FIG>, the cartridge holder <NUM> comprises a shoulder portion <NUM> against which a correspondingly shaped cartridge may axially and/or radially abut when assembled therein.

As illustrated in <FIG> the cartridge holder <NUM> comprises an inspection window <NUM> by way of which a filling level of a vitreous cartridge mounted therein can be visually inspected.

At its distal end the cartridge holder <NUM> comprises a threaded and stepped-down socket <NUM> which is adapted to threadedly receive a double tipped needle assembly. The needle assembly, which is not particularly illustrated here, typically comprises a circular or cylindrically shaped hub having a threaded cylindrical portion to be screwed onto the threaded socket <NUM>. Moreover, the needle assembly comprises a tipped needle end to enter the access opening <NUM> of the cartridge holder <NUM> for piercing and for penetrating a pierceable seal, e.g. a septum of the cartridge located in the cartridge holder <NUM>.

Additionally, the pen-type injector <NUM> comprises a protective cap <NUM> which is to be releasably arranged on the cartridge holder <NUM>. The protective cap <NUM> comprises a clip <NUM> by way of which the pen-type injector <NUM> with the cap <NUM> mounted thereon can be clipped and fastened to e.g. a piece of cloth, like a pocket of a shirt. The protective cap <NUM> may positively engage with the interface section <NUM> and may further substantially flush with the outer circumference of the body <NUM> of the pen-type injector <NUM> when mounted on the cartridge holder <NUM>.

At its distal end, the protective cap <NUM> comprises a receptacle <NUM> having a substantially flat-shaped or flattened bottom portion <NUM> and a sidewall <NUM>. The sidewall <NUM> as illustrated in <FIG> and <FIG> comprises an inward facing serrated or corrugated surface that mates and corresponds with the geometry and outer circumference of a tamper-evident closure <NUM>, which is separately illustrated in <FIG> and which is initially present at the distal end of the threaded socket <NUM> of the cartridge holder <NUM>.

The tamper-evident closure <NUM> comprises a disc-like shape and features radially outwardly extending lobes <NUM> separated by radially inwardly extending grooves <NUM>. The lobe-groove-structure of the outer circumference of the tamper-evident closure <NUM> strictly mates and corresponds with the radially inward facing geometry and structure of the protective cap <NUM>. This way, when inserting the tamper-evident closure <NUM> in the receptacle <NUM>, a positive engagement of protective cap <NUM> and tamper-evident closure can be provided by way of which an angular momentum between cap <NUM> and tamper-evident closure <NUM> can be transferred for releasing the tamper-evident closure <NUM> from the housing <NUM>, <NUM>.

Claim 1:
A pen-type injector for injecting of a dose of a medicament, comprising a housing (<NUM>, <NUM>) to accommodate a cartridge being at least partially filled with a medicament, wherein the housing (<NUM>, <NUM>) comprises a dispensing end (<NUM>) with an access opening (<NUM>), characterized in that the access opening (<NUM>) is closed by a tamper-evident closure (<NUM>) and wherein the tamper-evident closure (<NUM>) comprises an identification member embedded in the bulk of the closure (<NUM>) or being attached to an outer surface thereof, wherein the identification member enables a user making use of an electronic reading device to identify and to confirm a genuine origin of the pen-type injector.