An injection or infusion device comprising an improved release liner

TECHNICAL FIELD

0001The current invention relates to an injection device that is configured for attachment to the skin of a patient using an adhesive layer, the injection device comprises a release liner covering the adhesive layer. The release liner has an aperture and is strengthened using a strengthening sheet of material. Additionally a method is presented for application of the strengthening sheet to the release liner.

BACKGROUND OF THE INVENTION

0002Injection and infusion devices are used for the subcutaneous delivery of liquid medicaments to a patient. Such injection devices are often pen-shaped, having a long axis and are called injection pens. The injection pens comprise a housing, which can hold a dose setting and dose delivery mechanism. The medication is preferably present in a cartridge or in a prefilled syringe. A cartridge is normally attached to the housing of the injection pen using a cartridge holder. The user sets a dose of medication which is subsequently delivered from the cartridge. Such injection pens are used to deliver separate injections and not intended for continuous delivery of a medicament. The needle is attached to the injection pen each time before use and the needle penetrates a septum that is attached to the cartridge.

0003Infusion devices deliver the medication from the cartridge using a drive mechanism and a control mechanism that controls the advancement of a piston rod that abuts a moveable plunger present in the cartridge containing the medication. The medication is delivered to the patient via a fluid path and an external infusion set comprising a needle for subcutaneous delivery. With such infusion devices both continuous and temporary medicament delivery profiles can be programmed.

0004A patch device is an example of an infusion device that is attachable to the skin of the patient. Such patch devices do not need an external infusion set for delivery as the needle is directly contained in the patch device and may be inserted into the patient therefrom.

0005The injection and infusion devices comprise a dose setting mechanism, a delivery mechanism, a needle insertion and retraction mechanism or a needle shield protection system which is connected or connectable to a drive mechanism. The drive mechanism is driven by a power source which supplies energy to the injection or infusion device for executing tasks such as medication delivery, establishing a connection between the fluid path and the cartridge, needle insertion, needle retraction, advancing and/or retracting a piston rod, signaling to the user that the medication is in progress and/or complete, signaling to the user that the device can be removed, powering a processor unit in the device or establishing a wireless connection for data transmission to an external such as a smart phone. The power source used in such injection or infusion devices can be selected from a wide variety of options such as, but not limiting to, a spring (compression, torsional spring, and leaf spring), an electromotor, a battery, pressurized gas or liquid-hydraulic systems and the like. In the injection and infusion devices, several operations need to be arranged in a certain sequence for a correct operation and transmission of power from the energy source to final medicament delivery, for example, by advancing the plunger in the cartridge.

0006For a patch injection device, the needle must be inserted first, either using a steel needle (also called cannula) or a combination of a steel needle with a soft cannula; subsequently the steel needle must be retracted to leave the soft cannula in the subcutaneous tissue of the patient, followed by delivery of medication. Preferably, the needle, either a soft needle or a steel needle is retracted into the device before the patch device can be removed from the body. Alternatively, the needle is not retracted but a needle shield is extended from the body of the device to protect the needle tip and prevent needle stitching by the patient.

0007The liquid medicament is produced under sterile conditions and enclosed in a container to keep the medicament sterile. Such a container can be the above mentioned cartridge or an ampoule, both of which are preferably made of glass. As an alternative plastic containers may be used. The cartridge comprises a barrel having two openings, one opening at the end of a neck portion and a second opening opposite to the neck portion. The opening at the neck portion is normally closed by a penetrable septum that is attached to the neck portion using a crimp. The opposite opening is closed by a plunger and the medicament is enclosed by the barrel between the septum and the plunger. During medication delivery, the plunger in the cartridge is advanced in the cartridge by the drive mechanism. The cartridge is filled with the liquid medicament in a fill finish line, and either the plunger is inserted first into the barrel and the medicament is filled via the neck portion followed by closure using the septum crimped onto the neck portion, or the septum is attached first to the cartridge's neck and the medicament is filled from the opposite opening and finally closed by the plunger. The fill finish is done in a sterile environment. The filled cartridge is normally subjected to a visual inspection to ensure that no particulates are present in the liquid.

0008The filled cartridge is assembled with an injection or infusion device, preferably a patch device, having a fluid path unit that is used for establishing the connection between a fluid path and the liquid medicament. The fluid path unit comprises a housing or containment for housing a fluid path in the interior. The fluid path may comprise a needle or spike that can pierce through the septum of the cartridge, a tubing for fluid transfer connecting the needle or spike to a second needle (which is either a soft needle and/or a steel needle) intended for penetrating the skin of the patient. Preferably, during shelflife there is no connection between the cartridge and the fluid path and just prior to use the connection is established by penetrating the septum of the cartridge with the spike or needle. The interior of the housing or containment for the fluid path unit is sterilized during manufacturing and remains in a sterile condition during shelflife. The fluid path unit and the cartridge can be assembled in a sterile environment which may be cumbersome (for example in view of the visual inspection) and expensive or it is assembled in a non-sterile environment such as a clean room. The device comprising the assembly of the fluid path unit and cartridge can be in a sterile packaging during the shelflife which is removed just before use or it is in a non-sterile packaging. In either option, a sterile connection needs to be established between the content of the cartridge and the fluid path in the containment of the fluid path unit prior to use and this is usually done in a non-sterile environment.

0009The <patcit id="pcit0001" dnum="US20160199568A"><text>US20160199568</text></patcit> discloses an infusion device with a peristaltic pump. The tubing of the pump is connected to a connector assembly comprising an ampoule with a liquid medicament and a connector for the tubing. Between the ampoule and the connector there are two strips to prevent the liquid passing from the ampoule to the tubing. The ampoule is directly closed by the film and not with a septum, and the connector for the tubing is always connected to the ampoule - there is no spike or needle for establishing the connection between the liquid medicament just prior to use. Removing the strip simultaneously establishes: a) a fluid connection between the cartridge and the tubing, and b) a sterile connection between the ampoule and the tubing. The fact that there is no separate closure for the ampoule reduces the reliability of the fixed connection and cannot be used for a modular assembly approach, moreover it will be cumbersome to use standard fill-finish procedures and standard components (such as a cartridge closed by a septum) for the device described in <patcit id="pcit0002" dnum="US20160199568A"><text>US20160199568</text></patcit>.

0010In <patcit id="pcit0003" dnum="US4019512A"><text>US4019512</text></patcit> a sterile connection between two connector ends of two tubings is established in a non-sterile environment by removing two strips from the two connector ends. The two strips keeping the ends of the tubings in a sterile environment during shelflife and the strips are removed after the two connector ends have been connected. A sterile connection is established between two tubings and not intended or suitable for establishing a connection between a cartridge and a fluid path of an infusion device.

0011In European Patent Application <patcit id="pcit0004" dnum="EP18161873"><text>EP18161873.7</text></patcit> a cartridge is provided that is closed with a septum and therefore steps a) and b) that are mentioned above and occur simultaneously in the prior art are separated from each other. First a sterile connection is established between the fluid path and the standard cartridge and secondly the spike or needle of the fluid path penetrates the septum of the cartridge to establish the fluid connection. The advantage of having a standard cartridge closed by a septum and crimp is that standard production procedures can be used for fill-finish of the cartridge using standard components which increases the reliability of the assembly and the acceptance by pharmaceutical companies. A modular approach can be used, the cartridge may be filled at a different location then the assembly with the fluid path unit. Another advantage is that the cartridge with the sterile surface on the septum can be assembled with the sterile fluid path unit in a non-sterile environment. The connection shown in <patcit id="pcit0005" dnum="US20160199568A"><text>US20160199568</text></patcit> must be assembled in a sterile environment.

0012In European Patent application <patcit id="pcit0006" dnum="EP18161873"><text>EP18161873.7</text></patcit>, the septum of the cartridge is covered by a sterile barrier film and/or a passage inside of the injection device is covered by a sterile barrier film. The films are intended to keep the surface of the septum in a sterile condition and/or to keep a fluid path unit enclosed in a compartment having the passage in a sterile condition. The ends of the films go through a passage in the housing and through a passage in an adhesive layer configured for attaching the device to the skin of the patient. Prior to use, the adhesive layer is covered with a release liner protecting the skin adhesive layer. The ends of the sterile barrier films are connected to the release liner and the two sterile barrier films are removed simultaneously from the septum respectively the passage when removing the release liner from the adhesive layer. For a correct attachment of the ends of the sterile barrier films to the release liner, also a passage or aperture in the release liner is required. The sterile barrier films that are attached to the septum respectively to the passage of the fluid path, need to go through the passages in the housing, the adhesive layer and the release liner before the end of the sterile barrier can be attached to the surface of the release liner. A disadvantage of this approach is that the passage in the release liner weakens the liner as corners of the passage may act as stress concentrators upon liner removal. This may lead to tear damage or in the worst case only partial removal of the release liner being a discomfort to the patient and potentially prevents the attachment of the device to the patients skin.

0013It is an object of the present invention to overcome the above mentioned drawbacks for an injection device that is configured for attachment to the skin of a patient and improve the usability of the device and the reliability of the release liner removal while simultaneously removing one or two sterile barrier films that are connected to the inside of the injection device. It is a further object of the present invention to remove one or two sterile barrier films that are removably connected to the inside of the injection device and additionally remove a further sterile barrier film connected to the outside of the housing of the injection device during removal of the release liner.

0014These objectives are solved by covering the release liner with a strengthening sheet that adhesively connects to both the surface of the release liner as well as to an end of the sterile barrier film. The strengthening sheet covers and strengthens the aperture in the release liner. This objective is further solved by covering two ends of two sterile barrier films that are removably attached to an inside surface within the device, one film being attached to the passage of the fluid path whereas the other film is removably connected to the cartridge and covering the septum. A further objective is solved by attaching the strengthening sheet to the ends of the sterile barrier films that are releasably connected to the inside of the device and attaching the strengthening sheet to the further sterile barrier film connected to the outside housing of the injection device.

DEFINITIONS

0015The term "medicament" or "medication" includes any flowable medical formulation suitable for controlled administration through a means such as, for example, a cannula or a hollow needle and comprises a liquid, a solution, a gel or a fine suspension containing one or more medical active ingredients. A medicament can be a composition comprising a single active ingredient or a pre-mixed or co-formulated composition with more than one active ingredient present in a single container. Medication includes drugs such as peptides (e.g., insulin, insulin-containing drugs, GLP-1 containing drugs or derived or analogous preparations), proteins and hormones, active ingredients derived from -or harvested by- biological sources, active ingredients based on hormones or genes, nutritional formulations, enzymes and other substances in both solid (suspended) or liquid form but also polysaccharides, vaccines, DNA, RNA, oligonucleotides, antibodies or parts of antibodies but also appropriate basic, auxiliary and carrier substances.

0016The distal end or distal direction is defined by the direction of the needle configured to penetrate the skin of the patient. For an injection pen this may be the injection needle and the end of the pen holding the needle or being configured to hold the needle is the distal end. For an infusion device the distal end and the distal direction is towards the needle configured to penetrate the skin of the patient, which may be along the axis of the device or tilted or perpendicular to the axis of the device. The distal direction in an infusion device represents the direction in which the medicament flows towards the insertion needle. The proximal direction or end is opposite to the distal direction or end.

0017In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. For example, "a first film" does not exclude the fact that there may be two films that functionally or structurally fulfill the purpose of "a first film". The mere fact that certain elements or steps are recited in distinct claims shall not preclude the existence of further meaningful combinations of these elements or steps.

GENERAL DESCRIPTION OF THE INVENTION

0018It is an objective of the present invention to provide an injection device which is configured for attachment to the skin of a patient using an adhesive layer. The adhesive layer is preferably directly attached to the outside surface, for example to the housing of the injection device. The injection device comprises a release liner that covers the adhesive layer and thereby prevents undesired attachment of the injection device to the skin of the patient. The release liner comprises a sheet of material wherein a first surface of the sheet contacts the adhesive layer. The first surface of the sheet preferably entirely covers the adhesive layer such that the sticky surface is covered by a non-sticky sheet of material. The release liner further comprises an aperture which defines a passage for a film that is connected to a first sterile barrier film which is located within the injection device, preferably within the housing of the injection device. The first sterile barrier film preferably passes through an aperture present in the injection device, preferably through an aperture within the housing or through an aperture connecting the inside of the housing to the outside of the housing. An end of the first sterile barrier film is connected to a second surface of the sheet of material that is opposite to the first surface, i.e. the surface that is not contacting the adhesive layer. The release liner is covered by a strengthening sheet which is adhesively connected to the second surface of the sheet of material and covering the aperture in the release liner and the end of the film. The end of the film is connected to the sheet of material forming the release liner, such that the end of the film and therewith also the first sterile barrier film connected thereto can be removed together with the release liner when the liner is removed. This facilitates the formation of a sterile connection within the injection device upon use while keeping the material behind the sterile barrier film in a sterile condition during shelf-life. Preferably, the end of the sterile film needs to pass through the release liner for attachment to the second surface such that an aperture in the sheet of material is required. Upon release of the release liner, the user pulls on the release liner and will pull also on the end of the first sterile barrier film, requiring and additional force leading to local stress concentrations around the aperture in the sheet of material, for example in the corners of the aperture. These stress concentrations may be above the tear strength of the sheet of material and lead to local disruption or tearing of the release liner. For example, the release liner can only be partially removed which is not desired as it reduces the reliability of the device during use as proper skin attachment is prevented or increases user complaints as the device cannot be operated. Therefore, the strengthening sheet is adhesively attached to the release liner covering at least the aperture in the sheet of material and thereby strengthening the release liner, thus preventing fracture due to local stresses around the aperture. Additionally, the end of the first sterile barrier film is preferably covered by the strengthening sheet as well and thereby strengthens the link between the end of the first sterile barrier film and the release liner, ensuring a safe removal of an intact release liner including the end of the film and the first sterile barrier film connected thereto.

0019The injection device may have one first sterile barrier film or may have a plurality of first sterile barrier films, each connected to a surface of the inside of the housing. One end of at least one sterile barrier film is connected to the second surface of the sheet of material forming the release liner. The end of a second or third first sterile barrier film may be connected to the second surface of the sheet of material as well. The strengthening sheet of material covers and attaches to one end of at least one first sterile barrier film, however the strengthening sheet may cover the plurality of ends of the plurality of first sterile barrier films.

0020Preferably the release liner further comprises a second aperture for a hollow needle wherein the end of the hollow needle is configured to be moved from a first position within the injection device to a second position outside the injection device, the second aperture for the hollow needle being covered by a removable second sterile barrier film that is adhesively attached to the strengthening sheet. The second sterile barrier is connected to the strengthening sheet and thus results in removal of the second sterile barrier together with the first sterile film when the release liner is removed. Preferably the second sterile barrier film is not connected or attached to the sheet of material forming the release liner. The effect is that when users remove the release liner then the first and second sterile barrier films are removed simultaneously in a single step and that a sterile connection is established within the device and the insertion needle is uncovered and free for insertion into the skin of the patient and can move from the inside to the outside of the device without penetrating the second sterile barrier film. This increases the usability of the device for the patient as only a single step is required, namely liner removal.

0021The first sterile barrier film forms a removable sterile barrier within the injection device covering a passage or an aperture that is located inside of the injection device or inside of the housing that is part of, and encloses the injection device. Preferably, the removable sterile barrier film has edges or edge regions that are attached to a housing or a housing part inside the device wherein the passage is located within the housing or housing part. The edges or edge regions may be attached to the housing section adjacent to the passage or aperture. The attachment or connection between the sterile barrier film and the housing section has a strength, preferably shear strength or peel-off strength, which is below the tear or tensile strength of the sterile barrier film such that the connection between the edges of the film and the housing section adjacent of the passage fails when the release liner is removed. Alternatively, the sterile barrier film or the housing section adjacent from the passage has a locally reduced strength such that either the sterile barrier film or the housing section fails in a controlled manner when the release liner is removed. A removable first sterile barrier film ensures that the film can be removed to open the passage such that, for example, a needle can pass through the passage without penetrating the barrier film having the risk of needle blockage and particulate formation which decreases the reliability of the device.

0022The passage or aperture on the inside of the injection device may be part of a sterile containment enclosing a fluid path comprising a spike or hollow needle configured to be moved within the injection device through the passage into a septum of a cartridge. The sterile containment may be part of the housing or a housing part of the injection device and the passage or aperture is part of a wall section of the housing or housing part. The passage or aperture is preferably oriented perpendicular to the planes forming the first and second surfaces of the release liner when the release liner is attached to the adhesive layer, i.e. preferably perpendicular to a bottom surface of the housing intended to be placed onto the patient's skin. The passage is open when the sterile barrier film is removed and the passage is available for the spike to move through the passage and establish a fluid path connection to the medicament in the cartridge. The spike or hollow needle is driven by an insertion mechanism that is preferably driven by a spring and the spike or hollow needle preferably moves parallel to the plane of the first and second surfaces of the release liner when attached.

0023The injection device wherein the first sterile barrier film forms a removable sterile barrier within the injection device covering a septum of a cartridge and keeping a surface of the septum in a sterile condition. The surface that is kept in a sterile condition is opposite to the septum's surface contacting the liquid medicament. The injection device may comprise a first sterile barrier film covering a passage or aperture of a sterile compartment with a fluid path as described above and a second first sterile barrier film that covers the septum of the cartridge. It may be envisages that more than two first sterile barrier films are removably attached within the injection device. The first sterile barrier covering the septum of the cartridge keeps the septum in a sterile condition during shelflife. The septum covered by the first sterile barrier film is preferably sterilized as a unit and the barrier film prevents contamination during shelflife. Just before use, the first sterile barrier films covering the septum and the passage are removed to form a sterile connection between the needle (or spike) and the liquid medicament, thus preventing contamination when the fluid path connection is established upon needle (or spike) insertion through the septum.

0024The film may be an integral part of the first sterile barrier film, or the film is separate from and connected to the first sterile barrier film forming a pull tab for the first sterile barrier film. When the film is separate from the first sterile barrier film then it may be glued, heat-welded, ultra-sonic welded or attached to the sterile barrier film using a bracket or a clip. The pull tab may be integrated with the sterile barrier film, for example both are made from Tyvek or another porous film such as paper allowing for gas plasma or ethylene oxide sterilization. Alternatively, a separate pull tab is attached to the sterile barrier film and made from a non-porous polymer film such as PET, PBT, PE, PP or the like. Alternatively paper or reinforced or laminated paper may be used. The pull tab may be made from a film having a higher bending resistance compared to the first sterile barrier film as it may be folded within the device. For example, an elastomeric material may be used.

0025The end of the film or the end of the pull tab that is connected to the first barrier film is adhesively connected or welded to the second surface of the release liner. The end of the film is arranged through the passage in the release liner prior to connecting to the second surface of the liner. Subsequently the connection of the end of the film or pull tab to the second surface is reinforced using the strengthening sheet. The strengthening sheet preferably is an adhesive film having an adhesive layer covering the passage in the release liner and the at least one end of the film. A robust connection between the end of the film and the release liner is established ensuring that upon removal of the liner also the end and the removable sterile barrier can be removed from the device in a single step.

0026The injection device wherein the strengthening film covers and adhesively connects to the end of the film of the first sterile barrier film covering the passage of the sterile containment enclosing the fluid path and/or the strengthening film covers and adhesively connects to the end of the film of the first sterile barrier film covering the septum of the cartridge. Thus, either one or both ends are covered by the strengthening sheet of material. Alternatively, two separate strengthening sheets may be applied for each end of both first sterile barrier films. At least one of the two strengthening sheets covers the second aperture for a hollow needle. The strengthening sheet ensures that at least one first sterile barrier film and the removable second sterile barrier film covering the second aperture in the housing are simultaneously removed upon release liner removal.

0027In a preferred embodiment, the strengthening film covers the second sterile barrier film and the end of the film of the first sterile barrier film covering the passage of the sterile containment enclosing the fluid path. The strengthening sheet covers the second sterile barrier film (covering the hollow insertion needle) and the end of the film covering the fluid path containment. This facilitates that the strengthening sheet is adhered to the end of the first sterile barrier film covering the fluid path unit and this strengthening sheet can be mounted and adhered to the second surface of the sheet forming the release liner before the cartridge with the sterile barrier film is mounted in a separate step and possibly at a different time or geographic location. The cartridge is inserted in a separate step and the septum of the cartridge may be covered by a first sterile barrier film. The end of the sterile barrier film covering the septum may be adhered to the second surface of the release liner using a second strengthening sheet or a part of the first strengthening sheet that has not been used yet.

0028The release liner having two strengthening films adhesively attached to the second surface of the sheet of material forming the release liner wherein one of the two strengthening films covers and adhesively connects to the second sterile barrier film and the end of the film of the first sterile barrier film covering the passage for the sterile containment enclosing the fluid path.

0029The release liner may comprise a conductive layer, for example a silver ink layer, carbon black layer, covering and being part of a signaling sensor, for example a capacitive sensor. The conductive layer may for example electrically shield a part of the capacitive sensor. The conductive layer may be part of, or coated onto the sheet of material forming the release liner or may be part of the sheet of material that strengthens the release liner. The conductive layer may be, for example, applied on the sheet of material and/or onto the strengthening sheet using metal vacuum deposition techniques or printing techniques. The metal may be selected from silver, gold or aluminium. Also, a carbon layer may be deposited onto the surface using vacuum deposition or printing techniques. Alternatively, the release liner is made from a conductive material such as a sheet of aluminium or a carbon filled plastic material wherein the carbon particles form a percolating network. The conductive layer may be a continuous layer covering the whole release liner or it may be partially covering the release liner. The conductive layer effects electrical shielding of the sensor when the release liner is attached to the device and removal of the liner causes a change in capacitance measured by the sensor and which can be used to detect proper removal of the release liner by enabling electrical signalling to a control unit in the device.

0030The injection device comprises a housing enclosing a fluid path present in a containment and the fluid path comprises a spike for penetrating the septum of the cartridge connected by a tube to a hollow needle for penetrating the skin of a patient. The containment comprises the passage covered by the removable first sterile film. The fluid path containment enclosed by the housing is preferably sterilized while the first removable sterile barrier film is attached to, and covering the passage. For example, the first sterile barrier film is made of a porous membrane such as Tyvek, and the fluid path containment is sterilized using gas plasma or ethylene oxide gas sterilization. Alternatively, radiation sterilization techniques may be used such as gamma-radiation, e-beam or X-rays. The housing enclosing the fluid path containment preferably comprises the second aperture for the hollow needle that is intended for penetrating the skin of the patient. The housing enclosing the fluid path containment may form the main housing, i.e. outer housing of the injection device or it may be an internal housing part. In the latter case at least one outer housing encloses the housing for the fluid path containment. Each of the housing or housing parts has a passage for the film that is connected to the release liner and the housing or housing parts are configured to guide the film, for example around rounded edges surrounding the passages, pins or protrusions present in the housing to allow for a smooth removal of the film and the first sterile barrier film connected thereto.

0031The injection device comprises an outer housing enclosing inner housing parts such as the housing for the fluid path containment. The outer housing comprises an outer surface configured for application of the skin adhesive layer. The outer housing supports subassemblies present in the housing such as the drive mechanism, a control mechanism for controlling the device, and a needle insertion and retraction mechanism. The outer housing may have a cover or closure cap that can be removed for insertion of a cartridge followed by closing the housing using the cover or cap. Such a closure cover or cap may comprise a viewing window for viewing the cartridge and the progress of the injection.

0032The injection device comprises a cartridge holder for holding a cartridge comprising a fluid medicament sealed in a barrel by a moveable plunger and a pierceable septum covered by the removable first sterile barrier film. The cartridge holder may be part of an internal housing component, for example the housing forming the sterile containment for the fluid path, or it may be part of an internal housing holding the drive mechanism. Optionally there may be a separate housing part dedicated to receive the cartridge and that is connectable to the outer housing.

0033The skin adhesive layer is connected to an outside surface of the housing and may comprise a skin adhesive for adhesion to the skin, a circuit layer comprising an electrically conductive sensor and an adhesive layer for adhesion to the outside surface of the housing. Preferably, the electrically conductive sensor of the adhesive layer is at least partially covered by the conductive layer of the release liner when the release liner is attached to the adhesive layer.

0034A method for assembling an injection or infusion device that can be attached to the skin using an adhesive layer which is covered by a release liner prior to use. The method comprises the steps of: <ul id="ul0001" list-style="dash" compact="compact"><li>Providing a housing assembly comprising a fluid path comprising a spike that is configured to penetrate the septum and a needle that is configured for insertion into the skin of the patient. The fluid path is enclosed in a housing part or fluid path containment having a passage that is covered by a second sterile barrier film thereby keeping the fluid path in a sterile condition,</li><li>Guiding an end of the second sterile barrier film through a passage in the housing, the adhesive layer and the release liner,</li><li>Attaching the end of the second sterile barrier film to the outside surface of the release liner that is not in contact with the skin adhesive layer,</li><li>Providing a cartridge filled with a medicament and closed with a septum that is attached to the cartridge using a crimp. The surface of the septum is covered by a first sterile barrier film that is connected to the crimp thus keeping the surface of the septum in a sterile condition. The sterile barrier film comprises an end which ensures that the first sterile barrier film can be removed from the crimp,</li><li>Insertion of the cartridge into a cartridge holder that is part of the injection device, the cartridge is inserted such that the end of the first sterile barrier film of the cartridge is guided through a passage in the housing, the adhesive layer and the release liner,</li><li>Attaching the end of the first sterile barrier film to the outside surface of the release liner that is not in contact with the skin adhesive layer,</li><li>Applying an adhesive sheet of material onto the outside surface of the release liner, thereby at least covering both ends of the first and second sterile barrier films and the passage in the release liner,</li><li>Optionally, a second sheet of strengthening material is attached to the outside surface of the release liner before cartridge insertion.</li><li>As another option the first sterile barrier film covering the septum is extended by connecting a pull tab thereto which may be made from a different material then the first sterile barrier film. The pull tab is attached to the first sterile barrier film prior to the cartridge insertion step</li><li>As a further option, a flip off cap covering the first sterile barrier film and/or the pull tab is attached to the crimp, the flip off-cap is at least partially removed before insertion of the cartridge into the cartridge holder.</li></ul>

LEGENDS TO THE FIGURES

0035While the invention has been described in detail in the drawings below and foregoing general description, such description is to be considered illustrative or exemplary and not restrictive. Variations to the disclosed embodiments can be understood and effected by those skilled in the art and practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. <ul id="ul0002" list-style="none" compact="compact"><li><figref idref="f0001">Figure 1</figref>: Cartridge closed by a septum with a crimp, the first sterile barrier film is connected to the crimp thereby covering the septum. The free end of the film is an integral part of the first barrier film.</li><li><figref idref="f0001">Figure 2</figref>: Cartridge closed by a septum with a crimp, the first sterile barrier film is connected to the crimp thereby covering the septum. The film is a separate film forming a pull tab and is connected to the first barrier film.</li><li><figref idref="f0002">Figure 3</figref>: Longitudinal section of an injection device showing the cartridge with a septum covered by a removable barrier film and a passage for a sterile compartment enclosing a spike that is covered by a removable barrier film as well. The ends of the films are connected to the outer surface of the release liner.</li><li><figref idref="f0002">Figure 4</figref>: Detailed view of the assembly of the cartridge and the fluid path unit of <figref idref="f0001">Figure 2</figref> when the release liner is removed.</li><li><figref idref="f0003">Figure 5</figref>: Injection device during assembly, the end of the film connected to the second sterile barrier film covering the passage of the fluid path containment passes through the apertures in the housing and the release liner.</li><li><figref idref="f0003">Figure 6</figref>: Injection device during assembly, the end of the film shown in <figref idref="f0003">Figure 5</figref> is attached to the outside surface of the release liner.</li><li><figref idref="f0004">Figure 7</figref>: Injection device during assembly, the cartridge with a sterile barrier film covering the septum (<figref idref="f0001">Figures 1 and 2</figref>) has been inserted into the cartridge holder. The end of the film passes through the apertures in the housing and the release liner.</li><li><figref idref="f0004">Figure 8</figref>: Injection device according to <figref idref="f0004">Figure 7</figref> during assembly, the end of the film covering the septum is attached to the outside surface of the release liner.</li><li><figref idref="f0005">Figure 9</figref>: Injection device whereby an additional strengthening sheet has been adhesively attached to outside surface of the release liner thereby covering the ends of the sterile barrier films that are connected to the passage of the fluid path compartment and cartridge respectively. Additionally, the strengthening sheet is attached to a third sterile barrier film covering the insertion needle.</li><li><figref idref="f0005">Figure 10</figref>: Injection device with two strengthening sheets of material attached to the outside surface of the release liner, a first sheet covers the end of the second sterile barrier film that covers the passage of the fluid path compartment and the third sterile barrier film covering the insertion needle. The second strengthening sheet covers both ends of the first and second sterile barrier films.</li><li><figref idref="f0005">Figure 11</figref>: Injection device with two strengthening sheets of material attached to the outside surface of the release liner, a first sheet covers both ends of the first and second sterile barrier film and a second sheet covers the third sterile barrier film.</li></ul>

DETAILED DESCRIPTION OF THE FIGURES

0036In <figref idref="f0001">Figure 1</figref>, a cartridge (9) is shown comprising a barrel (1), preferably made of glass and optionally made from a polymeric material such as polypropylene or cyclo-olefinic polymer (or copolymer). The barrel (1) is preferably cylindrically shaped having a narrowed neck (2) closed by a not shown septum that is connected to the cartridge (9) using a crimp (3). The crimp (3) has a not shown opening surrounding the not shown septum. A first film (5), which preferably is a flexible film, has been removably attached to the crimp using a first sterile barrier film section (4). An end (6) of the first film (5) is not attached to the crimp and available for attachment to a release liner of the device or to a connector film as will be discussed below. <figref idref="f0001">Figure 2</figref> shows a variant where the end (6) of the film is attached to a connector film (7) that is separate from the first film (5). The first film (5) has a U-shaped fold (8) and the connector film (7) is sandwiched between the first sterile barrier film (4) and the end (6). The connector film (7) has been attached to the first film (5) using adequate attachment means such as glueing or welding. The connector film (7) has a pull tab (10) intended for connecting to the release liner. Preferably, the first barrier film (4) is a porous film that enables gas sterilization such as gas plasma (hydrogen peroxide) or ethylene oxide sterilization (ETO) to sterilize the septum of the cartridge. Examples are non-woven porous polyethylene or polypropylene films or paper (cellulose) films that may be laminated or coated to enhance or control the adhesive properties.

0037<figref idref="f0002">Figure 3</figref> shows a longitudinal section of an injection device (16) showing an assembly of the cartridge (9) inserted into the injection device (16). The injection device (16) may be attached to the skin of the patient using a skin adhesive layer (21) which is covered by a release liner (20). <figref idref="f0002">Figure 4</figref> shows a detail when the first film and a second film (5, 11) have been removed together with the release liner (20). The function of the second film (11) will be discussed below. In <figref idref="f0002">Figure 4</figref>, the cartridge (9) is shown with a moveable plunger (26) that can move towards the septum (27) for expelling the medicament. The external housing (17) encloses both the cartridge (9) and a housing (13) for the fluid path enclosing a spike (14) that is aligned parallel to the longitudinal axis of the cartridge (9). The first and second films (5, 11) are positioned between the spike (14) and the cartridge (9). The cartridge is positioned within a cartridge holder (15) which, for this example, is part of the housing (13) for the fluid path. The cartridge (9) is axially fixated in the housing (17) and biased towards the housing (13) of the fluid path using a ratchet system (18, 19). A ratchet member (18) may be guided in the housing (17) and axially slided after the cartridge (9) has been inserted such that ratchet teeth of the ratchet member (18) engage ratchet teeth of a counter ratchet member (19) that is axially fixed with respect to the housing (17). The ratchet member (18) engages a proximal rim of the barrel of the cartridge (9) thereby enabling axial fixation of the cartridge in the housing (17) and biasing the cartridge (9) towards the housing (13) of the fluid path. Alternatively, and instead of the ratchet member the cartridge is fixated using a ridge or fin on a not shown cover that may close the housing and during closing the rip or fin is plastically deformed on the proximal rim of the cartridge thereby fixating the cartridge. The first film (5) is connected to the crimp (3) of the cartridge which fixates a septum (27) to the neck (2). The first sterile barrier film (4) is an integral part of the first film (5) is connected to the crimp (3) using a first member (22). The first member (22) may be for example a glue or a double-sided adhesive tape. Optionally the first member (22) is a resilient member such as an O-ring, which may be compressed once the cartridge (9) is fixated using the ratchet system (18, 19). The first sterile barrier film (4) may also be directly heat-welded onto a distal end surface of the crimp (3). The first sterile barrier film (4) is connected to the crimp such that this connection can be released by applying a force to the end (6) of the first film to peel-off the first sterile barrier film (4) from the crimp (3).

0038The housing for the fluid path (13) comprises a passage (25) which allows the spike (14) to move through the passage (25). The passage (25) is covered by a second film (11) and the second barrier film (11a) which is an integral part of the second film (11) is attached to a wall of the fluid path housing (13) and covering the passage (25), thereby preventing contamination of the fluid path comprising the spike (14). Preferably, the second barrier film (11a) is a porous film that enables gas sterilization such as gas plasma (hydrogen peroxide) or ethylene oxide sterilization (ETO) to sterilize the fluid path. The second sterile barrier film (11a) is connected to the fluid path housing (13) using a second member (23). The second member (23) may be for example a glue or a double-sided adhesive tape. Optionally the second member (23) is a resilient member such as an O-ring which may be compressed once the cartridge (9) is fixated using the ratchet system (18, 19). The second sterile barrier film (11a) may also be directly heat welded onto the wall of the housing (13) comprising the passage (25). The second sterile barrier film (11a) is connected to the housing (13) such that this connection can be released by applying a force to the end (12) of the second film (11) to peel-off the second sterile barrier film (11a) from the housing (13) such that the passage (25) is free for the spike to move through.

0039The first and second films (5, 11) are guided through an aperture (24) present in the cartridge holder (15) such that the ends of the first and second films (6, 12) can be guided through an aperture (28) in the release liner (20).

0040The ends of the films (6, 12) are connected to the outer surface of the release liner (20) such that the first and second films (5, 11) are removed from the crimp (3) respectively passage (25) upon removal of the release liner (20) from the skin adhesive layer (21), see <figref idref="f0002">Figure 4</figref>. Optionally, the gap that may exist between the septum (27) and the wall of the fluid path housing (13) after removing the first and second films (5, 11) is closed due to the resilience of the connecting members (22, 23) and/or due to the ratchet system (18, 19) which immediately closes the gap. A disadvantage of the assembly shown in <figref idref="f0002">Figures 3 and 4</figref> is that the aperture (28) in the release liner (20) acts as a stress concentrator such that the release liner can easily tear leading to partial removal of the release liner (20). As a consequence, the device cannot be properly attached to the skin of the patient.

0041An embodiment according to the present invention is shown in <figref idref="f0003 f0004 f0005">Figures 5 to 9</figref>. The injection device (16) is shown upside down with the release liner (20) covering the skin adhesive layer. The release liner (20) has a cut-out (29) acting as a handle to facilitate the removal of the release liner (20). The release liner (20) has an aperture (28) which is C-shaped and starting at the rim of the release liner (20) to facilitate the insertion of the second film (11) from the side using the end (12). The outside surface of the release liner (20), i.e. the surface that is not contacting the skin adhesive, comprises a second adhesive spot (31) which may be a double sided adhesive tape. The end of the second film (12) is attached to the outside surface of the release liner (20) using the second adhesive spot (31), see <figref idref="f0003">Figure 6</figref>. Alternatively, the second adhesive spot (31) is present at the end (12) of the second film (11). Other attachment means for the end (12) of the second film (11) are, for example, heat welding or ultrasonic welding. The surfaces that need to be contacted to each other may be roughnened, etched, blasted, heat treated or plasma treated to enhance the adhesive connection there between. Once the end of the second film (12) has been attached to the release liner (20), the cartridge (9) is preferably inserted sideways into the cartridge holder (15), see <figref idref="f0004">Figure 7</figref>. The end (6) of the first film (5) or the pull tab (10) of the connector film (7) are guided into the C-shaped aperture (28) during cartridge insertion and the first and second films (5,11) may be arranged parallel to another and contact each other. The end of the first film (6) or the pull tab (7) is attached to the release liner using a first adhesive spot (30), see <figref idref="f0004">Figure 8</figref>. The options presented above for attaching the second film (11) to the second adhesive spot (31) equally apply to attachment of the first film (5) to the first adhesive sport (30).

0042The sequence presented in <figref idref="f0003 f0004">Figures 5 to 8</figref> may also be reversed, i.e. the cartridge (9) may be inserted and the first film (5) is attached to the release liner (20) followed by attaching the second film (11) to the release liner.

0043The release liner (20) comprises a second aperture (32) that surrounds a third sterile barrier film (33), <figref idref="f0004">Figure 8</figref>. The third sterile barrier film (33) is removably connected to the housing (17) of the injection device or to the housing (13) of the fluid path containment. The third sterile barrier film (33) covers a passage in the housing that is available for a hollow needle to move from a first position in the injection device to a second position outside the injection device for penetrating the skin of the patient. The hollow needle preferably moves perpendicular to the plane of the release liner (20). The third sterile barrier film (33) is preferably made from the same material as the first and second sterile barrier films (4,11a) and allows for gaseous sterilization techniques. The release liner (20) is preferably not directly connected to the third sterile barrier film (33) but surrounds it.

0044A strengthening sheet (40) is attached to the release liner (20) and thereby covering at least the end (6) of the first film (5), the end (12) of the second film (11), the third sterile film (33) and the aperture (28) of the release liner (<figref idref="f0005">Figure 9</figref>). The strengthening sheet (40) is preferably adhesively attached to the surface of the release liner and the surfaces of the first and second films (5, 11) and the third sterile barrier film (33). The strengthening sheet (40) may be made from a polymeric material, a sheet of paper or from a woven or non-woven textile material. Examples for the polymeric sheet materials are: polyethylene terephthalate, polybutylene terephthalate, polyester foils, captam foils or polyolefin films such as HDPE or PP films. The strengthening sheet (40) strengthens the assembly (20, 40) of both sheets thereby preventing mechanical damage to the release liner (20) as the removal of the first and second films (5,11) from the inside of the housing (thereby releasing the connections between the first and second films (5,11) from the septum (3) , respectively aperture (25)) may lead to stress concentrations around the aperture (28) in the release liner (20).

0045A second embodiment is presented in <figref idref="f0005">Figure 10</figref>, the second embodiment differs from the first embodiment in that the strengthening sheet (40) covers the third sterile barrier film (33), the second film (11) and the aperture (28) in the release liner. Thus the second film (11) with the second sterile barrier film (11a) connected to the compartment (13) enclosing the fluid path and the third barrier film (33) are first adhesively connected to the strengthening sheet (40) which may be followed by insertion of the cartridge (9) having the first film (5) connected thereto. The end of the first film (6) or the pull tab (10) may be attached to the release liner (20) after application of the strengthening sheet (40). A second strengthening sheet (41) may be finally applied to the first film (5) to strengthen the connection between the first film (5) and the release liner (20). The second strengthening sheet (41) may partially overlap with the strengthening sheet (40) as shown in <figref idref="f0005">Figure 10</figref>.

0046A third embodiment is shown in <figref idref="f0005">Figure 11</figref>. The strengthening sheet (40) is applied to the first and second films (5, 11) and covers the aperture (28). The second strengthening sheet (41) covers and adhesively connects to the third sterile barrier film (33).

0047Alternative embodiments can easily derived based on the three embodiments described above. For example, it can be envisaged that only the second film (11) is used in the device, keeping the fluid path containment (13) in a sterile condition whereas no first film (5) is used that covers the septum of the cartridge. Thus, only the second film (11) and the third sterile barrier film (33) are covered by the strengthening sheet (40) Alternatively, only a first film (5) is used and no second film (11).

0048In yet another alternative, guide pulleys are used within the device to guide the first film (5) and/or the second film (11) such that the forces required to remove the first and second barrier films (4, 11a) are reduced to facilitate the release liner (20) removal. Such a guide pulley system may be combined with the application of a strengthening sheet (40) to the release liner.

0049In yet another alternative, the injection device comprises a cartridge without a first sterile barrier film whereas the fluid path compartment (13) is provided with a second film (11). The second film may be removed when the release liner is removed, but optionally the second film (11) is not removed and the spike (14) pierces the second sterile barrier film (11a) before piercing the septum of the cartridge upon device activation.

0050In yet another alternative, only a first film (5) is provided covering the septum of the cartridge whereas no second film (11) is applied to the housing of the fluid path compartment (13). The first film (5) may be removed upon removal of the release liner, but alternatively the spike will pierce through the first film and the septum when the first film is not removed. <tables id="tabl0001" num="0001"><table frame="none"><title>PART ANNOTATION</title><tgroup cols="4" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="11mm" /><colspec colnum="2" colname="col2" colwidth="52mm" /><colspec colnum="3" colname="col3" colwidth="15mm" /><colspec colnum="4" colname="col4" colwidth="56mm" /><tbody><row><entry>1</entry><entry>Barrel</entry><entry>19</entry><entry>Ratchet counter member on housing</entry></row><row><entry>2</entry><entry>Neck</entry><entry>20</entry><entry>Release liner, sheet of material</entry></row><row><entry>3</entry><entry>Crimp</entry><entry>21</entry><entry>Skin adhesive, adhesive layer</entry></row><row><entry>4</entry><entry>First sterile barrier film</entry><entry>22</entry><entry>First member</entry></row><row><entry>5</entry><entry>First film</entry><entry>23</entry><entry>Second member</entry></row><row><entry>6</entry><entry>End of first film</entry><entry>24</entry><entry>Aperture cartridge holder</entry></row><row><entry>7</entry><entry>Connector film</entry><entry>25</entry><entry>Passage fluid path containment</entry></row><row><entry>8</entry><entry>U-shaped fold</entry><entry>26</entry><entry>Plunger</entry></row><row><entry>9</entry><entry>Cartridge</entry><entry>27</entry><entry>Septum</entry></row><row><entry>10</entry><entry>Pull tab</entry><entry>28</entry><entry>Aperture release liner, first aperture</entry></row><row><entry>11</entry><entry>Second film</entry><entry>29</entry><entry>Cut out release liner</entry></row><row><entry>11a</entry><entry>Second sterile barrier film</entry><entry>30</entry><entry>First adhesive spot</entry></row><row><entry>12</entry><entry>End of second film</entry><entry>31</entry><entry>Second adhesive spot</entry></row><row><entry>13</entry><entry>Compartment, housing of fluid path</entry><entry>32</entry><entry>Second aperture release liner</entry></row><row><entry>14</entry><entry>Spike</entry><entry>33</entry><entry>Third sterile barrier film</entry></row><row><entry>15</entry><entry>Cartridge holder</entry><entry>40</entry><entry>Strengthening sheet</entry></row><row><entry>16</entry><entry>Injection device</entry><entry>41</entry><entry>Second strengthening sheet</entry></row><row><entry>17</entry><entry>External housing</entry><entry>18, 19</entry><entry>Ratchet system</entry></row><row><entry>18</entry><entry>Ratchet member</entry><entry /><entry /></row></tbody></tgroup></table></tables>