Patent Description:
Drug delivery devices in the form of a patch device for mounting on a patient's skin for subcutaneous delivery of liquid drug are known. Some devices typically receive a cartridge or have an internal reservoir that is filled by the patient / healthcare professional. In this case, the drug is drawn from a vial and transferred into the internal reservoir using a syringe. Since cartridges are widespread and their handling is so much easier, it is advantageous to provide a device that can be employed with standard cartridges. The liquid drug may for instance be a biological medical product or other drugs that are administered merely for single shot administration, within a rather short time depending on the intended use. It is known to provide drug delivery devices in the form of a patch device with a single use disposable component assembled to a reusable component containing drive and control electronics, or as a single disposable component.

The reliability, safety, compactness and ease of use of drug delivery devices worn by a patient is important. For disposable components, the amount of parts and consequently cost of the disposable device is also an important consideration.

In order to satisfy safety and reliability requirements, many conventional patch pump drug delivery devices have complex pump mechanisms and are rather bulky. Also, a long shelf life and adequate sterilization is often difficult to achieve and raises manufacturing costs.

For safety of use of the drug delivery device, it is also important to ensure that it may only be actuated when attached to a patient's skin, and that it remains sterile until administration of the drug.

Gas driven pump systems are known for instance <CIT> discloses a pen-like syringe with a plunger driven prnematically, <CIT> discloses a drug delivery device with an electro-osmotic pump, and <CIT> describes a pneumatic syringe system for processing small volumes of cellular suspensions.

In view of the foregoing, it is an object of the invention to provide a drug delivery device, in particular in the form of a patch device, with a disposable unit, or as an entirely disposable device, for administration of a liquid drug that is safe, reliable, and compact.

It is advantageous to provide a drug delivery device that may be used for administration of liquid drugs provided in a drug container with a plunger.

It is advantageous to provide a drug delivery device that is easy to use.

It is advantageous to provide a drug delivery device that is economical to produce.

It is advantageous to provide a drug delivery device that has a long shelf life.

Objects of the invention have been achieved by providing the drug delivery device according to claim1. Dependent claims set forth various advantageous embodiments of the invention.

Disclosed herein, according to a first aspect of the invention, is a drug delivery device comprising a delivery unit including a drug container, a liquid flow system, a pumping system, and a casing enclosing therein the drug container, the pumping system and at least a part of the liquid flow system. The drug container comprises a barrel portion and a plunger slidably mounted within the barrel portion and sealing the drug within the container at one end of the barrel portion, the liquid flow system connected fluidically to the drug container during delivery of the liquid drug. The drug container is contained in a hermetic manner within a container receiving cavity of a container casing portion of the casing and the container receiving cavity is fluidically interconnected to a fluid outlet of the pumping system in a gas tight manner. The pumping system comprises a fluid inlet connected to environmental air, the pumping system configured to pump environmental air drawn in through the fluid inlet into the container receiving cavity generating a gas pressure within the container casing thus applying pressure on a back end of the plunger for delivery of the liquid drug.

In an advantageous embodiment, the pumping system comprises a pump engine including.

In an advantageous embodiment, the drug container is a drug cartridge comprising a septum at one end.

Disclosed herein, according to a second aspect, is a drug delivery device comprising:.

In an embodiment, the delivery unit comprises a casing including a container casing portion comprising a plunger end portion covering an end of the drug container facing the plunger, the plunger end portion comprising a transparent sensor window allowing an optical signal to pass through the plunger end portion of the container casing, the optical sensor being positioned on or proximate the sensor window, the transmitter configured for transmitting an optical signal through the sensor window to the back end of the plunger and the receiver configured to receive the optical signal reflected off the plunger back end and returning through the sensor window.

In an embodiment, the plunger end portion of the container casing portion comprises a raised portion positioning the sensor window at a certain distance away from the plunger end back end allowing an optical time of flight measurement of the plunger in its initial position.

In an embodiment, said certain distance away from the plunger end back end is in a range of <NUM> to <NUM>.

In an embodiment, the delivery unit comprises a casing including a container casing portion comprising a plunger end portion covering an end of the drug container facing the plunger, the plunger end portion comprising a transparent sensor prism allowing an optical signal to pass through the plunger end portion of the container casing, the optical sensor being positioned on or proximate a face of the sensor prism, the transmitter configured for transmitting an optical signal through the sensor prism to the back end of the plunger and the receiver configured to receive the optical signal reflected off the plunger back end and returning through the sensor prism.

In an embodiment, said face of the sensor prism on which the optical sensor is mounted is substantially orthogonal to the direction of travel of the plunger.

Disclosed herein, according to a third aspect, is a drug delivery device comprising a delivery unit including a drug container, a liquid flow system, a pressurized gas source, and a casing enclosing therein the drug container, the pressurized gas source and at least a part of the liquid flow system. The drug container comprises a barrel portion and a plunger slidably mounted within the barrel portion and sealing the drug within the container at one end of the barrel portion. The drug container is contained within a container receiving cavity of a container casing portion of the casing and the container receiving cavity fluidically interconnected to a fluid outlet of the pressurized gas source in a gas tight manner. The pressurized gas source is configured to supply pressurized gas in the container receiving cavity thus applying pressure on a back end of the plunger for delivery of the liquid drug. The drug delivery device further comprises a pressure sensor fluidically coupled to the container casing for measuring a pressure within the container casing, the pressure sensor connected to an electronic control system configured to measure a pressure detected by the pressure sensor over time and to determine from the pressure measurement over time a position of the plunger over time, including a stop in movement of the plunger either due to occlusion in the drug delivery flow system or an end of travel of the plunger within a container corresponding to a container empty position.

In an advantageous embodiment, the pressurized gas source comprises a pumping system configured to pump a gas into the container receiving cavity thus applying pressure on a back end of the plunger.

In an advantageous embodiment, the pumping system is configured to pump environmental air into the container receiving cavity thus applying pressure on a back end of the plunger.

Disclosed herein, according to a fourth aspect, is a drug delivery device comprising a delivery unit including a drug container in the form of a drug cartridge containing a liquid drug therein, a liquid flow system, a pumping system and a casing within which the drug container, the pumping system and at least a part of the liquid flow system are mounted. The drug container comprises a septum sealing an end of the drug container. The liquid flow system comprises an injection delivery system including an injection needle configured for injection of the drug in an actuated state of the drug delivery device, the liquid flow system further comprising a container fluidic connection system including a septum needle mounted on a movable septum needle support, a spring pressing the septum needle support towards the septum of the drug container, and a blocking organ movable from a blocking position in which the septum needle support is held in a retracted position where the septum needle is not in contact with the septum, to an actuated position in which the septum needle support is released and allowed to travel towards the drug container septum such that the septum needle pierces through the septum under the force of the spring.

In an advantageous embodiment, the blocking organ comprises a rotatable support ring and a blocking finger extending from the support ring and rotatably movable with the support ring from a position in which the blocking finger engages the septum needle support and maintains it in the retracted position, to an actuated position in which the blocking finger disengages the septum needle support to allow it to travel to an actuator position where the septum needle pierces through the septum.

In an advantageous embodiment, the septum needle support comprises flange sections and a gap between the flange sections, the blocking finger engaging the flange section during the blocked position in which the septum needle support is retracted.

In an advantageous embodiment, the septum needle support comprises guides on opposite sites engaging complementary guide portions in the casing for slidably guiding the septum needle support from the retracted position to the septum piercing position.

In an advantageous embodiment, the injection delivery system comprises an needle actuation mechanism configured to move the injection needle from a retracted position within a housing of the drug delivery device to an extended delivery position where the injection needle projects through a base wall of the housing, the needle actuation mechanism comprising a rotary actuation disc configured to engage an actuation lever coupled to the slidable septum needle support for transfer between retracted and extended delivery positions.

In an advantageous embodiment, the actuation disc is directly coupled or integrally formed with a rotor of a pump engine of the pumping system.

In an advantageous embodiment, the actuation lever is coupled to the blocking organ to move it from the locked position to the unlocked position.

In an advantageous embodiment, the actuation lever comprises a support ring mounted around a shroud portion of the casing surrounding a cavity receiving the septum end of the drug container therein.

In an advantageous embodiment, the actuation lever comprises a lever arm extending from the rotatably support ring configured to engage an indent in the actuation disc upon initial actuation of the drug delivery device.

Disclosed herein, according to a fifth aspect, is a drug delivery device comprising a housing, a delivery unit including a drug container, and a control unit mounted within the housing, the control unit comprising an on-body sensing system including an electrode connected to an electronic control system of the control unit for measuring a capacitance value configured to detect whether the drug delivery device is positioned against a patient's skin. A skin contact wall of the housing has an inner side facing an inside of the housing in which the delivery unit and control unit are mounted, and an outer mounting side facing the outside of the housing and intended to be placed against the skin of a patient. The electrode comprises a layer of metal mounted directly against the inner side of the skin contact wall.

In an advantageous embodiment, the metal layer of the electrode consists of a metal layer directly deposited on said inner surface of the skin contact wall.

In an advantageous embodiment, the direct deposit metal layer is a galvanic plating layer.

In an advantageous embodiment, the on-body sensing system further comprises a shield in the form of a conductor surrounding the electrode.

In an advantageous embodiment, the on-body sensing system is configured to measure a capacitance value between said electrode and a ground value.

In an advantageous embodiment, the on-body sensing system comprises a second electrode insulatingly separated from said electrode which constitutes a first electrode, a potential between the first electrode and second electrode being measured to determine a capacitance value.

In an advantageous embodiment, the second electrode is formed as a metal layer directly on the inner side of the mounting wall.

In an advantageous embodiment, the second electrode is formed as a metal layer in the same manner as the first electrode.

In an advantageous embodiment, the second electrode and first electrode have interleaving portions.

Disclosed herein, according to a sixth aspect, is a method of producing a drug delivery device comprising.

the method comprising the following steps.

characterized in that steps c) and e) are performed in aseptic conditions.

In an advantageous embodiment, step f) is not performed in aseptic conditions.

In an advantageous embodiment, the cartridge pack system comprises a container casing which encompasses the prefilled drug container.

In an advantageous embodiment, the container pack system comprises a pump system.

In an advantageous embodiment, the pump system comprises a coupling interface of the pump system of the delivery unit, the pump drive providing torque to the rotor of the pumping system wherein the coupling interface is sealed by a sealing membrane to maintain sterility after step b).

In an advantageous embodiment, the housing comprises a user interface.

In an advantageous embodiment, the sterilization method of the b) is any of gamma radiation, ETO sterilization, NO2 sterilization, steam sterilization, VHP sterilization, X-ray sterilization or e-beam sterilization.

In an advantageous embodiment, the assembly steps of step e) comprise a form-fit connection.

In an advantageous embodiment, the form-fit connection provides a hermetical sealing of the prefilled drug container within the container pack system.

In embodiments of the method, the delivery unit described herein without the drug container assembled therein forms said fluidic pack, the delivery unit with the drug container assembled therein forms said container pack, and the drive unit described herein forms said control unit comprising electronic parts.

In embodiments of the method, the drug delivery device may have any one or more additional features of any of the embodiments of the device described herein.

In various embodiments, the drug container may comprise a septum at one end of the drug container, the septum being perforated by a septum needle fluidically connected to the injection needle during actuation of the drug delivery device.

In various embodiments, the drug delivery device may comprise an injection needle mounted on a movable needle support configured to move the needle from a retracted position where it is fully within the housing, to an actuated position where the needle tip projects out of a skin contact wall of the housing for injection delivery of the liquid drug.

In various embodiments, the liquid flow system may comprise an injection delivery system including the injection needle mounted on a movable needle support, connected via a conduit to a container fluidic connection system including the septum needle.

In various embodiments, the drug delivery device may further comprise a drive unit comprising a pump drive having a coupling interface coupling to a drive coupling interface of the pumping system of the delivery unit, the pump drive providing torque to the rotor of the pumping system.

In various embodiments, the drug delivery device may comprise a housing within which the delivery unit and the drive unit is assembled, the housing comprising a skin contact wall for mounting against a patient's skin, the skin contact wall comprising an adhesive patch with a protective film.

In various embodiments, for certain medical applications, the drug delivery device may be configured as a single use disposable device, and may in particular be configured for a single dose administration of the liquid drug contained in the container.

Referring to the figures, a drug delivery device <NUM> according to embodiments of the invention comprise a housing <NUM>, a delivery unit <NUM>, and a control or drive unit <NUM>, the delivery unit <NUM> and the control or drive unit <NUM> being assembled within the housing <NUM>. The housing <NUM> may be made of two or more parts allowing assembly of the delivery unit, drive unit and any other components within the housing.

In the illustrated embodiments, the drug delivery device <NUM> is a single use disposable unit for subcutaneous administration of a liquid drug (medicament). The administration may occur in a single dose over a short period of time, typically less than <NUM> hour, for instance around <NUM> minutes or less. A single use disposable drug delivery device may also be used for subcutaneous injection of a liquid drug over an extended period of time from a few hours to a few days or even up to <NUM> to <NUM> weeks. Depending on the volume of the drug to be injected, the drug delivery device may also be configured to inject the liquid drug within a few minutes.

There are various applications in which it is advantageous to provide a patient in need of a drug with a drug delivery device that the patient may wear on the patient's body, or that allows a patient to apply the device directly on his/her skin prior to use, for injection of a drug outside of a hospital or medical institution, for instance at home. For certain medical applications, there may also be the need to deliver a liquid drug within a range of time subsequent to an occurrence such as a surgical intervention, or other form of treatment in a hospital or clinic, for instance once the patient is back at home. There may also be applications in which it would be advantageous to supply the patient with a drug delivery device for injection of a medicament at certain times, for instance once a week or once a month or various other intervals depending on the drug and the treatment, without requiring the patient to have the drug administered by a healthcare professional in a clinical environment, for instance to allow the patient to perform treatment at domicile.

Although the embodiments shown in the figures concern a single use disposable drug delivery device, within the scope of the invention for various aspects described herein, a drug delivery device with a disposable portion that may be assembled to a reusable portion comprising a drive unit, electronics and power supply may also be used. The delivery unit <NUM> may be mounted in a housing of the drug delivery device and the drive unit <NUM> in a separable housing portion such that the drive unit <NUM> can be reused with subsequent delivery units. An example of a drug delivery device with single use disposable and reusable parts is described for instance in <CIT>.

The drug delivery device includes a user interface <NUM> that may include one or more buttons for actuating the drug delivery device, light and/or sound status indicators, and optionally a screen or other display for presenting information to an operator of the device.

Drug delivery devices according to embodiments of the invention may advantageously be configured as a patch device for mounting on a patient's skin. An adhesive layer (not shown) may be provided on an outer surface of a skin contact wall <NUM> of the housing <NUM>, for instance on a surface of the cover 2b, covered by a protective film that may be peeled off the adhesive layer prior to placing the adhesive layer on the patient's skin at the site of injection. A needle orifice <NUM> through the skin contact wall <NUM> is covered by the protective film <NUM> prior to use, and allows a transcutaneous injection needle <NUM> to extend therethrough and pierce the patent's skin upon activation of the drug delivery device <NUM>.

The delivery unit <NUM> comprises a drug container <NUM>, for instance a drug cartridge, containing a liquid drug <NUM>, a liquid flow system <NUM> for channeling the liquid drug to a patient subcutaneously, a pumping system <NUM>, and a casing <NUM> for housing the drug container, the liquid flow system <NUM> and pumping system <NUM>.

In embodiments, the casing <NUM> may be configured to enclose the drug container in a hermetic manner such that a gas pressure within the casing portion around the drug container may be generated for effecting the pumping action of the drug as will be described in more detail herein.

The drug container <NUM> may be of a conventional type of drug cartridge comprising a container having a barrel portion 6a, a neck portion 6b having an open end closed by a septum 6c, and a plunger <NUM> closing an open end of the barrel portion 6a, the liquid drug <NUM> to be administered to the patient being contained hermetically within the barrel portion 6a between the plunger and the septum. Such drug containers <NUM> are well-known in the pharmaceutical industry and may be used for containing in a sterile manner many different types of liquid drugs. Such drugs may also be provided in different sizes (volumes), it being understood that a drug delivery device according to embodiments of the present invention may be adjusted in dimensions to cater for different types of drug containers depending on the medical application. Embodiments of the invention may also be used with non-standard drug containers.

Although certain aspects of the invention disclosed herein require drug containers comprising a sliding plunger, it may be noted that certain other aspects of the invention disclosed herein are not limited for use to drug containers with plungers and may be used with other forms of drug containers without plungers. For instance an on-body sensing system, as will be described further on, is independent of the type of drug container that is used in the drug delivery device. Also, for instance, the container fluidic connection system <NUM>, as will be described further on, requires a drug container with a pierceable sterile barrier, but does not necessarily require a drug container with a plunger. In addition, a method of producing a drug delivery device, as will be described further on, is independent of the type of drug container that is used in the drug delivery device.

The delivery unit <NUM> incorporates the pumping system <NUM> that causes liquid from the container to be pumped to the injection needle <NUM> once the drug delivery device has been activated. The pumping system comprises a drive coupling interface <NUM> that couples to a coupling interface <NUM> of a pump drive <NUM> of the drive unit <NUM>. The drive unit thus provides the mechanical power via the coupling <NUM>, <NUM> to drive the pumping system <NUM>.

The pump engine <NUM> may advantageously comprise a design and configuration similar to the pump engine described in <CIT> or <CIT> in which a rotor <NUM> is mounted within a stator <NUM> and is rotatably and axially removable within the stator in order to pump a fluid from a fluid inlet <NUM> to a fluid outlet <NUM>. As known from the above-mentioned publications, the rotor <NUM> has a pump shaft <NUM> with first and second diameters surrounded by seals that open and close a fluid channel between the inlet and outlet as the rotor rotates and axially displaces due to a cam mechanism between the stator and rotor, whereby during the opening and closing of the valves between the fluid inlet and pumping chamber, respectively between the pumping chamber and outlet, a pumping action is performed.

In summary, the pump engine <NUM> according to a preferred embodiment includes:.

Although the pump engine design in general and the pumping action principle may be understood by referring to the above-mentioned publications, in embodiments of the present invention, the pumping system is not fluidically connected to the liquid to be administered. Rather, in embodiments of the present invention the pump engine may advantageously be used to pump air that creates a pressure on the container plunger to displace the plunger and press liquid out of the container once the septum is pierced.

In advantageous embodiments of the invention, in particular for single use and single injection of the contents of the drug container, for instance over time spanning a few minutes to <NUM> minutes, the pump engine may be used to pump air that generates a pressure on the plunger <NUM> in order to advance the plunger towards the septum and push the liquid <NUM> within the container via the liquid flow system <NUM> through the injection needle <NUM> of a subcutaneous delivery system <NUM>. In these embodiments, the pumping system <NUM> thus acts as a pneumatic drive generating air pressure within at least a portion of the casing <NUM> behind the plunger <NUM> as best illustrated in <FIG>.

An important advantage of using such pump engine in embodiments of the present drug delivery device is that there is no direct connection of fluid between the inlet and outlet at any position of the rotor and no actuation of any valves are required, such that a particularly reliable pumping of gas without leakage is ensured in an easy to operate arrangement. The pump engine <NUM> is very compact and can be driven directly by a rotary electrical motor <NUM> of a pump drive <NUM> in the drive unit <NUM> without gearing. In effect, because of the differential pumping volume displacement that is defined by the axial displacement of the rotor and the difference between the first and second diameters of the pump shaft, the pumping volume displacement rotation can be easily configured for optimal operation with an electrical motor of a given type rotating with a constant speed. Moreover, the pump engine parts can be made entirely of polymer materials and the rotor may be easily coupled to the pump drive ensuring a sterile barrier between the fluidic portion of the pump engine and the coupling interface.

It may be noted that certain aspects of embodiments of the invention described herein do not necessarily rely on a pneumatic drive for their functioning. For instance the on-body sensing system <NUM> and the plunger sensing system <NUM> using optical sensors <NUM> do not necessarily need a pneumatic drive and can also be implemented in drug delivery devices in which the pump engine acts directly on the liquid drug as described for instance in <CIT> in a conventional manner, or using other pump systems per se known in the art that act directly to draw the liquid from the container. Also, the container fluidic connection system <NUM>, that will be described in more detail hereinafter, may also be implemented with different pumping systems, for instance a pneumatic drive, or a drive that presses on the plunger mechanically as per se known, or by drawing the liquid using the engine described in <CIT>.

The drive unit <NUM> is configured principally to drive the pumping system <NUM> of the delivery unit <NUM>, but may also have additional functions such as processing sensing signals, and transmitting and receiving data from an external device via a wireless communication link, for instance using Bluetooth.

The drive unit <NUM> comprises an electronic control system <NUM> that may include a circuit board <NUM> on which is mounted electronic components including at least one microprocessor <NUM> and optionally a wireless connection module. The electronic control system further comprises a power source <NUM> for instance in the form of a battery, and a pump drive <NUM> including an electrical motor <NUM>.

An axis of the motor <NUM> may be coupled to a coupling interface <NUM> configured to engage a complementary coupling interface <NUM> of the pump engine rotor <NUM> on the delivery unit <NUM>. If the pump engine <NUM> is configured with a rotatably and axially movable rotor as discussed above, in a preferred embodiment, the drive coupling interface <NUM> may be axially slidable with respect to the motor output shaft and biased by means of a spring <NUM> that presses the motor drive coupling interface <NUM> against the coupling interface <NUM> of the pump engine rotor <NUM> as best illustrated in <FIG>.

The drive unit may further comprise a plunger sensing system <NUM> for sensing the position of the container plunger. The plunger sensing system is for determining correct operation of the drug delivery device and identifying for instance occlusion in the liquid flow system, or an end of travel of the plunger when the drug container is empty at the end of the drug administration process. Embodiments of the plunger sensing system <NUM> will be described in more detail further on.

It may be noted that the plunger sensing system <NUM> for sensing the position of a plunger according to embodiments of the invention may be implemented on various drug delivery systems having drug containers comprising a plunger, for instance on syringe devices, autoinjectors, pen injection systems (like insulin pens) or any other plunger movement of a primary packaging of fluid medicaments.

The drive unit may further comprise an on-body sensing system <NUM> for detecting whether the drug delivery device is positioned against the skin of a patient. The on-body sensing system prevents operation of the drug delivery device if it is not positioned against a patient's skin, and may also detect if the drug delivery device is removed before complete delivery of the drug. Embodiments of the on-body sensing system <NUM> will be described in more detail further on.

The liquid flow system <NUM> comprises a subcutaneous delivery system <NUM> including an injection needle <NUM> for piercing through the skin of a patient and a container fluidic connection system <NUM> including a septum needle <NUM> for piercing through the septum 6c of the container <NUM> upon actuation of the drug delivery device. The subcutaneous delivery system comprises a needle support <NUM> which is slidably mounted within the housing <NUM> along a housing slide <NUM>, the needle being mounted on the needle support and movable with the needle support <NUM> from a fully retracted position within the casing <NUM> of the delivery unit <NUM> as illustrated in <FIG>, <FIG> and <FIG> to a fully extended position during drug administration as illustrated in <FIG>, <FIG> and <FIG>.

The fluidic channel within the needle and needle support is connected to a conduit <NUM> that may advantageously be in the form of a supple tube allowing the sliding movement of the needle support from the retracted to the extended positions, the tube being connected at its other end to the container fluidic connection system <NUM>.

The container fluidic connection system <NUM> comprises a septum needle support <NUM> on which the septum needle <NUM> is mounted, the septum needle support <NUM> being slidably mounted within the housing, configured from moving from a retracted position as illustrated in <FIG>, <FIG>, <FIG>, to an extended position, as illustrated in <FIG>, <FIG>, <FIG>. In the retracted position, the septum needle <NUM> is not in contact with the drug <NUM> within the drug container, and in the extended position the septum needle has pierced through the sealing member <NUM> (sterile barrier) and septum 6c of the drug container and is in contact with the liquid <NUM> within the container.

In an advantageous embodiment, the container fluidic connection system <NUM> may be actuated at the same time as the subcutaneous delivery system <NUM>. It may however be noted that within the scope of the invention, it would be possible to actuate the container fluidic connection system <NUM> prior to actuation of the subcutaneous delivery system <NUM>, for instance in a sequential manner. The step of first connecting the septum needle <NUM> with the liquid of the drug, prior to piercing of the patient's skin with the injection needle <NUM>, could allow the fluidic connection comprising the conduit <NUM> to be filled with drug prior to injection, in order to remove air from the fluidic channels prior to injection.

The container fluidic system <NUM> in an advantageous embodiment comprises a slidable needle support <NUM> having flange sections <NUM> with guides <NUM> at outer extremities that engage slidably in complementary guides in a housing portion of the casing <NUM>. The container fluidic connection system <NUM> further comprises a blocking organ <NUM> with a blocking finger <NUM>. In a locked position in which the septum needle support <NUM> is in a retracted position as illustrated in <FIG>, <FIG>, <FIG>, the blocking finger <NUM> blocks the septum needle support in the retracted position by pressing against at least one of the flange sections <NUM>. A spring <NUM> that may for instance be in the form of a conical coil spring, presses against a rear side of the septum needle support with a spring force configured to move the septum needle support towards the drug container and through the sealing member <NUM> (sterile barrier) and the septum 6c. Other forms of springs could be provided within the scope of the invention. The blocking finger <NUM> may be moved out of engagement with the septum needle support, for instance by being moved in a gap between the flange sections <NUM>, such that the spring <NUM> pushes the septum needle support towards the sealing member <NUM> and septum 6c such that the septum needle <NUM> pierces through the sealing member and the septum.

The blocking organ <NUM> may, in an advantageous embodiment, comprise a rotatable support ring <NUM> from which the blocking finger <NUM> protrudes. The rotatable support ring <NUM> is for instance mounted around a shroud forming a cavity in which the container cap with septum 6c is inserted.

The blocking organ may be actuated to release the septum needle support allowing it to travel from the retracted to the extended position by rotation of the blocking organ <NUM>.

In an advantageous embodiment, the movement of the blocking finger <NUM> and release thereof from the septum needle support <NUM> may be performed by actuation of the pump engine <NUM> of the pumping system <NUM>. The subcutaneous delivery system <NUM> may also be actuated simultaneously by the initial rotation of the rotor <NUM> of the pump engine <NUM>.

In the present invention, the subcutaneous delivery system may comprise a configuration similar to the delivery system described in <CIT> In such configuration, the rotor <NUM> of the pump engine <NUM> comprises an actuation disc <NUM> coupled to the pump shaft <NUM>, the actuation disc comprising an indent <NUM> that engages the tip of a lever arm <NUM> connected to a support ring <NUM> of an actuation lever <NUM>. As best seen in reference to <FIG> and <FIG> and <FIG>, the support ring <NUM> of the actuation lever <NUM> is rotatably mounted around the shroud forming the cavity receiving the container cap, whereas the lever arm <NUM> extends up to a tip that is configured to catch in the indent <NUM> of the actuation disc <NUM> when the rotor <NUM> is rotated by the pump drive <NUM> of the drive unit <NUM>.

As can be seen in <FIG> and <FIG>, an initial position before first use of the drug delivery device is shown where the tip of the lever arm <NUM> rests against the outer peripheral surface of the actuation disc <NUM>. When the pumping operation is started upon actuation of the drug delivery device, the actuation disc <NUM> turns (in the illustration in an anti-clock wise direction) such that the tip of the lever arm <NUM> engages in an indent <NUM> as best seen in <FIG>. Subsequently the continued rotation of the rotor causes the actuation lever <NUM> to pivot (in the illustration in a clockwise manner as shown in <FIG> and <FIG>) until a fully actuated position shown in <FIG> where the injection needle <NUM> is fully extended. The actuation lever <NUM> is also coupled with a pin, protrusion or other organ (not visible in the illustrations) to the support ring <NUM> of the blocking organ <NUM> and causes it to rotate (in a clockwise manner illustrated in <FIG>) such that the blocking finger <NUM> thereof disengages the septum needle support <NUM>.

Thus, in the above described advantageous embodiment, the actuation of the pump drive automatically and simultaneously actuates both the subcutaneous delivery system <NUM> and container fully connection system <NUM> for administration of a drug. This simultaneous actuation upon start of the pumping system has the advantage of ensuring hermetic containment of the drug within the container until administration of the drug to the patient, thus improving sterility and shelf life duration.

As best seen in <FIG> and <FIG>, a sealing member <NUM> may be provided to cover a central orifice in front of the retracted septum needle, prior to the septum needle <NUM> piercing through the container septum.

An orifice <NUM> in the casing <NUM> through which the injection needle <NUM> extends (see <FIG>) may also comprise a sealing member that is pierced during actuation of the injection needle.

At the end of the injection cycle, the rotor <NUM> of the pump engine <NUM> may be reversed in order to pivot the actuation lever <NUM> and lever arm <NUM> in the opposite direction to move the needle support <NUM> back upwards, thus retracting the injection needle <NUM> within the casing <NUM>. The patient may then safely remove the drug delivery device without danger of anyone being pricked by the injection needle <NUM>.

In variants (not shown), an actuation of the container fluidic connection system may be performed by a different mechanism, for instance a manually actuated button on the housing, pressing the blocking finger <NUM> out of engagement with the septum needle support <NUM>. In such configuration, a sensor may be provided to prevent actuation of the subcutaneous delivery system <NUM> and the pumping system <NUM> until the container fluidic connection system <NUM> has been actuated.

In embodiments comprising a pneumatic drive, the casing <NUM> comprises a container casing <NUM> having therein a container receiving cavity <NUM> that surrounds the drug container <NUM> and is connected to a portion of a pump and needle system casing <NUM> surrounding the septum needle outlet orifice, in a hermetic manner. The interior of the container casing <NUM> is fluidically connected via a fluidic channel <NUM> to an outlet <NUM> of the pump engine <NUM> as best illustrated in <FIG>. The pneumatic flow system <NUM> is sealed from the volume within the pump and needle system casing <NUM> situated around the pump engine <NUM>, within which an inlet <NUM> on the stator <NUM> of the pump engine <NUM> is positioned to draw air into the pump engine. The casing <NUM> may thus be provided with a valve inlet or a filter inlet (not shown) to allow air to be drawn into the volume surrounding the pump engine.

Advantageously, in the pneumatic drive configuration of embodiments of the invention, the pumping system <NUM> is actuated to generate a gas pressure within the container casing <NUM> that thus applies pressure on the back end <NUM> of the plunger <NUM>. This configuration allows for a very compact delivery unit and therefore also of the drug delivery device <NUM>, since very little space is required behind the plunger because there is no mechanical drive to directly push the plunger. Also, the use of a pump engine <NUM> as described above, per se known for pumping liquids, is particularly advantageous in the application of the pneumatic drive in view of the very compact size as well as the ability to pump gas without requiring additional valves. Moreover, the pump may be driven by an electrical motor without requiring gearing. Sterilization of the delivery unit <NUM> is also easy to perform as a substantially closed unit with gamma radiation, prior to assembly with the drug container <NUM>.

Referring to <FIG>, a drug delivery device with pneumatic flow system and pneumatic drive may comprise a pressure sensor <NUM> to measure the pressure in the pneumatic flow system <NUM>. The pressure in the pneumatic flow system measured over time as illustrated in <FIG> is indicative of the displacement of the plunger <NUM>. Blockage of the plunger due to occlusion in the liquid flow system may be detected by an augmentation in the rate of increase of the pressure over time. Also, the end of travel of the plunger, in other words the emptying of the drug container may also be easily detected for instance by a rise in the rate of increase in pressure identified in section E of <FIG>.

As illustrated in <FIG>, if a pneumatic pump system as described above is used, the air pumping action is preferably delivered in a pulsed manner, whereby there is a pumping phase followed by an inactive phase where the pump is stopped such that there is a variation in the air pressure that gives a saw tooth characteristic as illustrated in <FIG> and <FIG>. Each active pumping phase may be obtained by a single rotation cycle (<NUM>° rotation) of the pump engine rotor <NUM>, or by a pre-defined plurality of rotation cycles. The inactive phase where the pump is stopped may be of a predefined duration, depending on the desired rate of drug delivery.

Evaluation of the pressure signal in the control unit <NUM> allows to obtain various information about the drug delivery device status, including:.

Examples of variants of the algorithms <NUM> to <NUM> are described below. The system information obtained from this can be processed by the control unit <NUM> of the pump system <NUM> alone or by correlating it with the feedback from other built-in sensors.

Referring to <FIG>, <FIG> and <FIG>, the amplitude p+ , p- of the pressure fluctuations decreases towards the end of delivery. As the plunger <NUM> progresses, the volume behind the plunger in the air section increases, whereby, the same volume of air is added per active pump phase. The ever-decreasing ratio of the added pump volume to the air section volume results, among other things, in a reduced increase in pressure during the active pumping phase p+. The position XStopfen of the plunger <NUM>, and thus also the volume of medication already dispensed VMedikament, correlates reciprocally with this increase in pressure, according to Boyle-Mariotte's law: <MAT>.

The constant C<NUM> depends on the air volume supplied per active pump phase and the initial volume (dead volume) of the air section C<NUM> can be easily determined experimentally.

Due to the pulsating operation of the pump, the pressure increase during the active pumping p+ phase can be compared with the pressure decrease during the inactive pumping phase p- (i.e. the pause between active pump cycles p+). This enables a statement to be made about the speed of the plug and the delivery rate.

If p-/p+ is within a cycle of pump operation and p-=<NUM>, the volume of air delivered when the pressure increases corresponds to the volume of medication delivered when the pressure drops. In this state of equilibrium, the delivery rate of the drug corresponds to that of the compressed air from the pump. Deviations from the state of equilibrium are expressed in a deviation of the ratio p-/p+ from <NUM>.

The constant C<NUM> represents the steady state plunger velocity and combines effects of friction, back pressure and pressure relative to the environment. It can be easily determined experimentally. The constant C<NUM> is calculated from the constant C<NUM> and the surface area of the plunger: <MAT>.

If the plunger <NUM> does not move or moves more slowly, the pressure in the air section behind the plunger increases. This behavior can be detected by a significant change in the ratio p-/p+ or the increase in the pressure level averaged over a longer period of time above an upper bound pressure threshold value OThreshold.

The stopping/slowing down of the plunger can have various causes:.

If the pump cannot build up any or only a low pressure in the air filled section, this is most likely due to a leak. This can be detected by comparing the pressure level averaged over a certain period of time, for instance from <NUM> to <NUM> seconds, with a lower bound pressure threshold value LThreshold.

A large amount of information can be obtained by using a single sensor which allows the system to be better monitored and made more secure. Excessive pressure, which could cause the cartridge to burst or be damaged, may be detected at an early stage.

Pressure sensors are very economical and easy to integrate. An advantage of this pneumatic plunger position sensing system is thus the very low cost and easy integration, and it is well-adapted in particular for a single injection cycle where control of the average flow rate, for instance as illustrated in <FIG>, is required and the end position of the plunger in the container should be determined. In such circumstances the accurate verification of the position of the plunger is not required. In such circumstances a very precise verification of the position of the plunger is not required, and for instance a positional measurement accuracy of plus or minus <NUM>% to <NUM>% is sufficient to detect end of delivery, occlusion, blockage, leakage, and the average rate of delivery required for the treatment. Although the accuracy of the pneumatic plunger position sensing system is lower than that of other sensing systems such as optical systems, certain treatment applications may advantageously benefit from the implementation of the pneumatic plunger position sensing system according to embodiments of this invention.

The plunger position may also be determined by other sensing means, and in another embodiment, the plunger sensing system <NUM> comprises an optical sensor <NUM> mounted on a rear end of the container facing an end <NUM> of the plunger <NUM>. The container casing portion <NUM> of the casing <NUM> comprises a sensor window <NUM> or a sensor prism <NUM>' mounted at an end portion <NUM> of the container casing <NUM> facing the plunger <NUM>.

The optical sensor <NUM> may be positioned on an outside surface of the sensor window <NUM> or sensor prism <NUM>' which is made of a transparent material for the optical signals of the optical sensor <NUM>. The optical sensor system may advantageously comprise a transmitter 71a and a receiver 71b measuring a distance of the sensor window to the back end <NUM> of the plunger via a time of flight (TOF) measurement. Advantageously, such time-of-flight optical sensors are particularly economical and easy to implement. In order to obtain a practical measurement value, the window <NUM> may be positioned on a raised plunger end portion <NUM> to have a certain minimum distance from <NUM> up to <NUM>, for instance from between <NUM> and <NUM> millimeters, in the initial position of the plunger <NUM> when the container is full so that the plunger initial position can be more easily detected by an optical time of flight measurement.

The optical sensors <NUM> may be mounted on a circuit substrate <NUM> that projects laterally out of the drive unit <NUM> as schematically illustrated in <FIG>. In a variant illustrated in <FIG>, the optical sensor may be positioned so that the light is directed orthogonally to the direction of travel of the plunger, the light being reflected via a prism <NUM>' with an internal reflecting surface for total internal reflection as per se known in the field of optics. The prism also has the effect of increasing the initial travel of the transmitted and reflected light so that a meaningful measurement of the initial position of the plunger when the container is full may be performed.

As the plunger moves towards the container empty position the accuracy of the time-of-flight measurement increases and thus a greater precision may be obtained as the containers reaching the empty position.

The optical sensor may be used with a pneumatic drive as previously described, however may also be used in drug delivery systems with other pumping technology for instance using a pump engine that directly draws fluid from the drug container and causes a displacement of the plunger <NUM> by suction (reduced pressure) within the container.

The plunger sensing system <NUM> with an optical sensor <NUM> based on a transparent window at a back end of a container casing <NUM> is thus particularly cost effective and easy to deploy in a very compact arrangement.

Referring to <FIG>, another embodiment of a drug delivery device <NUM> is shown with a different arrangement of the housing <NUM>. In this embodiment, instead of providing a container casing <NUM> extending the full length of the container <NUM>, a cap <NUM> is provided forming a plunger end portion <NUM> of the container casing, that is configured to close a container receiving cavity <NUM> within the housing <NUM>. A sealing ring <NUM> may be provided between the cap end cavity wall to hermetically close the container <NUM> within the housing <NUM>. An optical sensor <NUM> of the plunger sensing system <NUM> may be incorporated within the cap <NUM>, also positioned on a transparent sensor window <NUM>. The optical sensors <NUM> may be mounted on the circuit substrate <NUM> that is electrically interconnected to contacts <NUM> projecting an outer surface of the cap for electrical connection with complementary contacts <NUM> on the housing <NUM>. In this embodiment, the container <NUM> may thus be mounted within the housing after assembly of the drive unit <NUM> and delivery unit <NUM>, for instance for allowing insertion of the container <NUM> by a patient or a healthcare practitioner, as opposed to a factory installation.

Referring to <FIG> yet another embodiment of a drug delivery device is disclosed which also allows, similar to the embodiment of <FIG>, insertion of a drug container <NUM> by a healthcare practitioner or user after assembly of the housing, drive unit and delivery unit in the factory. In this embodiment, the rear open end of the container casing <NUM> is closed by a lid 2c hingeably coupled via a hinge coupling <NUM> to the base 2a of the housing <NUM>, and comprising a container sealing ring <NUM> that inserts and hermetically seals the rear open end of the container casing portion <NUM> once the container is inserted therein. It may be noted that in the figures of 17a and 17b portions of the drive unit are not shown to increase clarity of the illustration of the other parts.

Referring now to <FIG>, the drug delivery device according to embodiments of the invention advantageously includes an on-body sensing system <NUM> electrically connected to an electronic control system <NUM> of the drive unit <NUM>. The on-body sensing system <NUM> is based on a capacitive measurement that detects the presence of a body tissue in proximity to the capacitive sensor. Capacitive sensors for measurement the proximity of a medical device on the skin of a sensor are per se known, however conventional sensors are either not particularly reliable or are costly to integrate in a drug delivery device. In the present invention, the on-body sensing system <NUM> comprises an electrode <NUM> comprising a metal layer that is directly formed on an inside surface of the contact wall <NUM> of the housing, an outer surface of the skin contact wall <NUM> of the housing configured to be placed against the patient's skin.

The electrode <NUM> may advantageously be formed by deposition of a metal layer on the inside surface of the housing cover <NUM>, for instance a plating process. The plating process may be a galvanic plating processing, but other metal deposition techniques for directly forming a metalized layer on the inside surface of the skin contact wall <NUM> may be utilized within the scope of the present invention. The housing may be made of a thermoplastic or thermosetting polymer and is thus an insulating material. The electrode <NUM> may be connected to the electronic control system <NUM> of the drive unit <NUM> via interconnection terminals <NUM>.

The interconnection terminals <NUM> may be connected to the circuit board <NUM> of the electronic control system <NUM> at a circuit board connection end <NUM>, for instance by soldering to circuit traces on the circuit board, and extend to electrode connection ends <NUM> contacting the metal electrode layer <NUM>. The electrode connection ends <NUM> may be elastically supported, for instance by being provided at the end of a spring beam configured to press against the metal layer of the electrode <NUM> when the drive unit <NUM> is assembled within the housing <NUM>.

Electronic components such as a microprocessor <NUM> of the electronic control system <NUM> may be connected to the electrodes to measure the capacitance value, and variations in the capacitance value, for detecting when the drug delivery device is placed against a patient's skin.

Activation of the drug delivery device may be configured in the electronic control system <NUM> to be possible only when the on-body sensing system detects correct position of the drug delivery device on a patient's skin.

In a first embodiment, the on-body sensing system comprises a sensor electrode implemented as a single electrode where the capacitance between the electrode and reference potential is measured.

In a second embodiment, the sensor electrodes may also be implemented as pair of electrodes 56a, 56b where the capacitance between them is measured. This has the advantage of reducing false detection due to external factors influencing the capacitance measurement such as moisture (sweat) at the contact interface, which can be rejected by the measurement system.

An advantage of the metal layer on an inner surface of the housing <NUM> is also the large surface area that the electrode may cover for reliable reading of a changing capacitance value in view of the large capacitive coupling with the patient's skin.

In a variant, the on-body sensing system may further comprise a conductive shield frame <NUM> that surrounds the electrode, providing some shielding against disturbances from external fields. The shielding may also be connected to the circuit board <NUM> of the electronic control system with similar contacts to those described above for connecting to the electrode layer. Instead of a metal layer directly deposited on the inner surface of the housing wall that mounts against the patient's skin, the electrode may also comprise a stamped sheet metal or thin foil of conductive material that is bonded or fixed directly against an inner surface of the housing in lieu of the deposited metal layer. The conductive foil may be bonded, for instance by adhesive or welding, against the inner surface of the housing wall <NUM> in order to form a stable electrode.

Referring to <FIG>, an advantageous method of assembly of a drug delivery device according to embodiments of the invention is described. Referring first to <FIG>, production of components of a drug delivery device that must be sterilized in a highly reliable manner is disclosed. As indicated in the illustration, the single parts for a fluidic pack are manufactured and assembled, the fluidic pack corresponding to the liquid flow and pumping system <NUM>, <NUM> in the casing <NUM> of the above-described embodiments. The container cap illustrated in <FIG> corresponds to the container casing <NUM> and is assembled to the other casing parts once the drug container <NUM> has been inserted therein. The drug container components are manufactured separately and the drug container is assembled in the container cap to the fluidic pack under aseptic conditions (according to ISO standard <NUM> in the current example). Both container cap and fluidic pack, in other words the liquid flow system <NUM>, pumping system <NUM> and casing <NUM>, may be sterilized with gamma sterilization, which is very reliable for killing all pathogens. Other sterilization methods may be employed within the scope of the invention, including chemical and heat sterilization methods, including NO2 (nitrogen dioxide), VHP (vaporized hydrogen peroxide), ETO (ethylene oxide) and steam sterilization methods. The container pack formed from the assembly of these components thus corresponds to the delivery unit <NUM> which contains all the components requiring a very high degree of sterilization.

As been noted in relation to the previously described embodiments, all outlets of the delivery unit <NUM> are provided with seals, in particular a sealing membrane <NUM> covering the container fluidic connection system <NUM>, the seal ring <NUM> between the container casing <NUM> and pump and needle casing <NUM>, and the seal <NUM> covering the interface between the pumping system rotor and the drive coupling interface <NUM>. Sealing membrane <NUM> may completely cover the drive coupling interface <NUM> as illustrated in <FIG> or may cover only the gap between the rotor and the stator. The sealing membrane <NUM> may be bonded or welded across the interface forming hermetic seal, and may for instance be frangible such that the seal ruptures or breaks when the drive unit is assembled to the delivery unit and is actuated upon use of the device. Thus the delivery unit is maintained sterile and with a long shelf life until use of the drug delivery device.

The production of the fluidic pack, container cap and drug container may occur in a single manufacturing facility and assembled in the same manufacturing facility as illustrated in <FIG>.

In a variant, as depicted in <FIG>, the fluidic cap and container cap may be manufactured in a first manufacturing facility and sterilized, preferably using gamma sterilization as in the method according to <FIG>, and subsequently supplied to a second facility in which the drug container is manufactured and filled, for instance in a pharmaceutical manufacturing company. As mentioned above, other sterilization methods may be employed within the scope of the invention, including chemical and heat sterilization methods (e.g. NO2, VHP, ETO, and steam sterilization methods). The assembly of the drug container and fluidic pack and container cap to form the delivery unit <NUM> may thus be formed within the second manufacturing site that produces the container pack.

As illustrated in <FIG> and <FIG>, the sterile container pack, representing the delivery unit <NUM> in embodiments herein, may then be assembled to the electronics, representing the drive unit <NUM> in embodiments herein, and optionally other non-sterile parts for a final assembly of the drug delivery device under controlled conditions such as ISO <NUM> standards.

As illustrated in <FIG>, various configurations of the manufacturing and assembly at different sites may be performed. For instance the drug container components may be supplied to the drug manufacturer which performs the filling process, and the fluidic pack and container cap supplied to the pharmaceutical company in a second site for assembly of the container to the fluidic pack and container cap to form the cartridge pack (i. e corresponding to the delivery unit <NUM> for the embodiments described herein). The cartridge pack may then be assembled also within the site of the pharma company to the electronic parts (i. e corresponding to the drive unit <NUM> for the embodiments described herein) and other parts to the cartridge pack to form the drug delivery device.

Claim 1:
A drug delivery device (<NUM>), comprising a delivery unit (<NUM>) including a drug container (<NUM>), a liquid flow system (<NUM>), a pumping system (<NUM>), and a casing (<NUM>) enclosing therein the drug container, the pumping system and at least a part of the liquid flow system, the drug container comprising a barrel portion (6a) and a plunger (<NUM>) slidably mounted within the barrel portion and sealing the drug (<NUM>) within the container at one end of the barrel portion, the liquid flow system (<NUM>) connected fluidically to the drug container during delivery of the liquid drug , characterized in that the drug container is contained in a hermetic manner within a container receiving cavity (<NUM>) of a container casing portion (<NUM>) of the casing (<NUM>) and the container receiving cavity is fluidically interconnected to a fluid outlet (<NUM>) of the pumping system (<NUM>) in a gas tight manner, the pumping system comprising a fluid inlet (<NUM>) connected to environmental air, the pumping system configured to pump environmental air drawn in through the fluid inlet (<NUM>) into the container receiving cavity (<NUM>) generating a gas pressure within the container casing portion thus applying pressure on a back end (<NUM>) of the plunger for delivery of the liquid drug.