Drug delivery device

Abstract

A drug delivery device (1), comprising a delivery unit (3) including a drug cartridge (6) comprising a container (6a) and a plunger (12) slidably mounted within the container and sealing the drug within the container at one end of the container, and a drive unit (4) comprising an electronic control system (7), a pneumatic flow system (14) and a pneumatic pumping system (5) configured to pump air via the pneumatic flow system to a chamber back end portion behind the plunger to generate a gas pressure to advance the plunger in the container during drug delivery, the drive unit further comprising a pressure sensing system (10) including a pressure control module (20) installed in the control system and a pressure sensor (13) connected to the control system and configured to measure a gas pressure in the pneumatic flow system. The pressure sensing system is configured to detect and differentiate between an occlusion event and a full drug delivery by: - detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, - reversing the pneumatic pumping system to extract a predefined volume of gas from the pneumatic gas flow path and reduce the pressure in the gas flow path, - measuring the reduction in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system, - comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

Description

[0001] DRUG DELIVERY DEVICE

[0002] TECHNICAL FIELD

[0003] This invention relates to a drug delivery device with a pneumatic pumping system for subcutaneous administration of a liquid drug. The invention in particular relates to a drug delivery device in the form of a patch device.

[0004] DESCRIPTION OF RELATED ART

[0005] 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. 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. 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.

[0006] 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.

[0007] In order to satisfy safety and reliability requirements, many conventional patch pump drug delivery devices have complex pump mechanisms and are rather bulky. The reliability, safety, compactness and ease of use of drug delivery devices worn by a patient is important, however for single shot administration, there is a reduced need for complex motor systems since one does not need to ensure accurate intermittent bolus or basal administration over a prolonged period extending over days or weeks. For disposable components, the amount of parts and consequently cost of the disposable device is also an important consideration. Conventional patch pumps to be worn by a patient are typically too complex and costly for single shot administration applications.

[0008] It is known to provide patch pump drug delivery devices with pneumatic pumping systems, such as described in WO2022 / 194611 and EP4338770, that overcome some of the aforementioned drawbacks. Pneumatic pumping systems for use with standard plunger based drug cartridges allow to provide less complex and more economical drug delivery systems especially for single bolus administration of liquid drugs, however there is still a need to further improve safety and reliability of the drug administration and ensure complete and correct delivery while having an economical and easy to use device. Amoung the important safety features to address are to ensure correct coupling of two-part drug delivery devices having a single use disposable unit and multi-use reusable unit, use of a correctly filled drug cartridge, complete administration of the intended dose, and identification of leakage or occlusion during delivery.

[0009] SUMMARY OF THE INVENTION

[0010] In view of the foregoing, it is an object of the invention to provide a drug delivery device with a pneumatic pumping system for single shot bolus administration of a liquid drug that is safe, reliable, compact and economical to produce.

[0011] For certain applications, the drug delivery device should be provided in particular in the form of a patch device.

[0012] It is advantageous to provide a drug delivery device of the aforementioned sorts, with a multiuse reusable drive unit comprising electronics and a power source for assembly and disassembly to single use disposable delivery units comprising the drug to be administered,

[0013] It is advantageous to provide a drug delivery device that may be used for administration of liquid drugs provided in a drug cartridge with a plunger.

[0014] It is advantageous to provide a drug delivery device that is easy to use.

[0015] It is advantageous to provide a drug delivery device that has a long shelf life

[0016] Objects of the invention have been achieved by providing the drug delivery device according to claim 1. Dependent claims set forth various advantageous embodiments of the invention.

[0017] Disclosed herein is a drug delivery device, comprising a delivery unit including a drug cartridge comprising a container and a plunger slidably mounted within the container and sealing the drug within the container at one end of the container, and a drive unit comprising an electronic control system, a pneumatic flow system and a pneumatic pumping system configured to pump air via the pneumatic flow system to a chamber back end portion behind the plunger to generate a gas pressure to advance the plunger in the container during drug delivery, the drive unit further comprising a pressure sensing system including a pressure control module installed in the control system and a pressure sensor connected to the control system and configured to measure a gas pressure in the pneumatic flow system. According to a first aspect of the invention, the pressure sensing system is configured to detect and differentiate between an occlusion event and a full drug delivery by:

[0018] - detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery,

[0019] - reversing the pneumatic pumping system to extract a predefined volume of gas from the pneumatic gas flow path and reduce the pressure in the gas flow path,

[0020] - measuring the reduction in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,

[0021] - comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

[0022] In a variant, the pressure sensing system is configured to detect and differentiate between an occlusion event and a full drug delivery by:

[0023] - detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, stopping the pumping system when the threshold is detected,

[0024] - moving forward the pneumatic pumping system a predetermined number of strokes to inject a predefined volume of gas from the pneumatic gas flow path and increase the pressure in the gas flow path,

[0025] - measuring the increase in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,

[0026] - comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred. In an advantageous embodiment, the pneumatic pumping system comprises a volumetric pump with a fixed pump volume per pump stroke or cycle.

[0027] In an advantageous embodiment, the pneumatic pumping system comprises a pump engine including a stator, a rotor rotatably and axially slidably mounted at least partially in the stator, the rotor comprising a first axial extension having a first diameter and the second axial extension having a second diameter greater than the first diameter, a first valve formed by a first valve seal mounted on the stator around the first axial extension, in conjunction with a first channel in the rotor that is configured to allow fluidic communication across the first valve seal when the first valve is in an open position, and a second valve formed by a second valve seal mounted on the stator around the second axial extension, in conjunction with a second channel in a rotor that is configured to allow fluidic communication across the second valve seal when the second valve is an open position, whereby one revolution of the rotor constitutes one pump stroke or cycle.

[0028] In an advantageous embodiment, said reversing the pneumatic pumping system comprises reversing the volumetric pump one or a plurality of strokes or cycles.

[0029] In an advantageous embodiment, said reversing the pneumatic pumping system comprises reversing the volumetric pump a plurality of strokes or cycles, for instance in a range of 3 to 30 strokes or cycles preferably in a range of 5 to 25 strokes or cycles.

[0030] In an advantageous embodiment, the drug cartridge comprises a container having a cylindrical wall with an open back end in which the plunger is inserted, further comprising a sealing plug inserted in the open back end, the sealing plug comprising an orifice configured for pluggable sealing connection to a gas channel connector of the pneumatic flow system.

[0031] In an advantageous embodiment, the gas channel connector comprises a tubular end portion pluggably inserted in the orifice of the sealing plug and sealingly engaging a surface of said orifice, said tubular end portion causing said initial pressure in the pneumatic flow system after coupling of the drive unit to the delivery unit to be greater than said ambient pressure.

[0032] In an advantageous embodiment, the pneumatic flow system comprises a channel housing component within which the gas channel is formed extending between the gas channel connector and an outlet of the pneumatic pumping system. In an advantageous embodiment, the pressure sensing system is configured to determine if the delivery unit has been connected to the drive unit by detecting with the pressure sensor an initial pressure in the pneumatic flow system after coupling of the drive unit to the delivery unit and prior to activation of drug delivery and to compare, in the pressure control module, said initial pressure with an ambient pressure.

[0033] In an advantageous embodiment, the pressure sensing system is configured to detect an ambient pressure by measuring the pressure in the pneumatic flow system with the pressure sensor prior to coupling of the drive unit to the delivery unit.

[0034] In an advantageous embodiment, the pressure sensing system is configured to detect if the cartridge is filled fully with a liquid drug by computing with the pressure control module a difference between said initial pressure and said ambient pressure and comparing said difference with a pressure difference threshold stored in the control system indicative of a full cartridge.

[0035] In an advantageous embodiment, the detection of incorrect coupling of the delivery unit to the drive unit, and / or detection of a not full cartridge is configured in the control system to prevent operation of drug delivery.

[0036] In an advantageous embodiment, a plurality of pressure over time data profiles are stored in a memory of the control system for comparison with a pressure over time profile measured by the pressure sensing system, configured to detect an abnormal condition including at least an occlusion event and a gas leakage event, and optionally an excess plunger to container friction event.

[0037] Also disclosed herein is a method of controlling a drug delivery device according to any preceding embodiment comprising the steps of :

[0038] - detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, - reversing the pneumatic pumping system to extract a predefined volume of gas from the pneumatic gas flow path and reduce the pressure in the gas flow path,

[0039] - measuring the reduction in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,

[0040] - comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

[0041] In a variant, a method of controlling a drug delivery device according to any preceding embodiment comprising the steps of :

[0042] - detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, stopping the pumping system when the threshold is detected,

[0043] - moving forward the pneumatic pumping system a predetermined number of strokes to inject a predefined volume of gas from the pneumatic gas flow path and increase the pressure in the gas flow path,

[0044] - measuring the increase in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,

[0045] - comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

[0046] In an advantageous embodiment, the pneumatic pumping system comprises a volumetric pump with a fixed pump volume per pump stroke or cycle.

[0047] Said reversing the pneumatic pumping system comprises reversing the volumetric pump one or a plurality of strokes or cycles, for instance reversing the volumetric pump a plurality of strokes or cycles in a range of 3 to 30 strokes or cycles, preferably in a range of 5 to 25 strokes or cycles.

[0048] In the variant, said moving forward the pneumatic pumping system comprises moving forward the volumetric pump one or a plurality of strokes or cycles, for instance moving forward the volumetric pump a plurality of strokes or cycles in a range of 3 to 30 strokes or cycles, preferably in a range of 5 to 25 strokes or cycles.

[0049] Further objects and advantageous features of the invention will be apparent from the claims, from the detailed description, and annexed drawings, in which:

[0050] BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 is a perspective view of a drug delivery device according to an embodiment of the invention, showing a disposable delivery unit, a drug cartridge, and a reusable unit in a disassembled state;

[0052] Figure 2a is a perspective view of a portion of the drug delivery device according to an embodiment of the invention, showing a drug cartridge housing part, sealing adaptor, and pneumatic flow system;

[0053] Figure 2b is a cross-sectional view through a plane 2b-2b of figure 2a;

[0054] Figure 3 is a cross-sectional view of a portion of the drug delivery device showing a drug cartridge housing part, drug cartridge, sealing adaptor, and pneumatic flow system according to an embodiment of the invention;

[0055] Figures 4a to 4c are schematic illustrations of a pneumatic pump coupling to a drug cartridge of a drug delivery device according to an embodiment of the invention;

[0056] Figures 5a and 5b are schematic illustrations of a plot of pressure as a function of time of the pneumatic plunger system according to an embodiment of the invention;

[0057] Figure 6 is a schematic illustration of a plot of pressure as a function of time of the pneumatic plunger system according to an embodiment of the invention for occlusion and complete delivery detection;

[0058] Figures 7a and 7b are schematic illustrations of a pneumatic pump coupling to a drug cartridge of a drug delivery device and the principle of detection of complete delivery or occlusion according to an embodiment of the invention;

[0059] Figure 8 is a schematic illustration of a plot of pressure as a function of time of the pneumatic plunger system according to an embodiment of the invention for detecting assembly of the disposable drug delivery unit to the reusable control and drive unit;

[0060] Figures 9a and 9b are schematic illustrations of a pneumatic pump coupling to a drug cartridge of a drug delivery device and the principle of detection of assembly of the disposable drug delivery unit to the reusable control and drive unit according to an embodiment of the invention;

[0061] DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0062] Referring to the figures, a drug delivery device 1 for subcutaneous administration of a liquid drug (medicament) according to embodiments of the invention comprises a delivery unit 3 and a drive unit 4. The drug delivery device 1 is in particular configured for single-shot bolus administration of a drug, the delivery unit comprising a single dose of the liquid drug.

[0063] In the illustrated embodiments, the delivery unit 3 is separable from the drive unit 4, whereby the delivery unit constitutes a single use disposable unit and the drive unit constitutes a multiuse reusable unit configured for assembly and disassembly with single use, single dose, disposable units. The drive unit includes electronics and a power supply, that may be used multiple times. The delivery unit 3 is mounted in a first housing portion of the drug delivery device and the drive unit 4 in a separable second housing portion such that the drive unit 4 can be reused with subsequent delivery units. The drive unit 4 and delivery unit 3 couple together at a coupling interface 17 that is named herein the Rll-DU coupling interface 17.

[0064] Although the embodiments shown in the figures concern a two-part drug delivery device with disposable and reusable units, within the scope of the invention for certain applications, both the drive unit and delivery unit may form together a single use disposable unit, in which case the drive unit and delivery unit do not require a two-part structure for assembly and disassembly, even if such configuration is optional for a fully disposable single use drug delivery device embodiment.

[0065] The administration of the medicament may occur in a single dose over a short period of time, typically less than 1 hour, for instance around 30 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. 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.

[0066] The drug delivery device includes a user interface 16 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.

[0067] 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 may be provided on an outer surface of a skin contact wall of the housing covered by a protective film 11 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 (not shown) on the skin contact side is covered by the protective film 11 prior to use, and allows an injection needle mechanism 22 to actuate a transcutaneous injection needle (not visible) to extend therethrough and pierce the patent’s skin upon activation of the drug delivery device 1. The needle mechanism 22 in the delivery unit 3 may be coupled to an actuator 24 in the drive unit 4 for deployment of the needle upon activation of the drug delivery device. Various injection needle mechanisms and actuators are perse well known and do not need to be further described herein.

[0068] The delivery unit 3 comprises a drug cartridge 6 containing a liquid drug, a liquid flow system for channeling the liquid drug to a patient subcutaneously via the injection needle mechanism 22, and a sealing adaptor 9 configured to enclose a back end of the drug cartridge in a hermetic manner such that a gas pressure within the drug cartridge chamber portion 25a behind the plunger may be generated for effecting the pumping action of the drug, as will be described in more detail herein.

[0069] The drug cartridge 6 may be of a conventional type of drug cartridge comprising a container 6a having an outlet end closed by a septum 6c, and a plunger 12 closing an open end of the container 6a, the liquid drug to be administered to the patient being contained hermetically within the container 6a between the plunger and the septum. Such drug cartridges 6 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 cartridges depending on the medical application. Embodiments of the invention may also be used with non-standard drug cartridges.

[0070] According to an aspect of the invention, in particular for single use and single injection of the contents of the drug cartridge, for instance over time spanning a few minutes to 60 minutes, the drug delivery device incorporates a pneumatic pumping system in the drive unit 4 that pumps air to the drug cartridge and applies pressure on the plunger 12 so as to advance the plunger and cause liquid in the container to be pumped to the injection needle (not shown) once the drug delivery device has been activated.

[0071] According to an advantageous embodiment, the pneumatic pumping system may comprise a pneumatic flow system as described in EP4338770, which uses a pump engine 28 having a design and configuration similar to the pump engine described in WO 2007014363 in which a rotor is mounted within a stator and is rotatably and axially movable within the stator in order to pump a fluid from a fluid inlet to a fluid outlet. As known from the above-mentioned publications, the rotor has a pump shaft 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.

[0072] In summary, the pump engine 28 according to a preferred embodiment includes:

[0073] - a stator 28a,

[0074] - a rotor 28b slidably and rotatably mounted at least partially in the stator, the rotor comprising a first axial extension having a first diameter and a second axial extension having a second diameter greater than the first diameter,

[0075] - a first valve formed by a first valve seal mounted on the stator around the first axial extension, in conjunction with a first channel in the rotor that is configured to allow fluid communication across the first valve seal when the first valve is in an open position,

[0076] - a second valve formed by a second valve seal mounted on the stator around the second axial extension, in conjunction with a second channel in the rotor that is configured to allow fluid communication across the second valve seal when the second valve is an open position.

[0077] As described in EP4338770, and as may be implemented in an embodiment of the present invention, the pump engine is used to pump air that creates a pressure on the container plunger 12 to displace the plunger and press liquid out of the container 6 via a septum needle 18 piercing through the septum 6c of the container 6.

[0078] As known from EP4338770, an important advantage of using such a pump engine in embodiments of the 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 28 is very compact and can be driven directly by a rotary electrical motor in the drive unit 4 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.

[0079] Although the above mentioned pump engine 28 is a preferred embodiment, in the scope of the invention, other per se known volumetric pumps such as a piston pump or membrane pump may be implemented instead of the pump engine 28. The drive unit 4 is configured principally to drive the pumping system 5, 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.

[0080] The drive unit 4 comprises an electronic control system 7 that may include at least one microprocessor and optionally a wireless connection module. The electronic control system further comprises a power source for instance in the form of a battery 29, and an electrical motor 27 to drive the pump engine 28 of the pneumatic pumping system 5.

[0081] The drive unit further comprises a pressure sensing system 10 including a gas pressure sensor 13 in the pneumatic flow system 14 and a pressure control software module 20 for computing the displacement and position of the cartridge plunger 12 based inter alia on the pressure sensor output and on operation of the pneumatic pumping system 5. The gas pressure sensor 13 is configured to measure pressure in the pneumatic flow system and may be further configured to measure ambient pressure prior to coupling of the drive unit to the delivery unit. In a variant, the pressure sensing system may comprise a separate ambient pressure sensor 13a for measuring ambient pressure. The ambient pressure sensor may be mounted in the drive unit on or within a non-sealed housing portion with access to environmental air such that ambient pressure may be correctly sensed. The pressure sensing system 10 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 cartridge is empty at the end of the drug administration process. Embodiments of the pressure sensing system 10 will be described in more detail further on.

[0082] The delivery unit 3 may comprise a cartridge casing 30 having therein a cartridge receiving cavity 31 into which the drug cartridge 6 is inserted prior to assembly of the disposable delivery unit 3 to the reusable drive unit 4. The sealing adaptor 9 is configured to enclose a back end of the drug cartridge in a hermetic manner such that a gas pressure within the drug cartridge portion 25a behind the plunger 12 may be generated for effecting the pumping action of the drug. The sealing adaptor comprises a sealing plug 23 inserted inside an end of the container 6a. The sealing adaptor may further comprise a cap 19 that mounts over an end of the container. Such a sealing adaptor may comprise for instance the features known from EP4338770.

[0083] The pneumatic flow system 14 fluidically interconnects the pump engine 28 to the plunger 12, and comprises a gas flow channel 8 formed in a channel housing component 15 mounted in the drive unit 4, the channel housing component 15 comprising a gas channel connector 32 configured for pluggable insertion in an orifice 26 extending through the sealing plug 23. In embodiments with a disposable delivery unit and reusable drive unit that may be coupled together for use and uncoupled after use, the plugging insertion of the gas channel connector in the sealing plug allows also unplugging after use.

[0084] The channel housing component 15 may be integrally molded or formed within a housing base or cover of the drive unit 4, or may be formed as a separate component that is assembled to the drive unit. In the latter case, the channel housing component 15 may comprise a first end that engages sealingly over an outlet of the pump engine 28, and the other end branching across to the position of the drug cartridge and presenting the gas connector 32 for insertion in the plugging orifice 26 of the sealing plug 23. The gas connector 32 may comprise a tube with a slightly tapered or conical outer surface for easy insertion into the sealing plug orifice 26, whereby compressible elastic sealing ribs provided around the plugging orifice 26 sealingly engaging the outer surface of the tube of the gas connector 32.

[0085] The pneumatic pumping system 5 is actuated to generate a gas pressure in the chamber back end portion 25b to advance the plunger 12 for drug delivery. This configuration allows for a very compact delivery unit and therefore also of the drug delivery device 1 , 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 28 as described above, per se known for pumping liquids, is particularly advantageous in the application of the pneumatic pumping system 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 27 without requiring gearing. Sterilization of the delivery unit 3 is also easy to perform as a substantially closed unit with gamma radiation, prior to assembly with the drug cartridge 6.

[0086] Referring to figures 1 and 4a to 9b, the pressure sensing system 10 comprises a pressure sensor 13 to measure the pressure in the gas channel 8 and therefore in the full gas path from pump engine to plunger of the pneumatic flow system 14. The pressure sensor is connected to the electronic control system 7. The pressure variation in the pneumatic flow system measured and computed over time by the pressure control module 20, as illustrated in figures 5a and 5b is indicative of the displacement of the plunger 12. Figure 5a shows a pressure over time profile for a correctly functioning device indicated here as the “normal case”. Situations in which there is a malfunction or non-optimal functioning of the drug delivery device are illustrated in figure 5b as “abnormal cases. These may include air leakage from the start of delivery, air leakage during delivery, excessive friction of the plunger 12 in the container 6, and occlusion. Blockage of the plunger due to occlusion in the liquid flow system may be detected in the control system by a rapid augmentation in the rate of increase of the pressure measured by the pressure sensor over time, as opposed to excessive friction which causes a slower increase of measured pressure over time. Also, the end of travel of the plunger, in other words the emptying of the drug cartridge may also be easily detected for instance by a rise in the rate of increase in measured pressure identified in figure 5a as “plunger stopped”.

[0087] Although the plots of pressure over time are shown as smooth curves / lines, it may be noted that the air pumping action is preferably delivered in a pulsed manner such that the variation in the air pressure when observed in greater detail has a saw tooth characteristic instead of a smooth line.

[0088] Referring to figures 4a, 8 and 9a, prior to coupling of the delivery unit to the drive unit, the gas flow channel 8 of the pneumatic flow system 14 is at ambient pressure and the pressure sensor 13 measures this ambient pressure. In a variant, a separate ambient pressure sensor 13a may be used to measure ambient pressure. Upon coupling of the delivery unit to the drive unit, the gas flow channel 8 of the pneumatic flow system 14 is closed to the external environment and the gas contained in the full gas path from pump engine to plunger of the pneumatic flow system 14 is sealed off from the external environment. The pneumatic flow system sealing connection at the delivery unit to drive unit interface is elastic and compresses such that before full coupling, but after the initial sealing at the interface has occurred, the gas inside the gas flow channel 8 is slightly compressed and this initial compression is measured by the pressure sensor as a pressure greater than the ambient pressure measured before coupling. More specifically, in the illustrated embodiments of figures 2b to 3, the nozzle of the connector 32 goes into the orifice 26 of the sealing plug 32, which compresses a certain amount of air in the pneumatic flow system gas path. The pressure sensor 13 and pressure control module 20 can detect the pressure increase, which has certain characteristics as illustrated in figure 8:

[0089] □ Previous long plateau (ambient pressure)

[0090] □ Steep increase (like a step)

[0091] □ Second long stable plateau

[0092] The pressure increase from the uncoupled to the coupled state allows to determine:

[0093] □ If the delivery unit has been connected to the drive unit, and

[0094] □ If the cartridge is full or empty.

[0095] In effect, the volume of gas in the full gas path includes the volume of gas present in the chamber back end portion 25a, whereby the variation in pressure due to the elastic coupling interface, such as the insertion of the connector 32 nozzle in the sealing plug 23 orifice 26, depends on the position of the plunger 12 in container 6. If the cartridge is empty, such that the plunger is at the front end of the container and the chamber back end portion 25a is at its largest, the variation in pressure upon coupling of the delivery unit to the reusable unit will be smaller than if the cartridge is full, where the plunger is at the back end of the container and the chamber back end portion 25a is at its smallest. A partially full cartridge will result in a pressure variation upon coupling that is in between the values of empty and full. Thus, the pressure sensing system may include, in the pressure control module 20 of the control system, one or more stored reference pressure profiles that allow to determine from the pressure variation measured by the pressure sensor 13 whether the cartridge is full or not. This would allow for instance to prevent operation of the drug delivery device, or at least to provide a warning to a user, if the drug cartridge is not full.

[0096] The detection of the cartridge full and correct coupling of the delivery unit to the drive unit may be configured in the control system to activate and allow operation of the drug delivery.

[0097] In an embodiment, the drug delivery device may be configured for use with partially filled drug cartridges, for instance for different doses of liquid drug to be administered without change in the cartridge container size, whereby the pressure sensing system 10 may be configured to verify the state of fill of the drug cartridge upon coupling and to allow or prevent operation of the drug delivery device, depending on the dose to be administered set in the control system of the drug delivery device.

[0098] Referring to figures 6, 7a and 7b, the pressure sensing system 10 is configured to verify if complete delivery of the liquid drug has occurred, of if an occlusion has occurred and thus prevented complete delivery of the intended dose of medication. It is known that if the plunger stops either due to an occlusion or complete delivery, the pressure increases with a steep rate and this can be detected by the pressure sensing system 10. However, if occlusion occurs close to the position of full delivery, it may be difficult to reliably detect whether full delivery has occurred or whether an occlusion has occurred prior to full delivery.

[0099] In order to ensure safety and reliability of the device, according to an aspect of the invention, the control system is configured to control the pneumatic pumping system 25 to reverse operation and extract a predetermined volume of gas from the gas flow path (which includes the volume of the chamber back end portion 25a), the predetermined volume being at the pressure in the gas flow path. If the pneumatic pumping system is a volumetric type of pump, having a pump engine 28 as described previously and illustrated in figure 2c, or having other per se known volumetric pump designs such as a piston pump or membrane pump, the predetermined volume may be extracted by reversing operation of the pump a predetermined number of strokes. For instance, the pump engine 28 may be reversed by reversing the rotation direction of the rotor 28b a predetermined number of revolutions, which may be one, two, or more than two revolutions in reverse. For other types of volumetric pumps, the reverse operation may for instance be one, two of more than two piston strokes, or membrane strokes.

[0100] The reverse operation for a predetermined number of strokes of the pneumatic pumping system may be operated upon detecting with the pressure sensor 13 a pressure reaching a predefined threshold stored in the pressure control module, or detecting with the pressure sensor 13 a pressure increase slope above a predefined pressure increase slope threshold. After reaching the predefined threshold pressure or predefined pressure increase slope threshold, the control system commands the pump in reverse for a predetermined number of strokes (e.g. rotor revolutions) to reduce the pressure and create a delta of pressure drop AP.

[0101] The pressure sensor measures the pressure drop AP caused by a defined amount of pump strokes, for instance a predefined number of turns (e.g. in a range of 5 to 30 revolutions) of the rotor 28b in reverse rotation. The multiple reverse strokes (e.g. reverse rotor revolutions) increases the accuracy of the pressure variation measurement, however the concept could already work with only 1 revolution in reverse.

[0102] In a variant, it is also possible to drive the rotor 28b of the pump engine 28 a predetermined number of revolutions, which may be one, two, or more than two revolutions in a forward direction and to measure the delta of pressure rise AP for the predetermined number of revolutions.

[0103] The predetermined forward operation of the pneumatic pumping system may be operated upon detecting with the pressure sensor 13 a pressure reaching a predefined threshold stored in the pressure control module, or upon detecting with the pressure sensor 13 a pressure increase slope reaching a predefined threshold pressure increase slope stored in the pressure control module. After reaching the predefined threshold, the control system commands the pump in forward direction the predetermined number of revolutions to increase the pressure and create a delta of pressure AP. The pressure sensor measures the pressure rise AP caused by a defined amount of pump strokes, for instance a predefined number of turns (e.g. in a range of 5 to 30 revolutions) of the rotor 28b in forward rotation.

[0104] The reverse rotation a predetermined number of strokes however provides greater sensitivity and measurement accuracy and is preferred,

[0105] Using the ideal gas law (PV = nRT) the volume of gas contained in the full gas path may be computed in the control system by the pressure control module 20. Once the complete volume of the gas flow path is computed, the initial gas flow path volume before drug delivery may be subtracted to compute the variation of the volume in the cartridge chamber due to the plunger displacement, which corresponds to the volume of drug delivered.

[0106] Based on this computation by the pressure control module 20 of the pressure sensing system 10 it is determined if the plunger 12 has stopped due to an occlusion or due to a complete delivery where the plunger has hit the front end of the container. The computation of occlusion and complete delivery may be explained with reference to figure 7b: It is assumed that the temperature remains constant during the pressure drop since it is created in a short period of time, for instance typically less than 60 seconds. The ambient pressure is known, because it is measured by the pressure sensing system 10 before the coupling of the delivery unit 3 to the reusable unit 4. The nominal dead volume of the pump and stroke volume of the pump is a known characteristic and a property of the pump. Before decreasing the pressure, the system is P1 & V1. V1 is the volume to be estimated. This volume is constant (plunger has stopped). V1 is the only unknown. The pressure sensor 13 provides the measured pressure values P1 and P2. When the pump performs 1 turn in reverse, 1 pump volume of gas is removed from V1. The pressure in V1 becomes P2. After decreasing the pressure, the system is P2 & V1 . The volume to estimate has still not changed. The system of equations can be solved by various per se known methods.

[0107] It may be noted that the pressure sensing system 10 may also be used to determine an estimation of the initial gas flow path volume using the same computation method described above to compute the full gas path volume at the end of the delivery: After coupling of the delivery unit 3 to the reusable unit 4, the pressure may be increased a predefined amplitude, below the force required to move the plunger forward in the container to prevent the plunger from moving, and subsequently reducing the pressure with a reverse operation of the pneumatic pumping system in order to create a pressure variation AP. It may be noted that the predefined pressure amplitude may be less than the stick-slip friction force of the plunger, or if the cartridge septum 6c is not yet pierced at the time of the initial volume estimation computation, the plunger displacement will be blocked by the substantially incompressible liquid drug and the applied pressure may be higher than the plunger -container friction.

[0108] 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 while at the same time offering a high level of safety and reliability in ensuring correct administration of the intended dose of medication. List of features

[0109] Drug delivery device 1

[0110] Housing 2

[0111] Skin contact wall

[0112] Needle orifice

[0113] Adhesive layer

[0114] Protective film 11

[0115] Delivery unit 3 (disposable unit - DU) Drug

[0116] Drug cartridge 6

[0117] Container 6a

[0118] Container wall Chamber 25

[0119] Chamber back end portion 25b (gas volume)

[0120] Chamber front end portion 25a (liquid drug volume) Outlet end

[0121] Septum 6b Back end

[0122] Plunger 12

[0123] Sealing adaptor 9

[0124] Cap 19

[0125] Sealing plug 23

[0126] Cartridge casing 30

[0127] Cartridge receiving cavity 31

[0128] Septum needle 18

[0129] Injection needle mechanism 22

[0130] Drive unit 4 (reusable unit - RU)

[0131] Control system 7

[0132] Microprocessor

[0133] Wireless connection module Pressure control module 20 Pump drive control 21

[0134] Power source (battery) 29

[0135] Injection needle actuator 24

[0136] Pump Motor 27

[0137] Pump engine 28

[0138] User interface 16

[0139] Pressure sensing system 10

[0140] Pressure sensor 13

[0141] Pressure control module 20

[0142] RU-DU coupling interface 17 Pneumatic pumping system 5

[0143] Pump Motor 27

[0144] Pump engine 28

[0145] Stator 28a

[0146] Fluid inlet

[0147] Fluid outlet

[0148] Rotor 28b Seals

[0149] Pneumatic flow system 14

[0150] Channel housing component 15 Connector 32 Gas flow channel 8

Claims

1. CLAIMS1. A drug delivery device (1), comprising a delivery unit (3) including a drug cartridge (6) comprising a container (6a) and a plunger (12) slidably mounted within the container and sealing the drug within the container at one end of the container, and a drive unit (4) comprising an electronic control system (7), a pneumatic flow system (14) and a pneumatic pumping system (5) configured to pump air via the pneumatic flow system to a chamber back end portion behind the plunger to generate a gas pressure to advance the plunger in the container during drug delivery, the drive unit further comprising a pressure sensing system (10) including a pressure control module (20) installed in the control system and a pressure sensor (13) connected to the control system and configured to measure a gas pressure in the pneumatic flow system, characterized in that the pressure sensing system is configured to detect and differentiate between an occlusion event and a full drug delivery by:- detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery,- reversing the pneumatic pumping system to extract a predefined volume of gas from the pneumatic gas flow path and reduce the pressure in the gas flow path,- measuring the reduction in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,- comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

2. The drug delivery device of the preceding claim wherein the pneumatic pumping system comprises a volumetric pump with a fixed pump volume per pump stroke or cycle.

3. The drug delivery device of the preceding claim, wherein the pneumatic pumping system comprises a pump engine (28) including- a stator (28a),- a rotor (28b) rotatably and axially slidably mounted at least partially in the stator, the rotor comprising a first axial extension having a first diameter and the second axial extension having a second diameter greater than the first diameter,- a first valve formed by a first valve seal mounted on the stator around the first axial extension, in conjunction with a first channel in the rotor that is configured to allow fluidic communication across the first valve seal when the first valve is in an open position, and- a second valve formed by a second valve seal mounted on the stator around the second axial extension, in conjunction with a second channel in a rotor that is configured to allow fluidic communication across the second valve seal when the second valve is an open position,- whereby one revolution of the rotor constitutes one pump stroke or cycle.

4. The drug delivery device of any preceding claim 2-3 wherein said reversing the pneumatic pumping system comprises reversing the volumetric pump one or a plurality of strokes or cycles.

5. The drug delivery device of the preceding claim wherein said reversing the pneumatic pumping system comprises reversing the volumetric pump a plurality of strokes or cycles, for instance in a range of 3 to 30 strokes or cycles preferably in a range of 5 to 25 strokes or cycles.

6. The drug delivery device of any preceding claim, wherein the drug cartridge comprises a container (6) having a cylindrical wall with an open back end in which the plunger is inserted, further comprising a sealing plug (23) inserted in the open back end, the sealing plug comprising an orifice (26) configured for pluggable sealing connection to a gas channel connector (32) of the pneumatic flow system.

7. The drug delivery device of the preceding claim wherein the gas channel connector (32) comprises a tubular end portion pluggably inserted in the orifice (26) of the sealing plug and sealingly engaging a surface of said orifice, said tubular end portion causing said initial pressure in the pneumatic flow system after coupling of the drive unit to the delivery unit to be greater than said ambient pressure.

8. The drug delivery device of any preceding claim wherein the pneumatic flow system (14) comprises a channel housing component (15) within which the gas channel (8) is formed extending between the gas channel connector (32) and an outlet of the pneumatic pumping system.

9. The drug delivery device of any preceding claim wherein the pressure sensing system is configured to determine if the delivery unit has been connected to the drive unit by detecting with the pressure sensor an initial pressure in the pneumatic flow system after coupling of the drive unit to the delivery unit and prior to activation of drug delivery and to compare, in the pressure control module, said initial pressure with an ambient pressure.

10. The drug delivery device of the preceding claim wherein the pressure sensing system is configured to detect an ambient pressure by measuring the pressure in the pneumatic flow system with the pressure sensor prior to coupling of the drive unit to the delivery unit.

11. The drug delivery device of either of the two directly preceding claims wherein the pressure sensing system is configured to detect if the cartridge is filled fully with a liquid drug by computing with the pressure control module a difference between said initial pressure and said ambient pressure and comparing said difference with a pressure difference threshold stored in the control system indicative of a full cartridge.

12. The drug delivery device of any preceding claim 9-11 wherein the detection of incorrect coupling of the delivery unit to the drive unit, and / or detection of a not full cartridge is configured in the control system to prevent operation of drug delivery.

13. The drug delivery device of any preceding claim wherein a plurality of pressure over time data profiles are stored in a memory of the control system for comparison with a pressure over time profile measured by the pressure sensing system, configured to detect an abnormal condition including at least an occlusion event and a gas leakage event, and optionally an excess plunger to container friction event.

14. A method of controlling a drug delivery device according to any preceding claim comprising the steps of :- detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery,- reversing the pneumatic pumping system to extract a predefined volume of gas from the pneumatic gas flow path and reduce the pressure in the gas flow path,- measuring the reduction in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,- comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

15. The method of the preceding claim, wherein the pneumatic pumping system comprises a volumetric pump with a fixed pump volume per pump stroke or cycle and wherein said reversing the pneumatic pumping system comprises reversing the volumetric pump one or a plurality of strokes or cycles, for instance reversing the volumetric pump a plurality of strokes or cycles in a range of 3 to 30 strokes or cycles, preferably in a range of 5 to 25 strokes or cycles.

16. A drug delivery device (1), comprising a delivery unit (3) including a drug cartridge (6) comprising a container (6a) and a plunger (12) slidably mounted within the container and sealing the drug within the container at one end of the container, and a drive unit (4) comprising an electronic control system (7), a pneumatic flow system (14) and a pneumatic pumping system (5) configured to pump air via the pneumatic flow system to a chamber back end portion behind the plunger to generate a gas pressure to advance the plunger in the container during drug delivery, the drive unit further comprising a pressure sensing system (10) including a pressure control module (20) installed in the control system and a pressure sensor (13) connected to the control system and configured to measure a gas pressure in the pneumatic flow system, characterized in that the pressure sensing system is configured to detect and differentiate between an occlusion event and a full drug delivery by:- detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery,- stopping the pumping system,- moving forward the pneumatic pumping system a predetermined number of strokes to inject a predefined volume of gas from the pneumatic gas flow path and increase the pressure in the gas flow path,- measuring the increase in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,- comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

17. The drug delivery device of the preceding claim wherein the pneumatic pumping system comprises a volumetric pump with a fixed pump volume per pump stroke or cycle.

18. The drug delivery device of the preceding claim, wherein the pneumatic pumping system comprises a pump engine (28) including- a stator (28a),- a rotor (28b) rotatably and axially slidably mounted at least partially in the stator, the rotor comprising a first axial extension having a first diameter and the second axial extension having a second diameter greater than the first diameter,- a first valve formed by a first valve seal mounted on the stator around the first axial extension, in conjunction with a first channel in the rotor that is configured to allow fluidic communication across the first valve seal when the first valve is in an open position, and- a second valve formed by a second valve seal mounted on the stator around the second axial extension, in conjunction with a second channel in a rotor that is configured to allow fluidic communication across the second valve seal when the second valve is an open position,- whereby one revolution of the rotor constitutes one pump stroke or cycle.

19. The drug delivery device of any preceding claim 17-18 wherein said moving forward the pneumatic pumping system comprises moving forward the volumetric pump one or a plurality of strokes or cycles.

20. The drug delivery device of the preceding claim wherein said moving forward the pneumatic pumping system comprises moving forward the volumetric pump a plurality of strokes or cycles, for instance in a range of 3 to 30 strokes or cycles preferably in a range of 5 to 25 strokes or cycles.

21. The drug delivery device of any preceding claim 16-20, wherein the drug cartridge comprises a container (6) having a cylindrical wall with an open back end in which the plunger is inserted, further comprising a sealing plug (23) inserted in the open back end, the sealing plug comprising an orifice (26) configured for pluggable sealing connection to a gas channel connector (32) of the pneumatic flow system.

22. The drug delivery device of the preceding claim wherein the gas channel connector (32) comprises a tubular end portion pluggably inserted in the orifice (26) of the sealing plug and sealingly engaging a surface of said orifice, said tubular end portion causing said initial pressure in the pneumatic flow system after coupling of the drive unit to the delivery unit to be greater than said ambient pressure.

23. The drug delivery device of any preceding claim 16-22, wherein the pneumatic flow system (14) comprises a channel housing component (15) within which the gas channel (8) is formed extending between the gas channel connector (32) and an outlet of the pneumatic pumping system.

24. The drug delivery device of any preceding claim 16-23, wherein the pressure sensing system is configured to determine if the delivery unit has been connected to the drive unit by detecting with the pressure sensor an initial pressure in the pneumatic flow system after coupling of the drive unit to the delivery unit and prior to activation of drug delivery and to compare, in the pressure control module, said initial pressure with an ambient pressure.

25. The drug delivery device of the preceding claim wherein the pressure sensing system is configured to detect an ambient pressure by measuring the pressure in the pneumatic flow system with the pressure sensor prior to coupling of the drive unit to the delivery unit.

26. The drug delivery device of either of the two directly preceding claims wherein the pressure sensing system is configured to detect if the cartridge is filled fully with a liquid drug by computing with the pressure control module a difference between said initial pressure and said ambient pressure and comparing said difference with a pressure difference threshold stored in the control system indicative of a full cartridge.

27. The drug delivery device of any preceding claim 24-26, wherein the detection of incorrect coupling of the delivery unit to the drive unit, and / or detection of a not full cartridge is configured in the control system to prevent operation of drug delivery.

28. The drug delivery device of any preceding claim 16-27, wherein a plurality of pressure over time data profiles are stored in a memory of the control system for comparison with a pressure over time profile measured by the pressure sensing system, configured to detect an abnormal condition including at least an occlusion event and a gas leakage event, and optionally an excess plunger to container friction event.

29. A method of controlling a drug delivery device according to any preceding claim 16-28 comprising the steps of :- detecting with the pressure sensor a rate of increase of the pressure and comparing with the pressure control module the rate of increase with a threshold rate of increase stored in a memory of the control module, said threshold rate of increase indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, or detecting with the pressure sensor a pressure in the gas flow path and comparing with the pressure control module said pressure with a threshold pressure stored in a memory of the control module, said threshold pressure indicative of a stop in the plunger displacement either due to an occlusion or complete delivery, stopping the pumping system when the threshold is detected,- moving forward the pneumatic pumping system a predetermined number of strokes to inject a predefined volume of gas from the pneumatic gas flow path and increase the pressure in the gas flow path,- measuring the increase in pressure and computing the volume of gas contained in the full gas path with the pressure sensing system,- comparing the computed volume of gas with a value stored in the memory of the control unit corresponding to a volume of the gas path at a plunger position of full delivery and determining from the comparison whether full delivery or only partial delivery of the drug has occurred.

30. The method of the preceding claim, wherein the pneumatic pumping system comprises a volumetric pump with a fixed pump volume per pump stroke or cycle and wherein said moving forward the pneumatic pumping system comprises moving forward the volumetric pump one or a plurality of strokes or cycles, for instance moving forward the volumetric pump a plurality of strokes or cycles in a range of 3 to 30 strokes or cycles, preferably in a range of 5 to 25 strokes or cycles.

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