초록 ▼

Medicament devices include a sealed medicament dose container comprising a cell based medicament that is stored at a temperature less than about −40 degrees Celsius, then thawed into a liquid prior to administration and a medicament dose cartridge configured and sized to snugly hold the dose contain

Medicament devices include a sealed medicament dose container comprising a cell based medicament that is stored at a temperature less than about −40 degrees Celsius, then thawed into a liquid prior to administration and a medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament. Related dose containers, retainers and extraction/dispensing systems are also described.

대표청구항 ▼

1. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall with a perime

1. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall with a perimeter having a pair of substantially parallel spaced apart long sides that enclose an interior chamber and that merge into opposing first and second closed short ends;a medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament; anda dose retainer comprising a frame and a base portion, wherein the dose retainer is configured to sandwich the dose container between the frame and the base and define a unitary dose assembly adapted for cryogenic storage separate from the cartridge, and wherein the dose assembly is sized and configured to be snugly held in the dose cartridge prior to extraction of the liquid medicament. 2. A device according to claim 1, wherein the dose cartridge has a body with greater rigidity than that of the dose container and is configured to substantially enclose the dose container therein, wherein the substantially tubular body has at least one flat wing extending outward from a respective long side about a length of the substantially tubular body, and wherein the medicament dose container is between about 5-10 cm long. 3. A device according to claim 1, wherein the dose cartridge has a body with greater rigidity than that of the dose container, and wherein the frame is configured so that, when the frame is closed about the medicament dose container, the dose cartridge encases an entire outer perimeter of the dose container but is configured to expose an outer surface of the medicament dose container to environmental conditions. 4. A device according to claim 1, wherein the device is a unit dose single-use disposable device. 5. A device according to claim 1, wherein the liquid medicament is in a quantity sufficient to provide a plurality of sub-doses of about 0.2 ml each, wherein the sealed medicament container with the medicament is configured to be stored at a temperature that is below about −40 degrees Celsius. 6. A device according to claim 1, wherein the medicament comprises a cell-based vaccine, and wherein the sealed medicament container with the medicament is stored at a temperature that is less than about −80 degrees Celsius prior to administration. 7. A device according to claim 1, further comprising a portable package of liquid cryogen configured and sized to hold the unitary dose assembly in a frozen state during shipment, wherein the sealed medicament dose container with the medicament in the cartridge are held at between about (a) −70 degrees Celsius to about −95 degrees Celsius for a least a portion of a storage period or during shipment or during at least a portion of a storage period and during shipment or (b) −120 degrees Celsius to about −196 degrees Celsius for a least a portion of a storage period or during shipment or during at least a portion of a storage period and during shipment. 8. A device according to claim 7, wherein the liquid cryogen comprises liquid nitrogen. 9. A device according to claim 1, wherein the device includes an injection needle in communication with the dose container held by the dose cartridge that is configured to directly inject the medicament from the dose container into a patient. 10. A device according to claim 1, further comprising: a first syringe that is adapted to be in fluid communication with the dose container while the dose container is held by the dose cartridge. 11. A device according to claim 1, further comprising: a needle in fluid communication with the liquid medicament in the dose container;a one-way flow valve in fluid communication with the needle; anda liquid expulsion system held in the medicament dose cartridge, the liquid expulsion system comprising with a unidirectional roller configured to contact and roll against the dose container during use, the roller in communication with a roller guide keyed to a pair of spaced apart rails. 12. A device according to claim 1, further comprising a needle and a needle heater unit sized and configured to heat the needle at a dose delivery site to a temperature sufficient to sterilize the needle, wherein the needle is heated and advanced to pierce or puncture the dose container while heated. 13. A device according to claim 1, further comprising a cutting member and a needle in the cartridge whereby the dose container or the cutting member and the needle axially translate to cut the dose container to define an entry port that the needle enters. 14. A device according to claim 1, wherein the dose cartridge comprises a stepped fixed volume dispensing mechanism that includes a manually depressible plunger that communicates with a pressing member, the pressing member residing outside and in abutting contact with the dose container outer wall, and wherein the dispensing mechanism slidably advances the pressing member fixed different distances in the cartridge to dispense a plurality of fixed amounts of the liquid medicament from the dose container. 15. A device according to claim 1, wherein the liquid medicament is a cell-based vaccine provided in an amount sufficient to provide a plurality of sub-doses of about 0.2 ml. 16. A device according to claim 1, further comprising a shipping container having a cryogenic storage chamber, wherein the unitary dose assembly is held in the cryogenic storage chamber prior to insertion in the cartridge. 17. A device according to claim 1, wherein the dose container has sufficient rigidity to maintain its shape with and without liquid medicament held therein. 18. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall with a perimeter having a pair of substantially parallel spaced apart long sides that enclose an interior chamber and that merge into opposing first and second closed short ends; anda medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament,wherein the dose cartridge comprises a first end portion having an internal needle that does not contact a patient and is held in a non-use retracted position inside the dose cartridge during storage and is configured to translate along a fixed path inside the dose cartridge from the non-use retracted position to an extraction position whereby the internal needle pierces the dose container and is in fluid communication with the liquid medicament during extraction of the medicament. 19. A device according to claim 18, wherein the dose cartridge further comprises an external locking member in communication with the internal needle to prevent the internal needle from inadvertently piercing the dose container. 20. A device according to claim 18, wherein the dose cartridge encloses the dose container has a second end portion axially opposed from the first end portion, the second end portion being open and configured to slidably receive the dose container therein, wherein the internal needle translates inward from a location proximate the first end portion of the dose cartridge to enter the first end of the dose container. 21. A device according to claim 18, wherein the dose cartridge has a solid outer wall that encloses the dose cartridge and a second end portion axially opposed from the first end portion, the second end portion being configured to slidably receive the dose container therein, further comprising a plug member configured to sealably close the second end portion of the dose cartridge. 22. A device according to claim 18, wherein the sealed dose container is held in a sealed state enclosing the medicament that is stored frozen, then thawed into a liquid prior to administration and, in the sealed state, the sealed dose container is devoid of movable internal components that force the medicament out of the dose container, and wherein the dose cartridge first end portion is adapted to slidably receive a syringe in a manner that places the syringe in fluid communication with the internal needle to allow a dose amount of the medicament to be withdrawn by the internal needle and directed into the syringe. 23. A device according to claim 18, wherein the dose cartridge further comprises a laterally extending interior wall residing inside an outer wall of the dose cartridge between the internal needle and the dose container proximate but spaced apart from the first end portion of the dose cartridge when the internal needle is in a retracted configuration, and wherein the internal needle is configured to travel past the interior wall when the internal needle moves to an extended configuration to pierce the dose container. 24. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall with a perimeter having a pair of substantially parallel spaced apart long sides that enclose an interior chamber and that merge into opposing first and second closed short ends;a medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament; anda syringe that is configured to withdraw a portion of the liquid medicament from the dose container via an internal needle held by the dose cartridge that longitudinally translates along a fixed path to pierce the dose container at a location that is misaligned with a longitudinally extending centerline of the dose container, then engage a separate injection needle that is configured to inject the withdrawn portion in the syringe into a patient. 25. A device according to claim 24, wherein the internal needle resides inside of the dose cartridge and travels the fixed path between defined extended and retracted positions while inside the dose cartridge, wherein the internal needle resides proximate the injection needle and translates independently of the injection needle. 26. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall with a perimeter having a pair of substantially parallel spaced apart long sides that enclose an interior chamber and that merge into opposing first and second closed short ends;a medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament; anda first syringe that is adapted to be in fluid communication with the dose container while the dose container is held by the dose cartridge,wherein the dose container is configured to be pierced or punctured at first and second opposing end portions for extraction of the liquid medicament therein. 27. A device according to claim 26, further comprising a second syringe comprising sterile gas, and wherein the second syringe is adapted to be in fluid communication with the dose container at an opposing end of the dose container from the first syringe while the dose container is held in the dose cartridge whereby the gas pushes the liquid out of the dose container into the first syringe. 28. A device according to claim 27, wherein the cartridge further comprises at least one luer-lock configured to releasably engage at least one of the first and second syringes. 29. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall that encloses an interior chamber with opposing first and second closed ends; anda medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament,wherein the dose cartridge comprises a stepped fixed volume dispensing mechanism that includes a manually depressible plunger that communicates with a pressing member, the pressing member residing outside and in abutting contact with the dose container outer wall, wherein the stepped fixed volume dispensing mechanism slidably advances the pressing member fixed different distances in the cartridge to dispense a plurality of fixed amounts of the liquid medicament from the dose container, andwherein the pressing member comprises a roller, and wherein the plunger is in communication with the roller and a roller guide and a ratchet held in the cartridge, wherein the roller guide and ratchet cooperate to keep the roller in a forward location in the dose cartridge even when the plunger translates rearward, and wherein the plunger causes the roller to translate longitudinally to depress the compressible outer wall of the dose container to force the liquid medicament out of the dose container. 30. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall that encloses an interior chamber with opposing first and second closed ends; anda medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament,wherein the dose cartridge comprises a stepped fixed volume dispensing mechanism that includes a manually depressible plunger that communicates with a pressing member, the pressing member residing outside and in abutting contact with the dose container outer wall, wherein the stepped fixed volume dispensing mechanism slidably advances the pressing member fixed different distances in the cartridge to dispense a plurality of fixed amounts of the liquid medicament from the dose container, andwherein the pressing member comprises a roller with a curved inner surface that faces the dose container outer wall. 31. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall with a perimeter having a pair of substantially parallel spaced apart long sides that enclose an interior chamber and that merge into opposing first and second closed short ends; anda medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament;wherein the dose cartridge comprises a stepped fixed volume dispensing mechanism that includes a manually depressible plunger that communicates with a pressing member, the pressing member residing outside and in abutting contact with the dose container outer wall, wherein the dispensing mechanism slidably advances the pressing member fixed different distances in the cartridge to dispense a plurality of fixed amounts of the liquid medicament from the dose container, andwherein the dose cartridge comprises a replaceable needle interface comprising a needle luer-lock member directly attached to one end portion of the dose cartridge and is configured to releasably accept a plurality of different needles to extend adjacent to the one end portion of the dose cartridge. 32. A medicament device, comprising: a sealed medicament dose container having a substantially tubular body comprising a medicament that is stored frozen, then thawed into a liquid prior to administration, wherein the dose container has a longitudinally extending compressible outer wall that encloses an interior chamber with opposing first and second closed ends; anda medicament dose cartridge configured and sized to snugly hold the dose container therein during extraction of the liquid medicament, wherein the dose cartridge comprises a first end portion having an internal needle that does not contact a patient and is held in a non-use retracted position inside the dose cartridge during storage and is configured to translate along a fixed path inside the dose cartridge from the non-use retracted position to an extraction position whereby the internal needle pierces the dose container and is in fluid communication with the liquid medicament during extraction of the medicament,wherein the sealed dose container is held in a sealed state enclosing the medicament that is stored frozen, then thawed into a liquid prior to administration and in the sealed state the sealed dose container is devoid of movable internal components that force the medicament out of the dose container, and wherein the dose cartridge first end portion is adapted to slidably receive a syringe in a manner that places the syringe in fluid communication with the internal needle to allow a dose amount of the medicament to be withdrawn by the internal needle and directed into the syringe,wherein the first end of the dose cartridge further comprises an outwardly extending syringe attachment neck with an internal dam that defines a fluid barrier upstream of the dose container, wherein the internal needle resides between the dose container and the neck inside the dose cartridge, and wherein, in position, the syringe disengages the dam to be in fluid communication with the internal needle and the liquid medicament in the dose container. 33. A dose medicament transfer and/or delivery device, comprising: a dose container comprising an elongate body with a medicament and a compressible longitudinally extending outer wall, wherein the dose container with medicament is adapted to be stored frozen, and wherein the medicament is configured to be in liquid form proximate in time to delivery to a patient;a cartridge configured to hold the dose container therein; anda plunger in communication with a liquid medicament expulsion system in the cartridge configured to serially expel fixed volumes of liquid medicament from the dose container, wherein the plunger is a manually depressible plunger, wherein the liquid medicament expulsion system comprises a guide rod that engages the plunger, the guide rod having notches, and a pressing mechanism that cooperates with the guide rod and resides outside of and in abutting contact with the dose container outer wall and is configured to slidably advance fixed incremental distances about a length of the dose container in the cartridge to serially expel the fixed volumes of liquid medicament,wherein the plunger is in communication with a roller and a spring, a roller guide and a ratchet held in the cartridge associated with the liquid medicament expulsion system, wherein the spring, roller guide and ratchet cooperate to keep the roller in a forward location in the dose cartridge even when the plunger translates rearward, and wherein the plunger causes the roller to move relative to the roller guide. 34. A device according to claim 33, wherein the dose container elongate body has a planar bottom and at least one planar longitudinally extending wing extending from an outer edge of the body, wherein the expulsion system pressing mechanism comprises a roller with a roller guide that is configured to axially travel from a first end portion of the cartridge toward a second end portion of the cartridge. 35. A device according to claim 33, further comprising a one-way valve in communication with the liquid medicament expulsion system. 36. A dose medicament transfer and/or delivery device, comprising: a dose container comprising an elongate body with a medicament and a compressible longitudinally extending outer wall, wherein the dose container with medicament is adapted to be stored frozen, and wherein the medicament is configured to be in liquid form proximate in time to delivery to a patient;a cartridge configured to hold the dose container therein;a manually depressible plunger in communication with a liquid medicament expulsion system in the cartridge configured to serially expel fixed volumes of liquid medicament from the dose container, wherein the liquid medicament expulsion system comprises a press mechanism that resides outside of and in abutting contact with the dose container outer wall and is configured to slidably advance fixed incremental distances about a length of the dose container in the cartridge to serially expel the fixed volumes of liquid medicament; andan axially translating internal needle held a distance inside the dose cartridge spaced apart from an outer edge portion thereof and configured to travel a fixed path between a retracted home position and an extended position, the device further comprising a patient injection needle directly attached to the dose cartridge and extending outwardly therefrom, wherein the axially translating internal needle is configured to advance to enter the dose container inside the cartridge, and wherein the axially translating internal needle is held inside the cartridge and does not contact the patient during administration of the liquid medicament via the patient injection needle. 37. A device according to claim 36, wherein the axially translating internal needle is configured to be in fluid communication with the dose container to direct liquid medicament to exit therethrough to a channel in the cartridge upstream of the patient injection needle and downstream of the axially translating internal needle to the patient injection needle attached thereto. 38. A device according to claim 37, wherein the axially translating internal needle resides a distance inside the dose cartridge but is proximate the injection needle, and wherein the axially translating internal needle translates independently of the patient injection needle. 39. A device according to claim 36, wherein the axially translating internal needle is configured to be in fluid communication with the opened dose container to direct liquid medicament to exit therethrough to a channel in the cartridge that resides beyond the axially translating internal needle then to an external syringe attached thereto. 40. A device according to any one of claims 1-5, 7-30, 31, 16-23, 33, 34 or 36-35, wherein the liquid medicament comprises a vaccine. 41. A device according to any one of claims 1-5, 7-30, 31, 16-23, 33, 34 or 36-35, wherein the liquid medicament comprises cells. 42. A kit for delivering a liquid medicament, comprising: a syringe of sterile gas;a dose container comprising liquid medicament, wherein the dose container is a unitary sealed body with opposing first and second closed ends held in a sealed state enclosing the liquid medicament and in the sealed state the sealed dose container is devoid of movable internal components; anda cartridge sized and configured to snugly hold the dose container therein, wherein, in use, the syringe of sterile gas is configured to cooperate with the dose container to expel the liquid medicament from the dose container without expelling the sterile gas with the liquid medicament. 43. A method of expelling a liquid medicament from a dose container, comprising: providing a cartridge holding a sealed dose container having opposing first and second closed end portions with liquid medicament held inside the sealed dose container;attaching a syringe comprising sterile fluid therein to the cartridge;piercing a first end of the dose container;introducing the sterile fluid from the syringe into the first end portion of the dose container; thenpushing only the liquid medicament out of the second end portion of the dose container in response to the introducing step. 44. A method according to claim 43, wherein the sterile fluid is sterile air. 45. A method of delivering a liquid medicament, comprising: providing a container holding a liquid medicament in a frozen state;thawing the liquid medicament at a therapy administration site;heating a needle by inserting the needle into a needle channel of a heater attached to a cartridge that holds the container holding the liquid medicament at the administration site to a sterilization temperature;piercing the container with the needle after the heating step at the administration site; theninjecting the liquid medicament from the container into the subject after the thawing step. 46. A sealed elongate medicament container comprising a pharmaceutical medicament adapted to be cryogenically frozen then thawed into liquid in the sealed elongate medicament container prior to administration, wherein the sealed elongate medicament container has a unitary compressible body that is tubular with a perimeter defined by substantially parallel long sides merging into first and second opposing closed ends defined by flat sealed edge portions and is configured to be pierced by a needle at an extraction location that is spaced apart from both closed ends, and wherein the container compressible body has sufficient rigidity to maintain its shape with and without liquid medicament held therein, wherein the sealed elongate medicament container comprises a primary elongate lumen having (i) a substantially constant width throughout the elongate medicament container that holds the medicament and (ii) a secondary elongate lumen that (a) is parallel to and residing over an exterior long side of the sealed container or (b) angularly rises above an outer wall of the tubular container proximate an end portion of the tubular container, wherein the secondary elongate lumen is in fluid isolation from the primary lumen and seals an external surface of the primary lumen prior to extraction of the medicament from the primary lumen to define a sterile extraction surface, and wherein the secondary elongate lumen has a smaller cross-sectional area than the primary elongate lumen. 47. A container according to claim 46, wherein the sealed elongate medicament container has a body, when held in a non-compressed state, that has a substantially planar upper or lower outer surface that extends substantially over an entire length of the medicament container body, and wherein the body has a cross-sectional outer perimeter profile shape with a substantially concave portion merging into the substantially planar outer surface. 48. A container according to claim 46, wherein the long sides of the sealed elongate medicament container comprises first and second longitudinally extending substantially planar wings that extend outwardly off long sides of the elongate medicament container, and wherein the short sides define the opposing ends of the container. 49. A container according to claim 48, further comprising dose data indicia directly on at least one of the wings including (i) a patient specific identifier or a patient name or (ii) a patient specific identifier and a patient name associated with the pharmaceutical medicament in the elongate medicament container. 50. A container according to claim 46, wherein the compressible body of the sealed elongate medicament container is extruded with a wall defining a lumen holding the pharmaceutical medicament therein, wherein the flat sealed edge portions of the compressible body are each formed by opposing sides of the wall thereat being pressed together and sealed, and wherein the sealed elongate medicament container wall has a thickness of about 1/16 inch and an outer diameter of about 3/16 of an inch. 51. A container according to claim 46, further comprising an integral axially extending elongate projection extending above or below a lumen holding the medicament. 52. A container according to claim 46, wherein the sealed elongate medicament container comprises a sterile extraction outer surface residing at the extraction location and the extraction location is closer to one of the closed ends of the container. 53. A container according to claim 52, further comprising a removable protectant member residing over a needle entry port residing on the sterile extraction surface. 54. A container according to claim 52, further comprising a radially outwardly projecting semi-circular member defining a secondary outer channel that resides over the sterile extraction surface and is sealably attached to a wall of a primary lumen, wherein the primary lumen holds the pharmaceutical medicament therein, and wherein the semi-circular member with the secondary outer channel is configured to protect sterility of the sterile extraction surface prior to extraction of the liquid pharmaceutical medicament from the elongate medicament container. 55. A container according to claim 46, wherein the sealed elongate medicament container and the pharmaceutical medicament therein are configured to be held at one or more ultra-low temperatures of below about −40 degrees Celsius. 56. A container according to claim 46, wherein the sealed elongate medicament container and the pharmaceutical medicament therein are held at between about −70 degrees Celsius to about −95 degrees Celsius for a least a portion of a storage period or during shipment or during at least a portion of a storage period and during shipment. 57. A container according to claim 46, wherein the sealed elongate medicament container and the pharmaceutical medicament therein are held at between about −120 degrees Celsius to about −196 degrees Celsius for a least a portion of a storage period or during shipment or during at least a portion of a storage period and during shipment. 58. A container according to claim 46, wherein the sealed elongate medicament container is single-use unit dose medicament container comprising one of the following: polyvinyl chloride (PVC), a Class VI, medical grade TPE tubing polypropylene, polyethylene, polycarbonate and polystyrene, and wherein the medicament container is configured for cryogenic storage. 59. A container according to claim 46, wherein the sealed elongate medicament container is a multi-dose medicament container, and wherein the compressible body comprises one of the following: polyvinyl chloride (PVC), a Class VI, medical grade TPE tubing, polypropylene, polyethylene, polycarbonate and polystyrene, and wherein the multi-dose medicament container is configured for cryogenic storage. 60. A container according to claim 46, wherein the extraction location is on an upper or lower surface of the container proximate one of the closed ends, and wherein the closed ends have substantially the same configuration. 61. A sealed elongate medicament container comprising a pharmaceutical medicament adapted to be cryogenically frozen then thawed into liquid in the sealed elongate medicament container prior to administration, wherein the sealed elongate medicament container has a unitary compressible body that is tubular with a perimeter defined by substantially parallel long sides merging into first and second opposing closed ends defined by flat sealed edge portions and is configured to be pierced by a needle at an extraction location that is spaced apart from both closed ends, and wherein the container compressible body has sufficient rigidity to maintain its shape with and without liquid medicament held therein, wherein the sealed elongate medicament container comprises a sterile extraction outer surface residing at the extraction location and the extraction location is closer to one of the closed ends of the container; and a film sealed to the elongate medicament container over the sterile extraction surface. 62. A method of transferring and/or delivering liquid medicament, comprising: storing a dose container with a liquid medicament sealably held therein at a temperature sufficient to hold the liquid medicament in a frozen state;thawing the frozen liquid medicament in the dose container at a dispensing site while sealed;pushing a plunger inward; andin response to the pushing step, serially activating or operating a dispensing system associated with a cartridge holding the dose container with the liquid medicament so that the plunger cooperates with a roller guide rod with longitudinally spaced apart notches to automatically cause a pressing member in communication therewith to advance in fixed incremental distances about a length of the dose container and outside of the dose container while the pressing member presses against a longitudinally extending outer wall of the dose container with sufficient force to compress the outer wall of the dose container to cause the liquid medicament to exit the dose container to serially provide a plurality of fixed volume amounts,wherein the pressing member comprises a roller, and wherein the serially activating or operating comprises moving the roller unidirectionally axially while pressing against the outer wall of the dose container, the roller having a plurality of serial forward stroke lengths caused by the plunger engaging the roller guide rod at successive spaced apart notched positions that define the exiting fixed volume amounts, wherein the roller rotates about a roll axis that extends outside the dose container in a direction that is substantially orthogonal to a longitudinally extending centerline of the dose container, and wherein the plunger is in communication with the roller and a ratchet held in the cartridge, and wherein the roller and ratchet cooperate to keep the roller in successive forward locations in the dose cartridge even when the plunger translates rearward.