Patent Publication Number: US-2023147715-A1

Title: System and method for safety syringe

Description:
The present application is a continuation of U.S. patent application Ser. No. 16/798,188 filed on Feb. 21, 2020 entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”, which claims priority to (1) U.S. Provisional Patent Application Ser. No. 62/809,369, filed on Feb. 22, 2019 under attorney docket number CM.30023.00, and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE” and (2) U.S. Provisional Patent Application Ser. No. 62/864,509, filed on Jun. 21, 2019 under attorney docket number CM.30026.00, and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE.” This application also includes subject matter similar to the subject matter described in the following co-owned U.S. patent applications: (3) U.S. Utility patent application Ser. No. 14/321,706, filed Jul. 1, 2014 under attorney docket number CM.20001.00 and entitled “SAFETY SYRINGE”; (4) U.S. Utility patent application Ser. No. 14/543,787, filed Nov. 17, 2014 under attorney docket number CM.20002.00 and entitled “SYSTEM AND METHOD FOR DRUG DELIVERY WITH A SAFETY SYRINGE”; (5) U.S. Utility patent application Ser. No. 14/696,342, filed Apr. 24, 2015 under attorney docket number CM.20003.00 and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”; (6) U.S. Utility patent application Ser. No. 15/801,239, filed on Nov. 1, 2017 under attorney docket number CM.20011.00 and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”; (7) U.S. Utility patent application Ser. No. 15/801,259, filed on Nov. 1, 2017 under attorney docket number CM.20012.00 and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”; ( 8 ) U.S. Utility patent application Ser. No. 15/801,281 filed on Nov. 1, 2017 under attorney docket number CM.20013.00 and entitled “CARTRIDGE SAFETY INJECTION SYSTEM AND METHODS”; (9) U.S. Utility patent application Ser. No. 15/801,304 filed on Nov. 1, 2017 under attorney docket number CM.20015.00 and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”; (10) U.S. Provisional Patent Application Ser. No. 62/682,381 filed on Jun. 8, 2018 under attorney docket number CM.30019.00 and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE”; and (11) U.S. Provisional Patent Application Ser. No. 62/729,880 filed on Sep. 11, 2018 under attorney docket number CM.30021.00 and entitled “SYSTEM AND METHOD FOR SAFETY SYRINGE.” The contents of the above-mentioned applications are fully incorporated herein by reference as though set forth in full. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to injection systems, devices, and processes for facilitating various levels of control over fluid infusion, and more particularly to systems and methods related to multiple chamber safety syringes in healthcare environments. 
     BACKGROUND 
     Millions of syringes, such as that depicted in  FIG.  1 A  ( 2 ), are consumed in healthcare environments every day. A typical syringe ( 2 ) comprises a tubular body ( 4 ), a plunger ( 6 ), and an injection needle ( 8 ). As shown in  FIG.  1 B , such a syringe ( 2 ) may be utilized not only to inject fluid into a patient, but also to withdraw or expel fluid out of or into a container such as a medicine bottle, vial, bag, or other drug containment system ( 10 ). Indeed, due to regulatory constraints in some countries such as the United States as well as sterility maintenance concerns, upon use of a medicine bottle ( 10 ) with a syringe ( 2 ) as shown in a particular patient&#39;s environment, such medicine bottle may only be utilized with a single patient and then must be disposed of—causing significant medical waste from bottle and remaining medicine disposal, and even contributing to periodic shortages of certain critical drugs. Referring to  FIG.  2 A , three Luer-type syringes ( 12 ) are depicted, each having a Luer fitting geometry ( 14 ) disposed distally, so that they may be coupled with other devices having similar mating geometry, such as the Luer manifold assembly ( 16 ) depicted in  FIG.  2 B . The Luer manifold assembly of  FIG.  2 B  may be used to administer liquid drugs to the patient intravenously with or without the use of an intravenous infusion bag. The Luer fittings ( 14 ) of the syringes of  FIG.  2 A  may be termed the “male” Luer fittings, while those of  FIG.  2 B  ( 18 ) may be termed the “female” Luer fittings; one of the Luer interfaces may be threaded (in which case the configuration may be referred to as a “Luer lock” configuration) so that the two sides may be coupled by relative rotation, which may be combined with compressive loading. In other words, in one Luer lock embodiment, rotation, possibly along with compression, may be utilized to engage threads within the male fitting ( 14 ) which are configured to engage a flange on the female fitting ( 18 ) and bring the devices together into a fluid-sealed coupling. In another embodiment, tapered interfacing geometries may be utilized to provide for a Luer engagement using compression without threads or rotation (such a configuration may be referred to as a “slip-on” or “conical” Luer configuration). While such Luer couplings are perceived to be relatively safe for operators, there is risk of medicine spilling/leaking and parts breakage during assembly of a Luer coupling. The use of needle injection configurations, on the other hand, carries with it the risk of a sharp needle contacting or stabbing a person or structure that is not desired. For this reason, so called “safety syringes” have been developed. 
     One embodiment of a safety syringe ( 20 ) is shown in  FIG.  3   , wherein a tubular shield member ( 22 ) is spring biased to cover the needle ( 8 ) when released from a locked position relative to the syringe body ( 4 ). Another embodiment of a safety syringe ( 24 ) is shown in  FIGS.  4 A- 4 B . With such a configuration, after full insertion of the plunger ( 6 ) relative to the syringe body ( 4 ), the retractable needle ( 26 ) is configured to retract ( 28 ,  26 ) back to a safe position within the tubular body ( 4 ), as shown in  FIG.  4 B . Such a configuration which is configured to collapse upon itself may be associated with blood spatter/aerosolization problems, the safe storage of pre-loaded energy which may possible malfunction and activate before desirable, loss of accuracy in giving full-dose injections due to residual dead space within the spring compression volume, and/or loss of retraction velocity control which may be associated with pain and patient anxiety. 
     Further complicating the syringe marketplace is an increasing demand for prefilled syringe assemblies such as those depicted in  FIGS.  5 A and  5 B , which generally comprise a syringe body, or “drug enclosure containment delivery system”, ( 34 ), a plunger tip, plug, or stopper ( 36 ), and a distal seal or cap ( 35 ) which may be fitted over a Luer type interface ( FIG.  5 A  shows the cap  35  in place;  FIG.  5 B  has the cap removed to illustrate the Luer interface  14 ). Liquid medicine may reside in the volume, or medicine reservoir, ( 40 ) between the distal seal and the distal end ( 37 ) of the plunger tip ( 36 ). The plunger tip ( 36 ) may comprise a standard butyl rubber material and may be coated, such as with a biocompatible lubricious coating (e.g., polytetrafluoroethylene (“PTFE”)), to facilitate preferred sealing and relative motion characteristics against the associated syringe body structure and material. The proximal end of the syringe body ( 34 ) in  FIG.  5 B  comprises a conventional integral syringe flange ( 38 ), which is formed integral to the material of the syringe body ( 34 ). The flange ( 38 ) is configured to extend radially from the syringe body ( 34 ) and may be configured to be a full circumference, or a partial circumference around the syringe body ( 34 ). A partial flange is known as a “clipped flange” while the other is known as a “full flange.” The flange is used to grasp the syringe with the fingers to provide support for pushing on the plunger to give the injection. The syringe body ( 34 ) preferably comprises a translucent material such as a glass or polymer. To form a contained volume within the chamber or reservoir ( 40 ), and to assist with expulsion of the associated fluid through the needle, a plunger tip ( 36 ) may be positioned within the syringe body ( 34 ). The syringe body ( 34 ) may define a substantially cylindrical shape (i.e., so that a plunger tip  36  having a circular cross-sectional shape may establish a seal against the syringe body ( 34 )), or be configured to have other cross-sectional shapes, such as an ellipse. 
     Such assemblies are desirable because they may be standardized and produced with precision in volume by the few manufacturers in the world who can afford to meet all of the continually changing regulations of the world for filling, packaging, and medicine/drug interfacing materials selection and component use. Such simple configurations, however, generally will not meet the new world standards for single-use, safety, auto-disabling, and anti-needle-stick. Thus certain suppliers have moved to more “vertical” solutions, such as that ( 41 ) featured in  FIG.  5 C , which attempts to meet all of the standards, or at least a portion thereof, with one solution; as a result of trying to meet these standards for many different scenarios, such products may have significant limitations (including some of those described above in reference to  FIGS.  3 - 4 B ) and relatively high inventory and utilization expenses. 
     In some cases, multi-component injection systems may mix injectable components (e.g., liquids, solid, and/or powders) before injection. Several multiple chamber injection systems configured to mix and injection multiple components are disclosed in U.S. Utility patent application Ser. No. 14/696,342, which was previously incorporated by reference herein. 
     Moreover, an increasing number of injectable liquids (e.g., medicines) have an additional requirement that two or more components are preferably injected serially (e.g., into a patient) within a short time (e.g., seconds) of each other. Multiple components can be injected serially using separate injection devices (e.g., pre-loaded syringes) or using the same injection device to serially draw the multiple components from separate open containers and serially inject them. However, such serial injection using separate injection devices or serially drawing and injecting the multiple components necessarily results in multiple needle insertions into a patient, and can be inaccurate and lead to loss of components. Further, serial injection using separate injection devices or serially drawing the multiple components into a syringe can lead to unnecessary exposure of a user to one or more uncapped needles. Moreover, serial injection using separate injection devices or serially drawing and injecting the multiple components can cause an unacceptable lag between injections of the multiple components. Several multiple chamber injection systems that address these serial injection issues are disclosed in U.S. Provisional Patent Application Ser. No. 62/682,381, which was previously incorporated by reference herein. 
     In addition, an increasing number of injectable liquids (e.g., medicines) have yet another requirement that time of exposure of the injectable liquid to metals (e.g., stainless steel of a needle) be minimized. Still another requirement is the desirability of systems suitable for patient self-injection. 
     It is also desirable to incorporate needle stick prevention technology into the injection system. The ability to retract the sharp end of the needle at least partially inside of the syringe protects the person giving the injection and the patient from inadvertent needle stick injuries. 
     There is a need for injection systems which address the shortcomings of currently-available configurations. In particular, there is a need for multiple chamber safety injection solutions which may utilize the existing and relatively well- controlled supply chain of conventionally delivered prefilled syringe assemblies such as those described in reference to  FIGS.  5 A and  5 B . 
     SUMMARY 
     Embodiments are directed to injection systems. In particular, the embodiments are directed to multiple chamber safe injection systems that move the needle into a protected configuration to minimize accidental user injury and contamination with used needles. 
     In one embodiment, a method for preparing a pre-filled multi-chamber injection system includes providing an injection system body, the injection system body defining an open proximal end, a body interior, and an open distal end. The method also includes introducing a first substance into a distal end of the body interior. The method further includes disposing a distal stopper member in the body interior through the open proximal end of the injection system body, the distal stopper member and the injection system body defining proximal and distal chambers in the body interior, wherein the first substance is disposed in the distal chamber. Moreover, the method includes introducing a second substance into the body interior. In addition, the method includes disposing a proximal stopper member in the body interior through the open proximal end of the injection system body, such that the proximal stopper member defines a proximal end of the proximal chamber, wherein the second substance is disposed in the proximal chamber. The method also includes inserting an elongate member at least partially into the body interior, the elongate member having a plurality of flow channels for fluidly coupling the proximal and distal chambers and a proximal end configured to penetrate the distal stopper member. The method further includes coupling a plunger member to the proximal stopper member. 
     In one or more embodiments, introducing the first substance into the distal end of the body interior includes introducing a liquid into the distal end of the body interior and lyophilizing the liquid. Introducing the first substance into the distal end of the body interior may include introducing a powder or solid into the distal end of the body interior. The method may include disposing the injection system body in a rack in a first configuration before disposing the distal stopper member in the body interior, where, when the injection system body is in the first configuration, the distal end of the injection system body is pointed in a downward direction. The method may also include turning the injection system body in the rack to a second configuration before introducing the first substance into the distal chamber through the open distal end, where, when the injection system body is in the first configuration, the proximal end of the injection system body is pointed in a downward direction. The method may include returning the injection system body in the rack to the first configuration before introducing a second substance into the body interior and disposing the proximal stopper member in the body. 
     In one or more embodiments, the rack includes a feature to hold the injection method body in the first and second configurations in the rack. The distal stopper member may include a funnel therein, the method further including the funnel guiding the needle proximal end to a center of the distal stopper member. The funnel may include a U-shaped retaining member/detent. The needle proximal end may include a 3D arrowhead shape, the method further including the 3D arrowhead interfering with the U-shaped retaining member/detent to temporarily prevent distal movement of the distal stopper member. The method may include lyophilizing the first substance in distal chamber before coupling the needle hub assembly to the distal end of the injection system body. 
     In one or more embodiments, the method includes utilizing a pressure differential on proximal and distal sides of the proximal stopper member to insert the proximal stopper member into the body interior through the open proximal end of the injection system body. The method may include maintaining a vacuum in the proximal chamber during insertion of the proximal stopper member into the body interior through the open proximal end of the injection system body. The method may include disposing the proximal stopper member above the open proximal end of the injection system body before inserting the proximal stopper member into the body interior. The method may include disposing a tube adjacent the proximal stopper member such that the proximal chamber is fluidly coupled to an atmosphere during insertion of the proximal stopper member into the body interior through the open proximal end of the injection system body. The method may include maintaining a vacuum in the distal chamber during the method. The method may include performing one or more steps of the method in a vacuum. 
     In one or more embodiments, the method includes coupling a flange to the injection system body such that the flange is preventing from moving along a longitudinal axis and the plunger is moveable on the longitudinal axis relative to the flange. The method may include coupling the plunger to the proximal stopper member to facilitate movement of the proximal stopper member along the longitudinal axis. The injection system body, the needle hub assembly, and the proximal and distal stopper members may be pre-sterilized. The method may include preparing a plurality of pre-filled multi-chamber injection systems. The method may include introducing a third substance into the body interior through the open proximal end, and disposing a second proximal stopper member in the body interior through the open proximal end of the injection system body, such that the second proximal stopper member defines a proximal end of a second proximal chamber, where the third substance is disposed in the second proximal chamber. 
     In one embodiment, a method for preparing a pre-filled multi-chamber injection system includes disposing an injection system body (syringe/cartridge) in a rack in a first configuration, the injection system body defining an open proximal end, a body interior, and an open distal end, where, when the injection system body is in the first configuration, the distal end of the injection system body is pointed in a downward direction. The method also includes disposing a distal stopper member in the body interior through the open proximal end of the injection system body, the distal stopper member and the injection system body defining proximal and distal chambers in the body interior. The method further includes turning the injection system body in the rack to a second configuration, in which the proximal end of the injection system body is pointed in the downward direction. Moreover, the method includes introducing a first substance into the distal chamber through the open distal end. In addition, the method includes coupling a needle hub assembly to the distal end of the injection system body, the needle hub assembly including a needle having a needle proximal end, such that the needle proximal end interferes with the distal stopper member to temporarily prevent distal movement of the distal stopper member. The method also includes returning the injection system body in the rack to the first configuration. The method further includes introducing a second substance into the body interior through the open proximal end. Moreover, the method includes disposing a proximal stopper member in the body interior through the open proximal end of the injection system body, such that the proximal stopper member defines a proximal end of the proximal chamber, where the second substance is disposed in the proximal chamber. 
     In another embodiment, a method for preparing a pre-filled multi-chamber injection system includes coupling a needle hub assembly to an injection system body (syringe/cartridge), the needle hub assembly including a needle having a needle proximal end, and the injection system body defining an open proximal end, a body interior, and a distal end closed by the needle hub assembly. The method also includes disposing the injection system body in a rack in a first configuration, where, when the injection system body is in the first configuration, the distal end of the injection system body is pointed in a downward direction. The method further includes introducing a first substance into the body interior through the open proximal end. Moreover, the method includes disposing a distal stopper member in the body interior through the open proximal end of the injection system body, the distal stopper member and the injection system body defining proximal and distal chambers in the body interior, such that the needle proximal end interferes with the distal stopper member to temporarily prevent distal movement of the distal stopper member, where the first substance is disposed in the distal chamber. In addition, the method includes introducing a second substance into the syringe interior through the open proximal end. The method also includes disposing a proximal stopper member in the body interior through the open proximal end of the injection system body, such that the proximal stopper member defines a proximal end of the proximal distal chamber, where the second substance is disposed in the proximal chamber. 
     In still another embodiment, a method for preparing a pre-filled multi-chamber cartridge includes disposing a cartridge body in a rack in a first configuration, the cartridge body defining an open proximal end, a body interior, and an open distal end. When the cartridge body is in the first configuration, the distal end of the cartridge body is pointed in a downward direction. The method also includes disposing a distal stopper member in the body interior through the open proximal end of the cartridge body, the distal stopper member and the cartridge body defining proximal and distal chambers in the body interior. The method further includes turning the cartridge body in the rack to a second configuration, in which the proximal end of the cartridge body is pointed in the downward direction. Moreover, the method includes introducing a first substance into the distal chamber through the open distal end. In addition, the method includes optionally coupling a cartridge cap to the distal end of the cartridge body. The method also includes coupling a needle hub assembly to the distal end of the cartridge body over the cartridge cap, the needle hub assembly including a needle having a needle proximal end, such that the needle proximal end interferes with the distal stopper member to temporarily prevent distal movement of the distal stopper member. The method further includes returning the cartridge body in the rack to the first configuration. Moreover, the method includes introducing a second substance into the body interior through the open proximal end. In addition, the method includes disposing a proximal stopper member in the body interior through the open proximal end of the cartridge body, such that the proximal stopper member defines a proximal end of the proximal chamber, where the second substance is disposed in the proximal chamber. 
     In yet another embodiment, a method for preparing a pre-filled multi-chamber cartridge includes optionally coupling a cartridge cap to a cartridge body, the cartridge body defining an open proximal end, a body interior, and a distal end closed by the cartridge cap. The method also includes coupling a needle hub assembly to the distal end of the cartridge body over the cartridge cap, the needle hub assembly including a needle having a needle proximal end. The method further includes disposing the cartridge body in a rack in a first configuration, where, when the cartridge body is in the first configuration, the distal end of the cartridge body is pointed in a downward direction. Moreover, the method includes introducing a first substance into the body interior through the open proximal end. In addition, the method includes disposing a distal stopper member in the body interior through the open proximal end of the cartridge body, the distal stopper member and the cartridge body defining proximal and distal chambers in the body interior, such that the needle proximal end interferes with the distal stopper member to temporarily prevent distal movement of the distal stopper member, where the first substance is disposed in the distal chamber. The method also includes introducing a second substance into the syringe interior through the open proximal end. The method further includes disposing a proximal stopper member in the body interior through the open proximal end of the cartridge body, such that the proximal stopper member defines a proximal end of the proximal chamber, where the second substance is disposed in the proximal chamber. 
     In another embodiment, a method for preparing a pre-filled multi-chamber cartridge includes optionally coupling a cartridge cap to a cartridge body, the cartridge body defining an open proximal end, a body interior, and a distal end closed by the cartridge cap. The method also includes disposing the cartridge body in a rack in a first configuration, where, when the cartridge body is in the first configuration, the distal end of the cartridge body is pointed in a downward direction. The method further includes introducing a first substance into the body interior through the open proximal end. Moreover, the method includes disposing a distal stopper member in the body interior through the open proximal end of the cartridge body, the distal stopper member and the cartridge body defining proximal and distal chambers in the body interior, such that the needle proximal end interferes with the distal stopper member to temporarily prevent distal movement of the distal stopper member, where the first substance is disposed in the distal chamber. In addition, the method includes coupling a needle hub assembly to the distal end of the cartridge body over the cartridge cap, the needle hub assembly including a needle having a needle proximal end, such that the needle proximal end pierces the cartridge cap. The method also includes introducing a second substance into the syringe interior through the open proximal end. The method further includes disposing a proximal stopper member in the body interior through the open proximal end of the cartridge body, such that the proximal stopper member defines a proximal end of the proximal chamber, where the second substance is disposed in the proximal chamber. 
     In still another embodiment, a method for preparing a pre-filled multi-chamber cartridge includes disposing a cartridge body in a rack in a first configuration, the cartridge body defining an open proximal end, a body interior, and an open distal end. When the cartridge body is in the first configuration, the distal end of the cartridge body is pointed in a downward direction. The method also includes disposing a distal stopper member in the body interior through the open proximal end of the cartridge body, the distal stopper member and the cartridge body defining proximal and distal chambers in the body interior. The method further includes turning the cartridge body in the rack to a second configuration, in which the proximal end of the cartridge body is pointed in the downward direction. Moreover, the method includes introducing a first substance into the distal chamber through the open distal end. In addition, the method includes coupling a cartridge cap to the distal end of the cartridge body, the cartridge cap including a transfer tube, such that the transfer tube interferes with the distal stopper member to temporarily prevent distal movement of the distal stopper member. The method also includes returning the cartridge body in the rack to the first configuration. The method further includes introducing a second substance into the body interior through the open proximal end. Moreover, the method includes disposing a proximal stopper member in the body interior through the open proximal end of the cartridge body, such that the proximal stopper member defines a proximal end of the proximal chamber, where the second substance is disposed in the proximal chamber. 
     In yet another embodiment, a method for preparing a pre-filled multi-chamber cartridge includes optionally coupling a cartridge cap to a cartridge body, the cartridge body defining an open proximal end, a body interior, and a distal end closed by the cartridge cap. The method also includes piercing the cartridge cap with a transfer tube. The method further includes disposing the cartridge body in a rack in a first configuration, where, when the cartridge body is in the first configuration, the distal end of the cartridge body is pointed in a downward direction. Moreover, the method includes introducing a first substance into the body interior through the open proximal end. In addition, the method includes disposing a distal stopper member in the body interior through the open proximal end of the cartridge body, the distal stopper member and the cartridge body defining proximal and distal chambers in the body interior, such that the transfer tube interferes with the distal stopper member to temporarily prevent distal movement of the distal stopper member, where the first substance is disposed in the distal chamber. The method also includes introducing a second substance into the syringe interior through the open proximal end. The method further includes disposing a proximal stopper member in the body interior through the open proximal end of the cartridge body, such that the proximal stopper member defines a proximal end of the proximal chamber, where the second substance is disposed in the proximal chamber. 
     In one or more embodiments, the method includes coupling a flange and a plunger member to the injection system body such that the flange is preventing from moving along a longitudinal axis and the plunger is moveable on the longitudinal axis. 
     In still another embodiment, an autoinjector system includes a disposable injection system (syringe/cartridge) and a reusable drive system. The disposable injection system includes an injection system body having proximal and distal ends, and an injection system body interior therebetween. The disposable injection system also includes a stopper member disposed in the injection system body interior. The disposable injection system further includes a plunger member coupled to the stopper member. Moreover, the disposable injection system includes a finger flange coupled to the injection system body at the proximal end thereof. In addition, the disposable injection system includes a needle hub assembly coupled to the injection system body at the distal end thereof. The disposable injection system also includes a rigid needle shield coupled to the needle hub assembly. The reusable drive system includes a drive system body having a drive system body interior. The disposable injection system also includes a plunger actuator/pusher to move the plunger member distally relative to the injection system body when the injection system is mounted in the drive system. The disposable injection system further includes a flange holder/carriage to move the injection system distally and/or proximally relative to the drive system body when the injection system is mounted in the drive system. 
     In one or more embodiments, the drive system includes a first motor to move the plunger actuator/pusher, a second motor to move the flange holder/carriage, a controller operatively coupled to the first and second motors, a display operatively coupled to the controller, and a sensor operative coupled to the controller. The sensor may be selected from the group consisting of an accelerometer, a contact sensor, a position sensor, a gyroscope, a thermometer, and a skin contact sensor. The drive system may include a plurality of sensors. 
     In yet another embodiment, an autoinjector system includes a disposable injection system (syringe/cartridge) and a reusable drive system. The disposable injection system includes an injection system body having proximal and distal ends, and an injection system body interior therebetween, The disposable injection system also includes first and second stopper members disposed in the injection system body interior, the first stopper member and the injection system body defining a first chamber, the first and second stopper members and the injection system body defining a second chamber. The disposable injection system further includes a plunger member coupled to the second stopper member. Moreover, the disposable injection system includes a finger flange coupled to the injection system body at the proximal end thereof. In addition, the disposable injection system includes a needle hub assembly coupled to the injection system body at the distal end thereof. The disposable injection system also includes a rigid needle shield coupled to the needle hub assembly. The reusable drive system includes a drive system body having a drive system body interior. The reusable drive system also includes a plunger actuator/pusher to move the plunger member distally relative to the injection system body when the injection system is mounted in the drive system. The reusable drive system further includes a flange holder/carriage to move the injection system distally and/or proximally relative to the drive system body when the injection system is mounted in the drive system. 
     In one or more embodiments, the drive system includes a first motor to move the plunger actuator/pusher, a second motor to move the flange holder/carriage, a controller operatively coupled to the first and second motors, a display operatively coupled to the controller, and a sensor operative coupled to the controller. The sensor may be selected from the group consisting of accelerometer, a contact sensor, a position sensor, a gyroscope, a thermometer, and a skin contact sensor. The drive system may include a plurality of sensors. 
     In another embodiment, a method for automatically mixing and injecting substances includes providing the autoinjector system described above with the injection system mounted in the drive system, and the plunger actuator/pusher and flange holder/carriage in a proximal first position. The method also includes the controller causing the first motor to move the plunger actuator and the plunger member and the second stopper member operatively coupled thereto distally relative to the injection system body to transfer a fluid from the second chamber to the first chamber to form an injectable medicine. The method further includes the controller causing the first motor to move the plunger actuator and the plunger member and the second stopper member operatively coupled thereto further distally relative to the injection system body to inject the injectable medicine through the needle hub assembly. 
     In one or more embodiments, the method includes the controller causing the display to render a message instructing a user to agitate the device to enhance mixing of the fluid with a powder in the first chamber to form the injectable medicine. The method may include the controller causing the display to render a message instructing the user to point the autoinjector system in an upward position and remove the rigid needle shield from the autoinjector system before the controller causes the first motor to move the plunger actuator and the plunger member and the second stopper member operatively coupled thereto further distally relative to the injection system body. The method may include the sensor detecting the upward position of the autoinjector system; and the controller causing the second motor to move the flange holder/carriage proximally relative to the drive system body to separate the rigid needle shield from the needle hub assembly only when the sensor detects the upward position of the autoinjector system. 
     In one or more embodiments, the method includes the controller causing the display to render a message instructing the user to position the autoinjector system in contact with a patient before the controller causes the first motor to move the plunger actuator and the plunger member and the second stopper member operatively coupled thereto further distally relative to the injection system body. The method may include the sensor detecting contact between the autoinjector system and the patient, and the controller causing the first motor to move the plunger actuator and the plunger member and the second stopper member operatively coupled thereto further distally relative to the injection system body only when the sensor detects the contact between the autoinjector system and the patient. The method may include the controller causing the display to render a message indicating an end of injection and instructing the user to remove the injection system after the controller causes the first motor to move the plunger actuator and the plunger member and the second stopper member operatively coupled thereto further distally relative to the injection system body. 
     In still another embodiment, a multiple chamber safe injection system includes a syringe body defining a syringe body interior and a distal coupling member at a distal end thereof. The system includes proximal and distal stopper members disposed in the syringe body interior, forming a proximal chamber between the proximal and distal stopper members and a distal chamber between the distal stopper member and the distal end of the syringe body. The system also includes a plunger member configured to be manually manipulated to insert the proximal stopper member relative to the syringe body. The system further includes a mix tube disposed in the syringe body interior. Moreover, the system includes a vent plug disposed at least partially in the distal coupling member and defining a plurality of channels configured to allow a gas to exit the syringe body interior while forming a liquid tight seal. 
     In yet another embodiment, an injection system includes a syringe body defining a proximal opening at a proximal end thereof and a distal needle interface at a distal end thereof. The system also includes proximal and distal stopper members disposed in the syringe body, forming a proximal drug chamber between the proximal and distal stopper members and a distal drug chamber between the distal stopper member and the distal end of the syringe body. The system further includes a plunger member configured to be manually manipulated to insert the proximal stopper member relative to the syringe body, where the plunger member has a smooth exterior surface. Moreover, the system includes a fluid conveying assembly. In addition, the system includes a finger flange including an anti-retraction mechanism. The anti-retraction mechanism has a brake tab configured to provide an opposing force to the plunger member to prevent proximal movement thereof relative to the brake tab, and a retention feature configured to maintain the anti-retraction mechanism in a recess in the finger flange. 
     In one or more embodiments, the finger flange also includes another recess configured to mount the finger flange on a flange of the syringe body. The anti-retraction mechanism may also include a plurality of fit tabs configured to reduce a tolerance between the recess and a dimension of the anti-retraction mechanism. The anti-retraction mechanism may be a metal clip. 
     In one or more embodiments, the brake tab is an elastic and self-energizing pawl. The brake tab may be disposed at an acute angle in a distal direction relative to a plane of the anti-retraction mechanism. The acute angle and an elasticity of the brake tab may increase a frictional force against the plunger member upon retraction in a proximal direction. The acute angle of the brake tab also creates a reaction force parallel to the plunger member, exerted by a sharp curved edge of the brake tab contacting the surface of the plunger member. This force also prevents the plunger member from moving in the proximal direction. The acute angle and an elasticity of the brake tab may cause the brake tab to exert an outward force through the anti-retraction mechanism to an inner wall of the finger flange when the plunger member is retracted in a proximal direction. 
     In one or more embodiments, the finger flange also includes an opening having an edge configured to interfere with and retain the anti-retraction mechanism in the recess. The anti-retraction mechanism may have a “C” or “O” shape. The anti-retraction mechanism may prevent removal of the plunger member from the syringe body after the plunger member has been inserted into the syringe body. The opposing force may include a frictional force and a reaction force. The brake tab may be configured to penetrate the smooth exterior surface of plunger member when the plunger member moves proximally relative to anti-retraction mechanism. 
     The aforementioned and other embodiments of the invention are described in the Detailed Description which follows. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing and other aspects of embodiments are described in further detail with reference to the accompanying drawings, in which the same elements in different figures are referred to by common reference numerals, wherein: 
         FIGS.  1 A to  5 C  illustrate various aspects of conventional injection syringe configurations. 
         FIGS.  6 A and  6 B  illustrate various aspects of syringe based dual chamber safe injection systems wherein a distal needle end/tip may be withdrawn into a protected configuration after use according to some embodiments. 
         FIGS.  7 A to  7 P  illustrate various aspects of syringe based dual chamber safe injection systems during steps in methods for mixing and injecting using same according to some embodiments. 
         FIGS.  8 A and  8 B  illustrate various aspects of syringe based dual chamber safe injection systems according to some embodiments. 
         FIGS.  9 A to  9 C  illustrate various aspects of a distal stopper member having a stopper bushing with a detent for use with syringe based dual chamber safe injection systems according to some embodiments. 
         FIGS.  10 A to  10 C  illustrate various aspects of a stopper member bushing with a detent for use with syringe based dual chamber safe injection systems according to some embodiments. 
         FIGS.  11 A to  11 C  illustrate various aspects of a detent for use with a stopper member bushing for use with syringe based dual chamber safe injection systems according to some embodiments. 
         FIGS.  12 A to  12 C  depict a rack containing a plurality of injection system/syringe bodies and stored in a container according to some embodiments. 
         FIG.  13    is a flow chart illustrating a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  14 A to  14 J  illustrate various steps in a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  15 A to  15 D  illustrate various aspects of a detent for use with a stopper member bushing for use with a multiple chamber safe injection system according to some embodiments. 
         FIGS.  16  and  16 A  illustrate an interaction between a detent and a needle proximal end according to some embodiments. 
         FIG.  17    depicts a rack containing a plurality of injection system/syringe bodies and stored in a container according to some embodiments. 
         FIG.  18    is a flow chart illustrating a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  19 A to  19 H  illustrate various steps in a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  20 A to  20 D  depict a rack containing a plurality of cartridge bodies and stored in a container according to some embodiments. 
         FIG.  21    is a flow chart illustrating a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  22 A to  22 J  illustrate various steps in a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  23 A and  23 B  depict various aspects of a cartridge cap for use with a multiple chamber safe injection system according to some embodiments. 
         FIGS.  24 A and  24 B  depict cartridge bodies for use with multiple chamber safe injection systems according to some embodiments. 
         FIG.  25    depicts a rack containing a plurality of cartridge bodies and stored in a container according to some embodiments. 
         FIG.  26    is a flow chart illustrating a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  27 A to  27 G  illustrate various steps in a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIG.  28    is a flow chart illustrating a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIGS.  29 A to  29 H  illustrate various steps in a method for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. 
         FIG.  30    depicts cartridge stoppers for use with multiple chamber safe injection systems according to some embodiments. 
         FIGS.  31 A to  31 H  illustrate various steps in a method for injecting a drug using an autoinjector according to some embodiments. 
         FIGS.  32 A to  32 J  illustrate various steps in a method for mixing drug components and injecting the mixed drug using an autoinjector according to some embodiments. 
         FIGS.  33  to  40    illustrate various steps in a method for mixing drug components and injecting the mixed drug using a syringe having a luer connector according to some embodiments. 
         FIGS.  41  to  47    illustrate various aspects of a multiple chamber safe injection system having a vent plug according to some embodiments. 
         FIG.  48    depicts a vent plug according to some embodiments. 
         FIGS.  41 A and  49  to  56    depict anti-retraction mechanisms according to some embodiments. 
     
    
    
     In order to better appreciate how to obtain the above-recited and other advantages and objects of various embodiments, a more detailed description of embodiments is provided with reference to the accompanying drawings. It should be noted that the drawings are not drawn to scale and that elements of similar structures or functions are represented by like reference numerals throughout. It will be understood that these drawings depict only certain illustrated embodiments and are not therefore to be considered limiting of scope of embodiments. 
     DETAILED DESCRIPTION OF ILLUSTRATED EMBODIMENTS 
     Exemplary Prefilled Dual Chamber Safe Injection Systems 
     Referring to  FIGS.  6 A and  6 B , a perspective and a longitudinal cross-section view of a prefilled dual chamber safe injection system ( 100 ) are shown, with a conventional off-the-shelf prefilled syringe body ( 34 ) with conventional proximal and distal stopper members ( 32 ,  36 ) disposed therein. The proximal and distal stopper members ( 32 ,  36 ) together with the syringe body ( 34 ) define proximal and distal chambers ( 40 ,  42 ). The proximal and distal stopper members ( 36 ,  37 ) occlude the proximal and distal ends of the proximal chamber ( 40 ). The distal stopper member ( 36 ) occludes a proximal end of the distal chamber ( 42 ). In some embodiments, the distal end of the proximal stopper member ( 32 ) and the proximal end of the distal stopper member ( 36 ) may be coated with a lubricious polymer coating (e.g., PTFE), the first and second polymer coatings of the proximal and distal stopper members ( 32 ,  36 ), together with the syringe body ( 34 ) define the proximal chamber ( 40 ). The lubricious polymer coating also serves to isolate the rubber of the proximal and distal stopper members ( 32 ,  36 ) from the second liquid ( 254 ). The proximal and distal stopper members ( 32 ,  36 ) may be oriented as shown in  FIGS.  6 A and  6 B  or the distal stopper ( 36 ) may be flipped so the lubricious coating faces the distal chamber ( 42 ) such that the first liquid ( 252 ) in the distal chamber ( 42 ) contacts the lubricious coating for storage. 
     A needle coupling assembly ( 606 ) is disposed at the distal end of the distal chamber ( 42 ) with a needle cover member ( 63 ) installed for storage. The dual chamber safe injection system facilitates sequential injection of a first liquid ( 252 ) from the distal chamber ( 42 ) followed by injection of a second liquid ( 254 ) from the proximal chamber subject to sequential insertion of a plunger assembly ( 44 ) relative to the syringe body ( 34 ) to various degrees by a user. The plunger assembly ( 44 ) includes the proximal stopper member ( 32 ), a plunger housing member ( 69 ) and a plunger manipulation interface ( 128 ). The first and second liquids located in the distal and proximal chambers ( 42 ,  40 ) respectively may be any liquid or gel, such as aqueous or oil based medicine solutions. 
     The dual chamber safe injection system ( 100 ) has a staked needle configuration wherein upon presentation to the user, a needle assembly, including a needle spine assembly (“needle”) ( 76 ) and a needle coupling assembly ( 606 ) are mounted in position ready for injection after removal of a needle cover member ( 63 ) which may comprise an elastomeric sealing material on its internal surface to interface with a needle distal end ( 78 ) and/or a distal housing portion during storage. Alternatively, the needle cover member ( 63 ) may comprise a vent (not shown) for allowing pressure resulting from the transfer of the liquids ( 252 ,  254 ) to escape from inside the syringe body ( 34 ) while preventing contamination from entering the syringe body ( 34 ). While, the staked needle is depicted as mounted in position, the staked needle may be removably coupled to the syringe body ( 34 ) using a Luer slip or a Luer lock interface (not shown), with the proximal end ( 50 ) of the needle member extending through the Luer interface and into the distal chamber ( 42 ). Alternatively, the needle may be fixedly or removably mounted to the flange on a cartridge body instead of a syringe. Such cartridge injection systems are disclosed in U.S. Utility Patent Application Serial Number  15 / 801 , 281 , which was previously incorporated by reference herein. In the embodiments depicted in  FIGS.  6 A and  6 B , a significant portion of the safe needle retraction hardware resides within a plunger housing. 
     Referring to  FIGS.  7 A- 7 L , various aspects of configurations designed to facilitate injection of multi-part medications and retractions of a needle into a syringe body are illustrated, wherein two or more medication components are combined to form an injection combination or solution shortly before delivery into the patient. In one variation, a liquid first medicine component/diluent ( 252 ) may be combined with a substantially non-liquid second medicine component ( 254 ), such as a powdered and/or a solid (e.g., compressed powder) form, of a drug agent, such as a freeze-dried or lyophilized drug component, shortly before injection. The second medicine component ( 254 ) may be comprised of powdered medicine formed into a generally solid form. The solid form may be created by compressing powder and/or by using a binder material. This solid medicine component may be configured to be, cylindrical, tubular, spherical, a polygon, and/or or a toroidal shape. The solid medicine ( 254 ) may be placed inside the distal medicine chamber ( 42 ) during and/or in place of the lyophilization step. The solid form of the second medicine component ( 254 ) is configured to dissolve and/or disperse when contacted by liquid. The configurations described herein in reference to  FIGS.  7 A- 7 L  relate to dual-chamber configurations, wherein two or more chambers within the same syringe body ( 34 ) are utilized to carry, mix, and inject an injection solution. 
     Referring to  FIG.  7 A and  7 B , proximal and distal medicine chambers ( 40 ,  42 ) are formed by a distal stopper member ( 36 ) in between two portions of the interior of a syringe body ( 34 ), such that the distal medicine chamber ( 42 ) contains an air or gas gap, as well as a non-liquid medication ( 254 ); a proximal medicine chamber ( 40 ), on the opposite side of the distal stopper member ( 36 ) contains a liquid diluent ( 252 ), which is proximally contained by a proximal stopper member ( 32 ). The liquid diluent ( 252 ) is a first component of a medicine and the non-liquid medication ( 254 ) is a second component of the medicine. 
     Referring to  FIG.  7 C , and the associated cross sectional view in  FIG.  7 D , various components of a needle coupling assembly (here a so-called “staked” needle coupling assembly ( 606 ) is illustrated, but other needle assemblies as described below, including Luer-coupled as well as staked configurations, may be utilized). Lug features ( 258 ) are configured to assist with coupling the needle coupling assembly ( 606 ) to a needle cover member ( 63 ), as shown in  FIG.  7 A , for example. A small O-ring may be utilized as a sealing member ( 260 ) around the needle shaft, while a larger O-ring may be utilized as a sealing member ( 262 ) at the syringe body ( 34 )/needle coupling assembly ( 606 ) interface. Alternatively, the small O-ring ( 260 ) and the large O-ring ( 262 ) may be combined into a single seal that performs both of the O-ring sealing functions. Also, the small O-ring ( 260 ) may be used to seal both around the needle shaft and to the syringe body ( 34 ). 
     The needle includes a plurality (e.g., four) of proximal openings/ports ( 270 ) configured to allow for entry of a liquid diluent, to be expelled out of a more distally-located middle opening/aperture ( 266 ); a lumen plug ( 268 ) occludes the needle lumen to create the flow path from the proximal openings ( 270 ) to the middle opening ( 266 ) under conditions such as those described herein in reference to  FIG.  7 H . The needle also includes a distal opening ( 264 ) on the opposite side of the lumen plug ( 268 ) from the middle opening ( 266 ). The distal opening ( 264 ) is fluidly coupled to the needle distal end ( 48 ) through the needle to inject liquid into a patient. 
     Referring to  FIG.  7 E , a proximal harpoon interface ( 84 ) is configured to serially penetrate proximal and distal stopper members ( 32 ,  36 ), and couple with a coupling feature (such as a needle retention feature are illustrated, for example, in  FIGS.  7 N and  7 P , element  712 ) in the plunger rod.  FIG.  7 F  illustrates a spike style harpoon coupling interface ( 85 ) that is configured to serially pierce both proximal and distal stopper members ( 32 ,  36 ) and couple with a coupling feature in the plunger rod to retract the needle member at least partially into the plunger rod after the injection has been given to the patient. 
       FIGS.  7 A,  7 B, and  7 G- 7 P  illustrate a sequence of actions for an injection procedure utilizing a dual chamber safe injection system such as that described above. Referring to  FIGS.  7 A and  7 B , an injection assembly is in a stable configuration wherein it may be shipped or brought to an injection patient care scenario; a first drug component/liquid diluent ( 252 ) is isolated from a second non-liquid drug component ( 254 ), both within a syringe body on opposite sides of a distal stopper member ( 36 ). 
       FIGS.  7 G and  7 H  illustrate initial insertion movement of the plunger assembly ( 44 ), advancing the distal ( 36 ) and proximal ( 32 ) stopper members together relative to the syringe body ( 34 ). Referring to  FIG.  7 H , with advancement sufficient to stab the proximal end ( 50 ) of the needle assembly across the distal stopper member ( 36 ), a fluid pathway is formed between the two previously isolated chambers ( 40 ,  42 ) of the syringe body ( 34 ), such that the liquid first drug component ( 252 ) in the proximal medicine chamber ( 40 ) may flow into at least one of the proximal openings ( 270 ), through the transfer pipe ( 46 ), and exit the more distal middle opening ( 266 ), to reach the non-liquid second drug component ( 254 ) in the distal medicine chamber ( 42 ). 
       FIGS.  7 I and  7 J  illustrate that with further insertion until the stopper members ( 36 ,  32 ) are immediately adjacent each other, the liquid first drug component/diluent ( 252 ) has moved into the distal medicine chamber ( 42 ) to join the non-liquid second drug component ( 254 ).  FIGS.  7 K and  7 L  illustrate that with time and/or manual agitation, the liquid first drug component/diluent ( 252 ) and previously non-liquid second drug component ( 254 ) become mixed to form a mixed medication solution ( 272 ). 
     In some embodiment, especially with lyophilized non-liquid second drug components, the mixed medication solution ( 272 ) may be formed with minimal or no agitation or time passage. In another embodiment, especially with drugs which are held in suspension or emulsified drugs, vigorous shaking may be necessary to facilitate mixing. In the case of vigorous shaking it is useful to the user to be able to remove their thumb from the plunger manipulation interface ( 128 ). During transfer of liquid first medicine component ( 252 ) from the proximal to the distal medicine chambers ( 40 ,  42 ) pressure may build up in the distal medicine chamber ( 42 ). This pressure acts upon the proximal and distal stopper members ( 32 ,  36 ) to resist stopper motion. The pressure buildup may also move the stopper members ( 32 ,  36 ) and plunger manipulation interface ( 128 ) proximally if the user does not have their thumb restraining the plunger assembly ( 44 ). Mixed configuration latches or “mix clicks” in the plunger assembly ( 44 ) (depicted in  FIGS.  9 A and  9 B  and described below) may be utilized to provide resistance to plunger manipulation interface ( 128 ) motion due to pressure buildup and allow the user to release their thumb from the plunger manipulation interface ( 128 ) for shaking or mixing of the drug. The mix clicks may also provide an audible and/or tactile indication that the transfer of liquid first medicine component ( 252 ) has been completed. The distal medicine chamber ( 42 ) may also include an agitation device, which assists in mixing of the medicine components. 
     With the assembly ready for injection of the mixed solution ( 272 ), the needle cover member ( 63 ) may be removed and the patient may be injected with the exposed needle distal end ( 48 ) with depression/insertion of the plunger assembly ( 44 ) and associated stopper members ( 36 ,  32 ) as shown in  FIGS.  7 M and  7 N . Referring to  FIGS.  70  and  7 P , with full depression/insertion of the plunger assembly ( 44 ) and associated stopper members ( 32 ,  36 ), the sharp needle distal end/point ( 48 ) may automatically retract at least partially through the distal and proximal stopper members ( 36 ,  32 ) to a safe position within either the syringe body ( 34 ), the needle coupling assembly ( 606 ), or at least partially within the plunger assembly ( 44 ). Automatic retraction of the needle at least partially within the plunger is described in U.S. utility patent application Ser. No. 14/696,342, which was previously incorporated by reference herein. 
     Further details regarding multiple chamber injection systems (components, methods using same, etc.) are disclosed in U.S. Utility patent application Ser. No. 15/801,259, and U.S. Provisional Patent Application Ser. Nos. 62/682,381 and 62/729,880, which were all previously incorporated by reference herein. 
     Exemplary Distal Bushings with Detents in Dual Chamber Safe Injection Systems 
       FIGS.  8 A and  8 B  depict a prefilled dual chamber safe injection system ( 800 ) according to some embodiments. The system ( 800 ) includes a stopper bushing ( 810 ) having a detent ( 812 ) disposed therein (see  FIG.  8 B ). The detent ( 812 ) is configured to interact with the sharpened proximal end ( 884 ) of the needle spine assembly ( 876 ) and a shoulder ( 816 ) at the junction between the needle proximal end ( 850 ) and the needle joining member ( 883 ) to provide resistance to distal movement of the distal stopper member ( 836 ) relative to the needle spine assembly ( 876 ) (see  FIG.  8 B ). 
     The interaction between the detent ( 812 ) and the proximal end ( 884 ) maintains the distal stopper member ( 836 ) in a ready to use position during storage and transport, such as the configuration depicted in  FIGS.  8 A and  8 B . This interaction will maintain the position of the distal stopper member ( 836 ) even with a vacuum or partial vacuum (e.g. for the lyophilized component) in the distal chamber ( 842 ). Without the detent ( 812 ) and with a vacuum in the distal chamber ( 842 ), the distal stopper member ( 836 ) will eventually move distally relative to the needle spine assembly ( 876 ) and be penetrated thereby. This would render the system unusable. 
     The interaction between the detent ( 812 ) and the shoulder ( 816 ) maintains the distal stopper member ( 836 ) in a transfer position during transfer of the liquid from the proximal chamber ( 840 ) to the distal chamber ( 842 ). This interaction allows the user to apply a wider range of force to the plunger member to transfer the liquid while minimizing the risk of premature movement of the distal stopper member ( 836 ). 
       FIGS.  9 A to  9 C  depict the interactions between the detent ( 812 ) and the sharpened proximal end ( 884 ) of the needle spine assembly ( 876 ) and a shoulder ( 816 ) on the needle spine assembly ( 876 ) in the prefilled dual chamber safe injection system ( 800 ) depicted in  FIGS.  8 A and  8 B .  FIG.  9 A  shows a distal stopper member ( 836 ) having a stopper bushing ( 810 ) with a detent ( 812 ) and defining an alignment funnel ( 814 ). In  FIG.  9 A  the alignment funnel ( 814 ) guides a proximal end ( 884 ) of the needle spine assembly ( 876 ) into positioned adjacent the detent ( 812 ). 
       FIG.  9 B  shows the storage/transport configuration of the system ( 800 ). In this configuration, the sharpened proximal end ( 884 ) of the needle spine assembly ( 876 ) is disposed adjacent to and partially within the detent ( 812 ). Various properties of the proximal end ( 884 ) and the detent ( 812 ) (e.g., geometric, material, etc.) can be modified to modulate the force required to push the proximal end ( 884 ) past the detent ( 812 ). These properties are described in detail below. In one embodiment, the force required to push the proximal end ( 884 ) past the detent ( 812 ) is from about 2 pounds to about 5 pounds. As described above, even with a vacuum or partial vacuum in the distal chamber ( 842 ) urging the distal stopper member ( 836 ) in a distal direction, the interaction between the proximal end ( 884 ) and the detent ( 812 ) prevents premature movement of the distal stopper member ( 836 ) relative to the needle spine assembly ( 876 ). This allows the prefilled dual chamber system ( 800 ) to be stored while minimizing the risk of premature movement of the distal stopper member ( 836 ), which can render the system ( 800 ) unusable. 
       FIG.  9 C  shows the transfer configuration of the system ( 800 ). In this configuration, the distal stopper member ( 836 ) has been pushed distally past the sharpened proximal end ( 884 ) of the needle spine assembly ( 876 ) by user provided force on the plunger member. The proximal openings ( 885 ) are disposed in the proximal chamber ( 840 ) allowing liquid to transfer from the proximal chamber ( 840 ) to the distal chamber ( 842 ). While a vacuum in the distal chamber ( 842 ) withdraw the liquid out of the proximal chamber ( 840 ), user generated force applied to the proximal stopper member ( 832 ) via the plunger member will assist the liquid transfer. In this configuration, a shoulder ( 816 ) on the needle spine assembly ( 876 ) is disposed adjacent to the detent ( 812 ). Various properties of the shoulder ( 816 ) and the detent ( 812 ) (e.g., geometric, material, etc.) can be modified to modulate the force required to push the shoulder ( 816 ) past the detent ( 812 ). These properties are described in detail below. In one embodiment, the force required to push the shoulder ( 816 ) past the detent ( 812 ) is from about 2 pounds to about 5 pounds. The shoulder is formed at the joint between the needle proximal end ( 850 ) and the needle joining member ( 883 ). While the interaction between the shoulder ( 816 ) and the detent ( 812 ) holds the system ( 800 ) in the transfer configuration depicted in  FIG.  9 C , pressure applied to the plunger member will aid liquid transfer from the proximal chamber ( 840 ) to the distal chamber ( 842 ). The force required to overcome the interference between the shoulder ( 816 ) and the detent ( 812 ) provides more latitude for a user to press the plunger member to aid in the liquid transfer. This increases the chances of complete liquid transfer. 
       FIGS.  10 A to  10 C  depict a stopper bushing ( 810 ) for use with the prefilled dual chamber safe injection system ( 800 ) depicted in  FIGS.  8 A and  8 B . The stopper bushing ( 810 ) has a detent ( 812 ) inserted into a slot in the bushing ( 810 ) along an axis orthogonal to the longitudinal axis of the needle spine assembly. As shown in  FIG.  10 C , the detent may be made of a bent wire having a “U” shape. 
       FIGS.  11 A to  11 C  show detents ( 1112 ,  1112 ′) for use with stopper bushings of prefilled dual chamber safe injection systems according to some embodiments. The detents ( 1112 ,  1112 ′) are formed from a sheet of metallic material, and thus have a flat cross-section. The detents ( 1112 ,  1112 ′) all have a “U” shape and include a notch ( 1118 ) configured to receive a round shape, such as those on sharpened proximal ends and shoulders of the needle spine assemblies. The detent ( 1112 ′) depicted in  FIG.  11 B  includes a chamfered/baffled penetration surface ( 1120 ) around a circumference of the notch ( 1118 ) on the side of the detent ( 1112 ′) adjacent the sharpened proximal ends of the needle spine assemblies in the storage/transport configuration described above. The beveled penetration surface ( 1120 ) can be modified to modulate the amount of force required to penetrate the detent ( 1112 ′). 
       FIG.  11 C  depicts the sharpened proximal end ( 1184 ) of a needle spine assembly ( 1176 ) disposed in the notch ( 1118 ) of a detent ( 1112 ), such as in a storage/transport configuration. 
     In one embodiment, the resistance force provided by the detent ( 1112 ) as it slides over a sharpened proximal end ( 1184 ) of a needle spine assembly ( 1176 ) is variable. The detent ( 1112 ) resist penetration by the proximal end ( 1184 ) during storage (e.g., for several years). With the application of a predetermined amount of force by the user, the proximal end ( 1184 ) slides through the detent ( 1112 ). Then, the resistance force to movement of the needle spine assembly ( 1176 ) through the detent ( 1112 ) is minimal until the detent ( 1112 ) reaches the shoulder ( 816 , see  FIG.  9 C ). When the detent ( 1112 ) abuts the shoulder, resistance force increases to reliably stop the progress of the detent ( 1112 ) (and distal stopper member) relative to the needle ( 1176 ). After liquid transfer described above, the user applies another predetermined amount of force to push the detent ( 1112 ) will over the shoulder. After the shoulder is cleared, the friction from the interaction of the detent ( 1112 ) and the needle ( 1176 ) is minimal to facilitate giving the injection and needle retraction. 
     The predetermined amount of force can be modulated to accommodate a combination of the system function requirements and the aesthetic impression on the user. If the activation force is too low, it may work, but be too difficult for the user to apply the force lightly enough, and the user may overshoot. If the force is too high, the user may find that it is “too hard” to activate the system. Fortunately, the predetermined amount of force can be “tune” a range by modifying various component characteristics. 
     While the embodiments described above include dual chamber safety injection systems, the scope of the claims also include other multiple chamber safety injection systems. For multiple chamber safety injection systems with more than two chambers, more than two stopper members are inserted into an injection system body (e.g., syringe body, cartridge body, etc.) to define a corresponding number of chambers. 
     Exemplary Multiple Chamber Safe Injection System Manufacturing Methods 
     Injection System/Syringe Fill Distal Chamber from Front 
       FIGS.  12 A and  12 B  depict a rack  1210  containing a plurality of injection system/syringe bodies  1410  and stored in a container  1212 . The rack  1210  and the container  1212  are made from materials that are sterilizable. The container  1212  is closable with a seal  1214  ( FIG.  12 A ) to maintain the sterility of the rack  1210  and injection system/syringe bodies  1410  contained therein. 
       FIG.  12 C  depicts the rack  1210  removed from the container  1212  and one injection system/syringe body  1410  removed from the rack  1210 . The rack  1210  has a plurality of features (e.g., sleeves and/or flanges)  1216  to hold the injection system/syringe bodies  1410  in a first configuration in which the distal end of the injection system/syringe body  1410  is pointed in a generally downward direction (see  FIG.  14 A ). In some embodiments, the features  1216  are also configured to hold the injection system/syringe bodies  1410  in a second configuration in which the proximal end of the injection system/syringe body  1410  is pointed in a generally downward direction (see  FIG.  14 C ). 
       FIG.  13    depicts a method  1300  for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. Corresponding partially assembled components are depicted in  FIGS.  14 A to  14 J . 
     At  1310 , an injection system/syringe body  1410  is disposed in a rack in a first (downward) configuration as shown in  FIG.  14 A . The injection system/syringe body  1410  may be disposed in the rack by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  1312 , a distal stopper member  1414  is disposed in an interior  1412  of the injection system/syringe body  1410  as shown in  FIG.  14 B . The distal stopper member  1414  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The distal stopper member  1414  and the injection system/syringe body  1410  define proximal and distal chambers  1416 ,  1418  in the body interior  1412 . The distal stopper member  1414  may be positioned over an open proximal end of the injection system/syringe body  1410  to facilitate insertion of the distal stopper member  1414  into the body interior  1412 . 
     At  1314 , the injection system/syringe body  1410  is turned to a second (upward) configuration as shown in  FIG.  14 C . The injection system/syringe body  1410  may be repositioned in the rack after being turned to the second configuration. Injection system/syringe body  1410  may be turned and/or repositioned by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  1316 , a first substance  1420  is introduced into the distal chamber  1418  through the open distal end of the injection system/syringe body  1410  as shown in  FIG.  14 C . The first substance  1420  may be introduced directly through the opening at the distal end of the injection system/syringe body  1410 . In some embodiments, a tube may be inserted through the opening at the distal end of the injection system/syringe body  1410 , and the first substance  1420  may be introduced through the tube. The first substance  1420  may be a liquid, a solid (e.g., compressed powder), and/or a powder. In some embodiments where the first substance  1420  is a liquid, the first substance  1420  may be lyophilized in an optional step to form a powder as shown in  FIG.  14 D . 
     At  1318 , a needle hub assembly  1422  is coupled to the distal end of the injection system/syringe body  1410  as shown in  FIGS.  14 E and  14 F . The needle hub assembly  1422  includes a needle  1424  having a needle proximal end  1426 . The needle proximal end  1426  interferes with the distal stopper member  1414  to temporarily prevent distal movement of the distal stopper member  1414  relative to the injection system/syringe body  1410 . The needle hub assembly  1422  is coupled to the distal end of the injection system/syringe body  1410  by a user (e.g., using a tool) or by a mechanical device (e.g., robot). Alternatively, the injection system/syringe body  1410  may be closed with a luer cap as disclosed in  FIGS.  33 - 40    and described below. In this case the dual chamber system would be provided without a pre-attached needle. The transfer tube component may be pre-inserted into the syringe body or installed at the time of placing the luer cap. The user may attach a needle at the time of use by using a luer slip or luer lock connection method. 
     In some alternative embodiments, the injection system/syringe body  1410  may be supplied with a needle hub assembly  1422  or luer cap coupled thereto. In some embodiments, the coupled the injection system/syringe body  1410 , needle hub assembly  1422 , and/or luer cap may be pre-sterilized. In other embodiments, pre-sterilized components may be supplied and assembled at the time of filling. 
     Components of the distal stopper member  1414  that interfere with the needle proximal end  1426  are depicted in  FIGS.  15 A to  15 D and  16  to  16 A .  FIG.  15 A  depicts a U-shaped retaining member/detent  1428  and a bushing/funnel  1430 . After coupling the U-shaped retaining member/detent  1428  the bushing/funnel  1430 , the bushing/funnel  1430  is screwed into the stopper member  1414 .  FIGS.  16  and  16 A  depict the stage in the manufacturing process identified at  1318  and also shown in  FIG.  14 F . As shown in  FIG.  16 A , the needle proximal end  1426  has an enlarged portion that interferes with the U-shaped retaining member/detent  1428 . This interference increases the amount of force necessary to move the needle proximal end  1426  past the distal stopper member  1414 . The increased amount of force allows a vacuum to be present in the distal chamber  1418  of the injection system/syringe body  1410  without prematurely moving the needle proximal end  1426  past the distal stopper member  1414  during storage of the multiple chamber safe injection system. The bushing funnel  1430  guides the needle proximal end  1426  to the U-shaped retaining member/detent  1428  during assembly. 
     At  1320 , the injection system/syringe body  1410  is turned back to the first (downward) configuration as shown in  FIG.  14 G . The injection system/syringe body  1410  may be repositioned in the rack after being turned back to the first configuration. Injection system/syringe body  1410  may be turned and/or repositioned by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  1322 , a second substance  1432  is introduced into the proximal chamber  1416  through the open proximal end of the injection system/syringe body  1410  as shown in  FIG.  14 H . The second substance  1432  may be introduced directly through the opening at the proximal end of the injection system/syringe body  1410 . The second substance  1432  may be a liquid or another fluid. 
     At  1324 , a proximal stopper member  1434  is disposed in the interior  1412  of the injection system/syringe body  1410  as shown in  FIG.  141   . The proximal stopper member  1434  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The proximal stopper member  1434  closes the proximal chambers  1416  defined by the injection system/syringe body  1410  and the distal stopper member  1414 . The proximal stopper member  1434  may be positioned over an open proximal end of the injection system/syringe body  1410  to facilitate insertion of the proximal stopper member  1434  into the body interior  1412 . 
     A pressure differential on opposite sides of the proximal stopper member  1434  may be used to draw the proximal stopper member into the body interior  1412 . For instance, a vacuum maybe formed on the distal side of the proximal stopper member  1434 . In some embodiments, a small tube is disposed adjacent the proximal stopper member  1434  to release pressure that builds up as the proximal stopper member  1434  is inserted into the body interior  1412 . The small tube is removed after assembly. 
     In an optional step shown in  FIG.  14 J , a finger flange  1336  and a plunger member  1438  are coupled to the injection system/syringe body  1410 . The finger flange  1436  may be coupled to the injection system/syringe body  1410  such that it is prevented from moving along a longitudinal axis of the body  1410  (e.g., by snapping over a glass flange at the proximal end of the body  1410 ). The plunger member  1438  may be coupled to the injection system/syringe body  1410  such that it is movable along a longitudinal axis of the body  1410 . A distal end of the plunger member  1438  is also coupled to the proximal stopper member  1434  (e.g., using a threaded screw), such that movement of the plunger member  1438  relative to the injection system/syringe body  1410  moves the proximal stopper member  1434 . The finger flange  1436  and a plunger member  1438  may be coupled to the injection system/syringe body  1410  by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     Further details regarding the injection system/syringe body  1410 , the proximal and distal stopper members  1414 ,  1434 , the needle hub assembly  1422 , the finger flange  1436 , and the plunger member  1438  are described in U.S. Utility patent application Ser. No. 15/801,259, which was previously incorporated by reference herein. The method  1300  of manufacturing/assembling a multiple chamber safe injection system depicted in  FIG.  13    may take place, fully or in part, in a vacuum (e.g., vacuum chamber or vacuum room). The injection system/syringe body  1410 , the proximal and distal stopper members  1414 ,  1434 , the needle hub assembly  1422 , the finger flange  1436 , and the plunger member  1438  may be pre-sterilized before assembly. 
     While a single multiple chamber safe injection system is manufactured/assembled in the method  1300  depicted in  FIGS.  13  and  14 A to  14 J , the same method  1300  may be used to manufacture/assemble a plurality of multiple chamber safe injection systems either in parallel or in series. While the method  1300  depicted in  FIGS.  13  and  14 A to  14 J  involves a dual chamber system with two stopper members  1414 ,  1434 , in some embodiments, a third stopper member may be added to the multiple chamber safe injection system to define a third chamber using steps similar to those in  1322  and  1324  described above. In some embodiments, more than three stopper members and chambers may be formed in a multiple chamber safe injection system. 
     Injection System/Syringe Fill Distal Chamber from Back 
       FIG.  17    depicts a rack  1210  containing a plurality of injection system/syringe bodies  1410  coupled to a plurality of needle hub assemblies  1422  and stored in a container  1212 . The rack  1210  and the container  1212  are made from materials that are sterilizable. The container  1212  is closable with a seal  1214  (see  FIG.  12 B ) to maintain the sterility of the rack  1210  and injection system/syringe bodies  1410  and needle hub assemblies  1422  contained therein. The rack  1210  is removed from the container  1212  and one injection system/syringe body  1410  coupled to a needle hub assembly  1422  is removed from the rack  1210 . The rack  1210  has a plurality of features (e.g., sleeves and/or flanges)  1216  to hold the injection system/syringe bodies  1410  and needle hub assemblies  1422  with the distal end of the injection system/syringe body  1410  is pointed in a generally downward direction (see  FIG.  19 A ). 
       FIG.  18    depicts a method  1800  for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. Corresponding partially assembled components are depicted in  FIGS.  19 A to  19 H . The injection system/syringe body  1410 , the proximal and distal stopper members  1414 ,  1434 , the needle hub assembly  1422 , the finger flange  1436 , and the plunger member  1438  may be the same system components depicted in  FIGS.  14 A to  16 A  and described above. 
     At  1810 , a needle hub assembly  1422  is coupled to the distal end of the injection system/syringe body  1410  as shown in  FIG.  19 A . The needle hub assembly  1422  includes a needle  1424  having a needle proximal end  1426 . The needle hub assembly  1422  is coupled to the distal end of the injection system/syringe body  1410  by a user (e.g., using a tool) or by a mechanical device (e.g., robot). In some alternative embodiments, the injection system/syringe body  1410  may be supplied with the needle hub assembly  1422  coupled thereto. In some embodiments, the coupled the injection system/syringe body  1410  and needle hub assembly  1422  may be pre-sterilized. In other embodiments, pre-sterilized components may be supplied and assembled at the time of filling. 
     At  1812 , the injection system/syringe body  1410  coupled to the needle hub assembly  1422  is disposed in a rack with the injection system/syringe body  1410  pointed downward as shown in  FIGS.  17  and  19 A . The injection system/syringe body  1410  may be disposed in the rack by a user (e.g., using a tool) or by a mechanical device (e.g., robot). Alternatively, the injection system/syringe body  1410  may be closed with a luer cap as disclosed in  FIGS.  33 - 40    and described below. In this case the dual chamber system would be provided without a pre-attached needle. The transfer tube component may be pre-inserted into the syringe body or installed at the time of placing the luer cap. The user may attach a needle at the time of use by using a luer slip or luer lock connection method. 
     At  1814 , a first substance  1420  is introduced into the distal chamber  1418  through the open proximal end of the injection system/syringe body  1410  as shown in  FIG.  19 B . The first substance  1420  may be introduced directly through the opening at the proximal end of the injection system/syringe body  1410 . The first substance  1420  may be a liquid, solid (e.g., compressed powder), and/or a powder. In some embodiments where the first substance  1420  is a liquid, the first substance  1420  may be lyophilized in an optional step to form a powder as shown in  FIG.  19 C . 
     At  1816 , a distal stopper member  1414  is disposed in an interior  1412  of the injection system/syringe body  1410  as shown in  FIGS.  19 D and  19 E . The distal stopper member  1414  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The distal stopper member  1414  and the injection system/syringe body  1410  define proximal and distal chambers  1416 ,  1418  in the body interior  1412 . The distal stopper member  1414  may be positioned over an open proximal end of the injection system/syringe body  1410  to facilitate insertion of the distal stopper member  1414  into the body interior  1412  as shown in  FIG.  19 D . 
     The needle proximal end  1426  interferes with the distal stopper member  1414  to temporarily prevent distal movement of the distal stopper member  1414  relative to the injection system/syringe body  1410 . Components of the distal stopper member  1414  that interfere with the needle proximal end  1426  are depicted in  FIGS.  15 A to  15 D and  16  to  16 A , and described above. 
     At  1818 , a second substance  1432  is introduced into the proximal chamber  1416  through the open proximal end of the injection system/syringe body  1410  as shown in  FIG.  19 F . The second substance  1432  may be introduced directly through the opening at the proximal end of the injection system/syringe body  1410 . The second substance  1432  may be a liquid or another fluid. 
     At  1820 , a proximal stopper member  1434  is disposed in the interior  1412  of the injection system/syringe body  1410  as shown in  FIG.  19 G . The proximal stopper member  1434  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The proximal stopper member  1434  closes the proximal chambers  1416  defined by the injection system/syringe body  1410  and the distal stopper member  1414 . The proximal stopper member  1434  may be positioned over an open proximal end of the injection system/syringe body  1410  to facilitate insertion of the proximal stopper member  1434  into the body interior  1412 . The proximal stopper member  1438  may be inserted using a pressure differential or a small tube as described above. 
     In an optional step shown in  FIG.  19 H , a finger flange  1436  and a plunger member  1438  are coupled to the injection system/syringe body  1410 . The finger flange  1436  may be coupled to the injection system/syringe body  1410  such that it is prevented from moving along a longitudinal axis of the body  1410  (e.g., by snapping over a glass flange at the proximal end of the body  1410 ). The plunger member  1438  may be coupled to the injection system/syringe body  1410  such that it is movable along a longitudinal axis of the body  1410 . A distal end of the plunger member  1438  is also coupled to the proximal stopper member  1434  (e.g., using a threaded screw), such that movement of the plunger member  1438  relative to the injection system/syringe body  1410  moves the proximal stopper member  1434 . The finger flange  1436  and a plunger member  1438  may be coupled to the injection system/syringe body  1410  by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     While a single multiple chamber safe injection system is manufactured/assembled in the method  1800  depicted in  FIGS.  18  and  19 A to  19 H , the same method  1800  may be used to manufacture/assemble a plurality of multiple chamber safe injection systems either in parallel or in series. While the method  1800  depicted in  FIGS.  18  and  19 A to  19 H  involves a dual chamber system with two stopper members  1414 ,  1434 , in some embodiments, a third stopper member may be added to the multiple chamber safe injection system to define a third chamber using steps similar to those in  1818  and  1820  described above. In some embodiments, more than three stopper members and chambers may be formed in a multiple chamber safe injection system. 
     Cartridge Fill Distal Chamber from Front 
       FIGS.  20 A and  20 B  depict a rack  1210 ′ containing a plurality of cartridges  1410 ′ and stored in a container  1212 . The rack  1210 ′ and the container  1212  are made from materials that are sterilizable. The container  1212  is closable with a seal  1214  ( FIG.  20 A ) to maintain the sterility of the rack  1210 ′ and cartridges  1410 ′ contained therein. 
       FIG.  20 C  depicts the rack  1210 ′ removed from the container  1212  and one cartridge  1410 ′ removed from the rack  1210 ′. The rack  1210 ′ has a plurality of features (e.g., sleeves and/or flanges)  1216 ′ to hold the cartridges  1410 ′ in a first configuration in which the distal end of the cartridge  1410 ′ is pointed in a generally downward direction (see  FIG.  22 A ). In some embodiments, the features  1216 ′ are also configured to hold the cartridges  1410 ′ in a second configuration in which the proximal end of the cartridge  1410 ′ is pointed in a generally downward direction (see  FIG.  22 C ). 
       FIG.  21    depicts a method  2100  for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. Corresponding partially assembled components are depicted in  FIGS.  22 A to  22 J . 
     At  2110 , a cartridge  1410 ′ is disposed in a rack in a first (downward) configuration as shown in  FIG.  22 A . The cartridge  1410 ′ may be disposed in the rack by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  2112 , a distal stopper member  1414  is disposed in an interior  1412  of the cartridge  1410 ′ as shown in  FIG.  22 B . The distal stopper member  1414  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The distal stopper member  1414  and the cartridge  1410 ′ define proximal and distal chambers  1416 ,  1418  in the body interior  1412 . The distal stopper member  1414  may be positioned over an open proximal end of the cartridge  1410 ′ to facilitate insertion of the distal stopper member  1414  into the body interior  1412 . 
     At  2114 , the cartridge  1410 ′ is turned to a second (upward) configuration as shown in  FIG.  22 C . The cartridge  1410 ′ may be repositioned in the rack after being turned to the second configuration. Cartridge  1410 ′ may be turned and/or repositioned by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  2116 , a first substance  1420  is introduced into the distal chamber  1418  through the open distal end of the cartridge  1410 ′ as shown in  FIG.  22 C . The first substance  1420  may be introduced directly through the opening at the distal end of the cartridge  1410 ′. In some embodiments, a tube may be inserted through the opening at the distal end of the cartridge  1410 ′, and the first substance  1420  may be introduced through the tube. The first substance  1420  may be a liquid, a solid (e.g., compressed powder), and/or a powder. In some embodiments where the first substance  1420  is a liquid, the first substance  1420  may be lyophilized in an optional step to form a powder as shown in  FIG.  22 D . 
     At  2118 , a cartridge cap  1440  and a needle hub assembly  1422 ′ are coupled to the distal end of the cartridge  1410 ′ as shown in  FIG.  22 E . First, the cartridge cap  1440  may be coupled to the distal end of the cartridge  1410 ′ by a user (e.g., using a tool) or by a mechanical device (e.g., robot). Exemplary cartridge caps  1440  are shown in  FIGS.  23 A and  23 B . The cartridge caps  1440  include a crimp seal  1442  with an opening therein and a septum  1444 . The crimp seal  1442  may be made from aluminum and the septum  1444  may be made from rubber. The cartridge cap  1440  may be coupled to the distal end of the cartridge  1410 ′ by crimping the crimp seal  1442  around and enlarge portion of the cartridge  1410 ′ at a distal end thereof. 
     Next, the needle hub assembly  1422 ′ is coupled to the distal end of the cartridge  1410 ′ on top of the cartridge cap  1440  as shown in  FIG.  22 G . As shown in  FIG.  22 F , the needle hub assembly  1422 ′ includes a needle  1424  having a needle proximal end  1426 . The needle proximal end  1426  interferes with the distal stopper member  1414  to temporarily prevent distal movement of the distal stopper member  1414  relative to the cartridge  1410 ′. The needle hub assembly  1422 ′ is coupled to the distal end of the cartridge  1410 ′ by a user (e.g., using a tool) or by a mechanical device (e.g., robot). Components of the distal stopper member  1414  that interfere with the needle proximal end  1426  are depicted in  FIGS.  15 A to  15 D and  16  to  16 A , and described above. 
     In some alternative embodiments, the cartridge  1410 ′ may be supplied with a needle hub assembly  1422 ′ or luer cap coupled thereto. In some embodiments, the coupled the cartridge  1410 ′, needle hub assembly  1422 ′, and/or luer cap may be pre-sterilized. In other embodiments, pre-sterilized components may be supplied and assembled at the time of filling. 
     While a cartridge cap  1440  is included in the embodiment depicted in  FIG.  22 E , the cartridge cap  1440  is optional and the needle hub assembly  1422 ′ is directly coupled to the distal end of the cartridge  1410 ′ in some embodiments (compare  FIGS.  24 A  (no cap) and  24 B (with cap)). 
     At  2120 , the cartridge  1410 ′ is turned back to the first (downward) configuration as shown in  FIG.  22 G . The cartridge  1410 ′ may be repositioned in the rack after being turned back to the first configuration. Cartridge  1410 ′ may be turned and/or repositioned by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  2122 , a second substance  1432  is introduced into the proximal chamber  1416  through the open proximal end of the cartridge  1410 ′ as shown in  FIG.  22 H . The second substance  1432  may be introduced directly through the opening at the proximal end of the cartridge  1410 ′. The second substance  1432  may be a liquid or another fluid. 
     At  2124 , a proximal stopper member  1434  is disposed in the interior  1412  of the cartridge  1410 ′ as shown in  FIG.  22 I . The proximal stopper member  1434  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The proximal stopper member  1434  closes the proximal chambers  1416  defined by the cartridge  1410 ′ and the distal stopper member  1414 . The proximal stopper member  1434  may be positioned over an open proximal end of the cartridge  1410 ′ to facilitate insertion of the proximal stopper member  1434  into the body interior  1412 . The proximal stopper member  1438  may be inserted using a pressure differential or a small tube as described above. 
     In an optional step shown in  FIG.  22 J , a finger flange  1436  and a plunger member  1438  are coupled to the cartridge  1410 ′. The finger flange  1436  may be coupled to the cartridge  1410 ′ such that it is prevented from moving along a longitudinal axis of the body  1410  (e.g., using an adhesive). The plunger member  1438  may be coupled to the cartridge  1410 ′ such that it is movable along a longitudinal axis of the body  1410 . A distal end of the plunger member  1438  is also coupled to the proximal stopper member  1434  (e.g., using a threaded screw), such that movement of the plunger member  1438  relative to the cartridge  1410 ′ moves the proximal stopper member  1434 . The finger flange  1436  and a plunger member  1438  may be coupled to the cartridge  1410 ′ by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     Further details regarding the cartridge  1410 ′, the proximal and distal stopper members  1414 ,  1434 , the needle hub assembly  1422 ′, the finger flange  1436 , and the plunger member  1438  are described in U.S. Utility patent application Ser. No. 15/801,259, which was previously incorporated by reference herein. The method  2100  of manufacturing/assembling a multiple chamber safe injection system depicted in  FIG.  21    may take place, fully or partially, in a vacuum (e.g., vacuum chamber or vacuum room). The cartridge  1410 ′, the proximal and distal stopper members  1414 ,  1434 , the needle hub assembly  1422 ′, the finger flange  1436 , and the plunger member  1438  may be pre-sterilized before assembly. 
     While a single multiple chamber safe injection system is manufactured/assembled in the method  2100  depicted in  FIGS.  21  and  22 A  to  22 J, the same method  2100  may be used to manufacture/assemble a plurality of multiple chamber safe injection systems either in parallel or in series. While the method  2100  depicted in  FIGS.  21  and  22 A to  22 J  involves a dual chamber system with two stopper members  1414 ,  1434 , in some embodiments, a third stopper member may be added to the multiple chamber safe injection system to define a third chamber using steps similar to those in  2122  and  2124  described above. In some embodiments, more than three stopper members and chambers may be formed in a multiple chamber safe injection system. 
     Cartridge Fill Distal Chamber from Back, Pierce Then Fill 
       FIG.  25    depicts a rack  1210 ′ containing a plurality of cartridges  1410 ′ and coupled to a plurality of needle hub assemblies  1422 ′ and stored in a container  1212 . The rack  1210 ′ and the container  1212  are made from materials that are sterilizable. The container  1212  is closable with a seal  1214  (see  FIG.  12 B ) to maintain the sterility of the rack  1210 ′ and cartridges  1410 ′ and needle hub assemblies  1422 ′ contained therein. The rack  1210 ′ is removed from the container  1212  and one cartridge  1410 ′ coupled to a needle hub assembly  1422 ′ is removed from the rack  1210 ′. The rack  1210 ′ has a plurality of features (e.g., sleeves and/or flanges)  1216 ′ to hold the cartridges  1410 ′ and needle hub assemblies  1422 ′ with the distal end of the cartridge  1410 ′ is pointed in a generally downward direction (see  FIG.  27 A ). 
       FIG.  26    depicts a method  2600  for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. Corresponding partially assembled components are depicted in  FIGS.  27 A  to  27 G. The cartridge  1410 ′, the proximal and distal stopper members  1414 ,  1434 , the needle hub assembly  1422 ′, cartridge cap  1440 , the finger flange  1436 , and the plunger member  1438  may be the same system components depicted in  FIGS.  22 A to  24 B  and described above. 
     At  2610 , a cartridge cap  1440  and a needle hub assembly  1422 ′ are coupled to the distal end of the cartridge  1410 ′ as shown in  FIG.  27 A . First, the cartridge cap  1440  may be coupled to the distal end of the cartridge  1410 ′ by a user (e.g., using a tool) or by a mechanical device (e.g., robot). Exemplary cartridge caps  1440  are shown in  FIGS.  23 A and  23 B , and described above. The cartridge cap  1440  may be coupled to the distal end of the cartridge  1410 ′ by crimping the crimp seal  1442  around and enlarged portion of the cartridge  1410 ′ at a distal end thereof. This step may be performed at the time of filling or may be performed previous to filling and provided pre-sterilized to the filling machine. 
     Next, the needle hub assembly  1422 ′ is coupled to the distal end of the cartridge  1410 ′ on top of the cartridge cap  1440  as shown in  FIG.  27 A . As shown in  FIG.  22 F , the needle hub assembly  1422 ′ includes a needle  1424  having a needle proximal end  1426 . While a cartridge cap  1440  is included in the embodiment depicted in  FIG.  27 A , the cartridge cap  1440  is optional and the needle hub assembly  1422 ′ is directly coupled to the distal end of the cartridge  1410 ′ in some embodiments (compare  FIGS.  24 A  (no cap) and  24 B (with cap)). The coupling of the needle hub assembly  1422 ′ to the cartridge  1410 ′ may be performed at the time of filling or the coupling may be performed previous to filling and a pre-sterilized coupled system is provided to the filling machine. 
     At  2612 , the cartridge  1410 ′ coupled to the needle hub assembly  1422 ′ is disposed in a rack with the cartridge  1410 ′ pointed downward as shown in  FIGS.  25  and  27 A . The cartridge  1410 ′ may be disposed in the rack by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  2614 , a first substance  1420  is introduced into the distal chamber  1418  through the open proximal end of the cartridge  1410 ′ as shown in  FIG.  27 B . The first substance  1420  may be introduced directly through the opening at the proximal end of the cartridge  1410 ′. The first substance  1420  may be a liquid, a solid (e.g., compressed powder), and/or a powder. In some embodiments where the first substance  1420  is a liquid, the first substance  1420  may be lyophilized in an optional step to form a powder as shown in  FIG.  27 C . 
     At  2616 , a distal stopper member  1414  is disposed in an interior  1412  of the cartridge  1410 ′ as shown in  FIGS.  27 C and  27 D . The distal stopper member  1414  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The distal stopper member  1414  and the cartridge  1410 ′ define proximal and distal chambers  1416 ,  1418  in the body interior  1412 . The distal stopper member  1414  may be positioned over an open proximal end of the cartridge  1410 ′ to facilitate insertion of the distal stopper member  1414  into the body interior  1412  as shown in  FIG.  27 C . 
     The needle proximal end  1426  interferes with the distal stopper member  1414  to temporarily prevent distal movement of the distal stopper member  1414  relative to the cartridge  1410 ′. Components of the distal stopper member  1414  that interfere with the needle proximal end  1426  are depicted in  FIGS.  15 A to  15 D and  16  to  16 A , and described above. 
     At  2618 , a second substance  1432  is introduced into the proximal chamber  1416  through the open proximal end of the cartridge  1410 ′ as shown in  FIG.  27 E . The second substance  1432  may be introduced directly through the opening at the proximal end of the cartridge  1410 ′. The second substance  1432  may be a liquid or another fluid. 
     At  2620 , a proximal stopper member  1434  is disposed in the interior  1412  of the cartridge  1410 ′ as shown in  FIG.  27 F . The proximal stopper member  1434  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The proximal stopper member  1434  closes the proximal chambers  1416  defined by the cartridge  1410 ′ and the distal stopper member  1414 . The proximal stopper member  1434  may be positioned over an open proximal end of the cartridge  1410 ′ to facilitate insertion of the proximal stopper member  1434  into the body interior  1412 . The proximal stopper member  1438  may be inserted using a pressure differential or a small tube as described above. 
     In an optional step shown in  FIG.  27 G , a finger flange  1436  and a plunger member  1438  are coupled to the cartridge  1410 ′. The finger flange  1436  may be coupled to the cartridge  1410 ′ such that it is prevented from moving along a longitudinal axis of the body  1410  (e.g., by snapping over a glass flange at the proximal end of the body  1410 ). The plunger member  1438  may be coupled to the cartridge  1410 ′ such that it is movable along a longitudinal axis of the body  1410 . A distal end of the plunger member  1438  is also coupled to the proximal stopper member  1434  (e.g., using a threaded screw), such that movement of the plunger member  1438  relative to the cartridge  1410 ′ moves the proximal stopper member  1434 . The finger flange  1436  and a plunger member  1438  may be coupled to the cartridge  1410 ′ by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     While a single multiple chamber safe injection system is manufactured/assembled in the method  2600  depicted in  FIGS.  26  and  27 A to  27 G , the same method  2600  may be used to manufacture/assemble a plurality of multiple chamber safe injection systems either in parallel or in series. While the method  2600  depicted in  FIGS.  26  and  27 A to  27 G  involves a dual chamber system with two stopper members  1414 ,  1434 , in some embodiments, a third stopper member may be added to the multiple chamber safe injection system to define a third chamber using steps similar to those in  2618  and  2620  described above. In some embodiments, more than three stopper members and chambers may be formed in a multiple chamber safe injection system. 
     Cartridge Fill Distal Chamber from Back, Fill Then Pierce 
       FIG.  28    depicts a method  2800  for manufacturing/assembling a multiple chamber safe injection system according to some embodiments. Corresponding partially assembled components are depicted in  FIGS.  29 A to  29 G . The cartridge  1410 ′, the proximal and distal stopper members  1414 ,  1434 , the needle hub assembly  1422 ′, cartridge cap  1440 , the finger flange  1436 , and the plunger member  1438  may be the same system components depicted in  FIGS.  22 A to  24 B  and described above. 
     At  2810 , a cartridge cap  1440  is coupled to the distal end of the cartridge  1410 ′ as shown in  FIG.  29 A . The cartridge cap  1440  may be coupled to the distal end of the cartridge  1410 ′ by a user (e.g., using a tool) or by a mechanical device (e.g., robot). Exemplary cartridge caps  1440  are shown in  FIGS.  23 A and  23 B , and described above. The cartridge cap  1440  may be coupled to the distal end of the cartridge  1410 ′ by crimping the crimp seal  1442  around and enlarge portion of the cartridge  1410 ′ at a distal end thereof. In some alternative embodiments, the cartridge  1410 ′ may be supplied with the cartridge cap  1440  coupled and both components pre-sterilized. 
     At  2812 , the cartridge  1410 ′ coupled to the cartridge cap  1440  is disposed in a rack with the cartridge  1410 ′ pointed downward as shown in  FIGS.  20 C and  29 A . The cartridge  1410 ′ may be disposed in the rack by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     At  2814 , a first substance  1420  is introduced into the distal chamber  1418  through the open proximal end of the cartridge  1410 ′ as shown in  FIG.  29 B . The first substance  1420  may be introduced directly through the opening at the proximal end of the cartridge  1410 ′. The first substance  1420  may be a liquid, solid (e.g., compressed powder), and/or a powder. In some embodiments where the first substance  1420  is a liquid, the first substance  1420  may be lyophilized in an optional step to form a powder as shown in  FIG.  29 C . 
     At  2816 , a needle hub assembly  1422 ′ is coupled to the distal end of the cartridge  1410 ′ on top of the cartridge cap  1440  as shown in  FIG.  29 E . As shown in  FIG.  22 F , the needle hub assembly  1422 ′ includes a needle  1424  having a needle proximal end  1426 . During insertion of the needle hub assembly  1422 ′into the cartridge interior  1412 , the needle  1424  and a needle proximal end  1426  pierce the cartridge cap  1440 . The septum  1444  in the cartridge cap  1440  depicted in  FIGS.  23 A and  23 B  is configured to be pierced by the needle proximal end  1426 . In some alternative embodiments, the cartridge  1410 ′ may be supplied with the needle hub assembly  1422 ′ coupled and both components pre-sterilized. 
     At  2818 , a distal stopper member  1414  is disposed in an interior  1412  of the cartridge  1410 ′ as shown in  FIGS.  29 E and  29 F . The distal stopper member  1414  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The distal stopper member  1414  and the cartridge  1410 ′ define proximal and distal chambers  1416 ,  1418  in the body interior  1412 . The distal stopper member  1414  may be positioned over an open proximal end of the cartridge  1410 ′ to facilitate insertion of the distal stopper member  1414  into the body interior  1412 . The distal stopper member  1414  may be inserted using a pressure differential or a small tube as described above. 
     The needle proximal end  1426  interferes with the distal stopper member  1414  to temporarily prevent distal movement of the distal stopper member  1414  relative to the cartridge  1410 ′. Components of the distal stopper member  1414  that interfere with the needle proximal end  1426  are depicted in  FIGS.  15 A to  15 D and  16  to  16 A , and described above. 
     At  2820 , a second substance  1432  is introduced into the proximal chamber  1416  through the open proximal end of the cartridge  1410 ′ as shown in  FIG.  29 G . The second substance  1432  may be introduced directly through the opening at the proximal end of the cartridge  1410 ′. The second substance  1432  may be a liquid or another fluid. 
     At  2822 , a proximal stopper member  1434  is disposed in the interior  1412  of the cartridge  1410 ′ as shown in  FIG.  29 H . The proximal stopper member  1434  may be inserted by a user (e.g., using a tool) or by a mechanical device (e.g., robot). The proximal stopper member  1434  closes the proximal chambers  1416  defined by the cartridge  1410 ′ and the distal stopper member  1414 . The proximal stopper member  1434  may be positioned over an open proximal end of the cartridge  1410 ′ to facilitate insertion of the proximal stopper member  1434  into the body interior  1412 . The proximal stopper member  1438  may be inserted using a pressure differential or a small tube as described above. 
     In an optional step (not shown), a finger flange and a plunger member are coupled to the cartridge  1410 ′. The finger flange may be coupled to the cartridge  1410 ′ such that it is prevented from moving along a longitudinal axis of the body  1410  (e.g., by snapping over a glass flange at the proximal end of the body  1410 ). The plunger member may be coupled to the cartridge  1410 ′ such that it is movable along a longitudinal axis of the body  1410 . A distal end of the plunger member is also coupled to the proximal stopper member  1434  (e.g., using a threaded screw), such that movement of the plunger member relative to the cartridge  1410 ′ moves the proximal stopper member  1434 . The finger flange and a plunger member may be coupled to the cartridge  1410 ′ by a user (e.g., using a tool) or by a mechanical device (e.g., robot). 
     While a single multiple chamber safe injection system is manufactured/assembled in the method  2800  depicted in  FIGS.  28  and  29 A to  29 G , the same method  2800  may be used to manufacture/assemble a plurality of multiple chamber safe injection systems either in parallel or in series. While the method  2800  depicted in  FIGS.  28  and  29 A to  29 G  involves a dual chamber system with two stopper members  1414 ,  1434 , in some embodiments, a third stopper member may be added to the multiple chamber safe injection system to define a third chamber using steps similar to those in  2818  and  2820  described above. In some embodiments, more than three stopper members and chambers may be formed in a multiple chamber safe injection system. 
       FIG.  30    depicts a cartridge stopper  1446  according to some embodiments. The cartridge stopper  1446  can be made from a soft polymer such that it is pierceable by the needle proximal end  1426 . Further, the cartridge stopper  1446  includes a vent  1448  for lyophilization of liquids in the cartridge interior  1412 . 
     Autoinjector System 
     Single Chamber 
       FIGS.  31 A to  31 H  depict an auto injector system  3100  including a disposable injection system/syringe  3110  and a reusable drive system  3150  according to some embodiments. The autoinjector system  3100  allows use of injection system/syringes  3110  that are readily available in a clinical setting without having to add items to a supply chain. The autoinjector system  3100  also includes a safety function to minimize exposure of a sharp needle as described below. These and other advantages of the autoinjector system  3100  are explained below. 
     As shown in  FIG.  31 A , the disposable injection system/syringe  3110  includes an injection system/syringe body  3112 , a stopper member  3114 , a plunger member  3116 , a finger flange  3118 , a needle hub assembly  3120 , a rigid needle shield  3122 , and a pull ring  3124  to facilitate removal of the rigid needle shield  3122  from the needle hub assembly  3120 . The injection system/syringe  3110  may be a safe injection system that retracts the sharp needle at least into the injection system/syringe body  3112  to minimize the risk of a needle stick. Examples of such safe injection systems are described in U.S. Utility patent application Ser. No. 14/696,342, which was previously incorporated by reference herein. The reusable drive system  3150  includes a drive system body  3152 , a plunger actuator/pusher  3154 , a flange holder/carriage  3156 , and a collar  3164 . 
     When the injection system/syringe  3110  is mounted in the drive system  3150 , as shown in  FIG.  31 B , the plunger actuator/pusher  3154  is configured to move the plunger member  3116  distally relative to the injection system/syringe body  3112 . The flange holder/carriage  3156  is configured to move the injection system  3110  distally and/or proximally relative to the drive system body  3152 . The plunger actuator/pusher  3154  and the flange holder/carriage  3156  are in their respective full proximal positions in  FIGS.  31 A and  31 B . In this position, the collar  3164  of the drive system  3150  prevents the sharp needle of the injection system/syringe  3110  from contacting a user&#39;s skin. In addition, in  FIG.  31 B , the rigid needle shield  3122  prevents the needle from contacting a user&#39;s skin. 
       FIG.  31 C  shows the autoinjector system  3100  in a closed configuration (versus the open configuration in  FIGS.  31 A and  31    B). In the close configuration, various user interface components of the drive system  3150  are visible. The drive system  3150  includes a display  3158 , a button  3160 , and the light ring  3162  around the button  3160 . In the system configuration depicted in  FIG.  31 C , the display  3158  renders an indication of the size of the injection systems/syringe (e.g., 1.0 ml). The button  3160  allows a user to provide input to the autoinjector system  3100 . The light ring  3162  can change colors to indicate various steps in the injection process. As shown in  FIG.  31 C , the pull ring  3124  is accessible at the distal end of the drive system  3150  because it extends distally beyond the collar  3164 . 
     The top half of the drive system  3150  has been cut away from  FIGS.  31 D to  31 G  to visualize various components of the autoinjector system  3100  during injection with the drive system  3150  in a closed configuration. 
     In  FIGS.  31 D , the rigid needle shield  3122  has been removed from the needle hub assembly  3120 . In some embodiments, the autoinjector system  3100  renders an instruction on the display  3158  for the user to pull on the pull ring  3124  to remove the rigid needle shield  3122  from the needle hub assembly  3120 . In some embodiments, the autoinjector  3100  includes components that grasp the rigid needle shield  3122  (e.g., one or more arms) while the flange holder/carriage  3156  moves the injection system/syringe  3110  (e.g., from a distal position to a proximal position) to separate the rigid needle shield  3122  from the needle hub assembly  3120 . In such embodiments, the user would only have to remove the separated rigid needle shield  3122  from the auto injection system  3100 . The collar  3164  prevents exposure of the needle  3126  to a user. 
     In  FIG.  31 E , the flange holder/carriage  3156  has moved the injection system/syringe  3110  distally. At the same time, the plunger actuator/pusher  3154  has moved the same distance distally to maintain contact with the thumb pad at the proximal end of the plunger member  3116 . Moving the injection system/syringe  3110  distally extends the needle  3126  distally beyond the collar  3164 , thereby exposing the needle  3126  for injection. Before the flange holder/carriage  3156  moves the injection system/syringe  3110  distally, the autoinjector system  3100  may render an instruction on the display  3158  for the user to press the autoinjector against an injection site. In such embodiments, moving the injection system/syringe  3110  distally may puncture the injection site. 
     In  FIG.  31 F , the plunger actuator/pusher  3154  has moved to its full distal position. This movement drives the plunger member  3116  and the stopper member  3114  attached thereto distally to eject a medicine from the injection systems/syringe  3110  through the needle  3126  and into the patient. 
     In  FIG.  31 G , movement of the plunger member  3116  and the stopper member  3114  two and end of injection position has caused the needle  3126  to be retracted into the injection systems/syringe body  3112  as described U.S. Utility patent application Ser. No. 14/696,342, which was previously Incorporated by reference herein. Retraction of the needle  3126  renders the injection systems/syringe  3110  safe for removal from the drive system  3150  as shown in  FIG.  31 H . After the used injection system/syringe  3110  has been removed, a new injection system/syringe  3110  can be loaded into the drive system  3150  to ready the auto injector system  3100  ready for another injection. 
     The drive system  3150  also includes a first motor to move the plunger actuator/pusher  3154 , a second motor to move the flange holder/carriage  3156 , a controller operatively coupled to the first and second motors, and one or more sensors operatively coupled to the controller. The sensors may include one or more of an accelerometer, a contact sensor, a position sensor, a gyroscope, a thermometer, and a skin contact sensor. In some embodiments, the sensor is a skin contact sensor, and the controller injects the medicine only when the skin contact sensor confirms contact between the autoinjector system  3100  and a patient. 
     Dual Chamber 
       FIGS.  32 A to  32 J  depict an autoinjector system  3200  configured for use with a multiple chamber injection system  3210 . The drive system  3250  depicted in  FIGS.  32 A to  32 J  is similar to the drive system  3150  depicted in  FIGS.  31 A to  31 H . In fact, drive systems  3150 ,  3250  may be the same drive system with altered programming. 
     As shown in  FIG.  32 A , the disposable injection system/syringe  3210  includes an injection system/syringe body  3212 , first and second stopper members  3228 ,  3214 , a plunger member  3216 , a finger flange  3218 , a needle hub assembly  3220 , and a rigid needle shield  3222 . The injection system/syringe  3210  may be a safe injection system that retracts the sharp needle at least into the injection system/syringe body  3212  to minimize the risk of a needle stick. Examples of such safe injection systems are described in U.S. Utility patent application Ser. No. 15/801,259, which was previously incorporated by reference herein. The reusable drive system  3250  includes a drive system body  3252 , a plunger actuator/pusher  3254 , a flange holder/carriage  3256 , and a collar  3264 . 
     When the injection system/syringe  3210  is mounted in the drive system  3250 , as shown in  FIG.  32 B , the plunger actuator/pusher  3254  is configured to move the plunger member  3216  distally relative to the injection system/syringe body  3212 . The flange holder/carriage  3256  is configured to move the injection system  3210  distally and/or proximally relative to the drive system body  3252 . The plunger actuator/pusher  3254  and the flange holder/carriage  3256  are in their respective full proximal positions in  FIGS.  32 A and  32 B . In this position, the collar  3264  of the drive system  3250  prevents the sharp needle of the injection system/syringe  3210  from contacting a user&#39;s skin. In addition, in  FIG.  32 B , the rigid needle shield  3222  prevents the needle from contacting a user&#39;s skin. 
       FIG.  32 C  shows the autoinjector system  3200  in a closed configuration (versus the open configuration in  FIGS.  32 A and  32 B ). In the close configuration, various user interface components of the drive system  3250  are visible. The drive system  3250  includes a display  3258 , a button  3260 , and the light ring  3262  around the button  3260 . In the system configuration depicted in  FIG.  32 C , the display  3258  renders an indication of the size of the injection systems/syringe (e.g., 1.0 ml). The button  3260  allows a user to provide input to the autoinjector system  3200 . The light ring  3262  can change colors to indicate various steps in the injection process. As shown in  FIG.  32 C , the rigid needle shield  3222  is not easily accessible at the distal end of the drive system  3250  because it barely extends distally beyond the collar  3264 . 
       FIGS.  32 D to  32 J  depict various steps in a method of mixing and injecting medicines using the autoinjector system  3200  according to some embodiments. In  FIG.  32 D , the display  3258  is rendering a message instructing a user to push the button  3262  mix a medicine with a diluent. This message can be accompanied by the light ring  3262  turning green to signal go. When the user presses the button  3262 , the plunger actuator/pusher  3254  moves distally to transfer diluent from a proximal chamber to a distal chamber as shown in  FIG.  7 G to  7 J . In  FIG.  32 E , the display  3250  is rendering a message instructing a user to shake the autoinjector system  3202  mix the medicine with the diluent. 
     In  FIG.  32 F , the display  3250  is rendering a message instructing a user to point the autoinjector system  3200  upward and will move the rigid needle shield  3222 . As shown in  FIG.  32 G , when a position sensor in the autoinjector system  3200  detects that the system  3200  is pointed upward, the flange holder/carriage  3256  moves the injection systems/syringe  3210  distally to extend the rigid needle shield  3222  for removal. Removing the rigid needle shield  3222  only when the system  3200  is pointed upward prevents accidental expulsion of medicine due to pressure buildup from fluid transfer and mixing. 
     In some embodiments, the user is expected to pull on the rigid needle shield  3222  to remove it from the needle hub assembly  3220 . In some embodiments, the autoinjector  3200  includes components that grasp the rigid needle shield  3222  (e.g., one or more arms) while the flange holder/carriage  3256  moves the injection system/syringe  3210  (e.g., from a distal position to a proximal position) to separate the rigid needle shield  3222  from the needle hub assembly  3220 . In such embodiments, the user would only have to remove the separated rigid needle shield  3222  from the auto injection system  3200 . The collar  3264  prevents exposure of the needle  3226  to a user as shown in  FIG.  32 H . 
     In  FIG.  32 F , the display  3250  is rendering a message instructing a user to place the autoinjector system  3200  on user&#39;s thigh and to press the button  3260  to give the injection. In some embodiments, a skin contact sensor prevents injection until contact between the autoinjector system  3200  and the user is detected. Detection of contact and readiness for injection can be indicated using the light ring  3262  (e.g., a green ring for go). When the user presses the button  3260  for injection, the flange holder/carriage  3256  moves the injection systems/syringe  3210  distally to insert the needle into the patient, and the plunger actuator/pusher  3254  moves distally to complete the injection as shown in  FIGS.  7 K to  7 P . 
     After the injection is completed, the display  3250  renders a message confirming the injection and instructing a user to remove and dispose of the spent syringe. A new injection system/syringe  3210  can be loaded into the drive system  3252  prepare the autoinjector system  3200  for another injection. 
     Multiple Chamber Safe Injection System with Luer Connector 
       FIGS.  33  to  40    depict a multiple chamber safe injection system  3300  with a luer connector  3310 . As shown in  FIGS.  33  and  34   , the luer connector  3310  is a standard connector that facilitates use of the system  3300  with a wide variety of needles and tubing. The system  3300  includes a standard luer cap  3312  that seals the luer connector  3310  during mixing of the drug components before delivery/injection. 
     In some embodiments, the drug components include a drug solvent  3314  in a proximal chamber and a drug powder and/or solid (e.g., compressed powder)  3316  and a distal chamber. The drug solvent  3314  can be transferred from the proximal chamber to the distal chamber to mix with the drug powder and/or solid  3316  via a transfer pipe  3318  with various openings. The distal end of the transfer pipe  3318  is coupleable via the Luer connector  3310  with a wide variety of needles and tubing. The finger flange and a plunger member also include a ratcheting/anti-retraction system  3320  to limit motion of the plunger member during mixing to the distal direction. 
       FIG.  35    depicts a transfer pipe  3318  for use with the multiple chamber safe injection system  3300  according to some embodiments. The proximal end of the transfer pipe  3318  includes a piercing tip  3322  configured to pierce the distal stopper member to allow the drug diluent  3314  to transfer from the proximal chamber to the distal chamber to mix with the drug powder and/or solid  3316 . The next feature distally along the transfer pipe  3318  is a liquid entrance slot  3324  configured to allow the drug diluent  3314  to enter from the proximal chamber. The next feature is a liquid exit opening  3326  configured to allow the drug diluent  3314  to exit to the distal chamber. The liquid entrance slot  3324  and the liquid exit opening  3326  are configured such that they span the distal stopper member to maximize liquid transfer. The next feature is a blocking rod  3328  to prevent the drug diluent  3314  from exiting out the distal end of the transfer pipe  3318 . The next feature is a washer  3330  configured to provide a reactive force to allow the piercing tip  3322  to pierce the distal stopper member. The next feature is an exit slot  3332  configured to allow the mixed drug to enter the distal end of the transfer pipe  3318 . The distal most feature is an expanded end opening  3334  configured to mate with a variety of needles and tubing via the luer connector  3310 . The expanded end opening also provides friction with the luer passage to hold the transfer pipe  3318  in place during filling of the system  3300 . 
       FIG.  36    depicts the fluid path  3336  during transfer of the drug diluent  3314  from the proximal chamber to the distal chamber. As described above, the fluid path  3336  goes through the liquid entrance slot  3324 , travels along a proximal portion of the transfer pipe  3318 , and exits the liquid exit opening  3326 . Transfer of the drug diluent  3314  from the proximal chamber to the distal chamber increases the pressure in the distal chamber. The ratcheting/anti-retraction system  3320  prevents unwanted proximal movement of the plunger member resulting from the built-up pressure in the distal chamber. The teeth  3338  of the ratcheting/anti-retraction system  3320  are only present at a distal portion of the plunger member, which interacts with tabs  3340  in the finger flange during mixing. Even if the user releases pressure on the plunger member during transfer, the ratcheting system/anti-retraction  3320  holds the plunger member in place. An alternative ratcheting/anti-retraction system is described below. 
       FIG.  37    depicts the fluid path  3336  at the end of the transfer of the drug diluent  3314  from the proximal chamber to the distal chamber. The liquid entrance slot  3324  allows the drug diluent to continue to transfer even as the proximal and distal stoppers approach each other. 
       FIG.  38    depicts the multiple chamber safe injection system  3300  after the transfer of the drug diluent  3314  is complete. Pressurized air in the distal chamber is prevented from pushing the plunger member proximally by the ratcheting system  3320 . The user can shake the system  3300  to mix the drug diluent  3314  with the drug powder and/or solid  3316  in the distal chamber. 
       FIG.  39    depicts the multiple chamber safe injection system  3300  after the luer cap  3312  has been removed with the system  3300  in an upward position to avoid the pressure in the distal chamber interjecting any of the mixed drug therein. Instead pressurized air is purged from the distal chamber. A needle  3342  with a corresponding luer connector is coupled to the luer connector  3310  in the system  3300  to prepare the system  3300  for injection. 
       FIG.  40    depicts the multiple chamber safe injection system  3300  during injection. The fluid path  3344  during injection is along the outside of the distal end of the transfer pipe  3318  and through the needle  3342 . During injection, the blocking rod  3328  prevents the mixed drug from traveling retrograde into the plunger member. The plunger member also includes an elastomeric seal to prevent backflow. Because the plunger member has moved relative to the finger flange such that the ratchet teeth at this gauge from the tabs, the plunger member can be moved in both a distal and a proximal direction during injection. 
     Vent Plug 
       FIGS.  41  to  47    depict a multiple chamber injection system  4100  with a vent plug  4154  according to some embodiments. The vent plug  4154  is configured (e.g., sized and shaped) to allow air to escape the system  4100  while substantially retaining liquids. As shown in  FIG.  41   , the system  4100  includes a syringe body  4110  having a needle coupling member  4156  at a distal end thereof. The needle coupling member  4156  may be a female Luer connector. The system  4100  also includes a finger flange  4136  coupled to a proximal end of the syringe body  4110  and a plunger member  4138  inserted through the finger flange  4136  and into an interior of the syringe body  4110 . 
     Also disposed in the interior of the syringe body  4110  are proximal and distal stopper members  4134 ,  4114 . The proximal and distal stopper members  4134 ,  4114  and the syringe body  4110  define a proximal chamber  4116 . The distal stopper member  4114  and the syringe body  4110  define a distal chamber  4118 . In the embodiment depicted in  FIG.  41   , the distal chamber  4118  contains a gas  4152  (e.g., air) and the proximal chamber  4116  contains a liquid  4132 . The system  4100  also includes a mix tube  4124  configured to pierce the distal stopper member  4114  to fluidly couple the proximal and distal chambers  4116 ,  4118 .  FIG.  41 A  depicts an anti-retraction mechanism  3321  (described below) for use with the multiple chamber injection system  4100  according to some embodiments. 
     The system  4100  further includes a cap  4150  (e.g., Luer cap) coupled to the needle coupling member  4156  for storage of the system  4100  components before use (e.g., injection). Moreover, the system  4100  includes a vent plug  4154  disposed at least partially in the needle coupling member  4156  and around a distal end of the mix tube  4124 . The vent plug  4154  is configured (sized and shaped) to allow air to escape the system  4100  while substantially retaining liquids. 
       FIG.  42    depicts the system  4100  depicted in  FIG.  41    after the plunger member  4138  and the proximal stopper member  4134  coupled thereto have been inserted distally into the interior of the syringe body  4110  according to some embodiments. Before the proximal end of the mix tube  4124  pierces completely through the distal stopper member  4114  (as shown in  FIG.  41   ), the incompressibility of the liquid  4132  in the proximal chamber  4116  transmits distally directed force from the plunger member  4138  and the proximal stopper member  4134  to the distal stopper member  4114  moving the distal stopper member  4114  distally. Distal movement of the distal stopper member  4114  causes the proximal end of the mix tube  4124  to pierce completely through the distal stopper member  4114  and fluidly couple the proximal and distal chambers  4116 ,  4118 . Fluidly coupling the proximal and distal chambers  4116 ,  4118  allows the liquid  4132  to be driven from the proximal chamber  4116  to the distal chamber  4118  by a distally directed force from the plunger member  4138  and the proximal stopper member  4134  as shown in  FIG.  42   . 
     Also shown in  FIG.  42   , the proximal chamber  4116  has collapsed almost completely, and almost all of the liquid  4132  has been driven from the proximal chamber  4116  to the distal chamber  4118 . The volume of the liquid  4132  driven into the distal chamber  4118  compresses the gas  4152  in the distal chamber  4118  increasing the pressure in the distal chamber  4118 . If this increased pressure is not vented from the distal chamber  4118 , it may unintentionally eject some of the liquid  4132  from the distal chamber  4118 , both wasting the liquid  4132  and reducing the accuracy and precision of the system  4100 . Before the cap  4150  is removed from the system  4100 , the increased pressure in the distal chamber  4118  may also be exerted back through the mix tube  4124 , thereby moving some of the liquid  4132  back into the proximal chamber  4116  and reducing the accuracy and precision of the system  4100 . The back pressure may also move the proximal stopper member  4134  and the plunger member  4138  proximally. Some multiple chamber injection systems include latches on the plunger member to prevent proximal movement of the plunger member. 
       FIGS.  43 A- 43 D  depicts a method of mixing a two part injectable substance (e.g., medication) for injection according to some embodiments. The multiple chamber injection system  4100  depicted in  FIGS.  43 A- 43 D  is similar to the multiple chamber injection system  4100  depicted in  FIGS.  41  and  42    and described above. One difference is that the system  4100  depicted in  FIGS.  43 A- 43 D  includes a dry component (e.g., lyophilized powder and/or solid, e.g., compressed powder) (not shown) in the distal chamber  4118  to be solubilized by the liquid  4132  to for the two part injectable substance. In  FIG.  43 A , the cap  4150  is removed from the needle coupling member  4156 . In  FIG.  43 B , a distally directed force from the plunger member  4138  and the proximal stopper member  4134  causes distal movement of the distal stopper member  4114 , which in turn causes the proximal end of the mix tube  4124  to pierce completely through the distal stopper member  4114  and drives the liquid  4132  from the proximal chamber  4116  to the distal chamber  4118 . In  FIG.  43 C , the system  4100  is shaken to mix the liquid  4132  in the distal chamber  4118  with the dry component (not shown) therein. In  FIG.  43 D , a needle  4166  is attached via a needle coupling member  4156  (e.g., male Luer connector) to prepare the system  4100  for injection. Without a venting/liquid restricting component, during the mixing in  FIG.  43 C , the increased pressure in the distal chamber  4118  may eject some of the liquid  4132  (and the solubilized dry component), reducing the accuracy and precision of the system  4100 . 
       FIG.  44    is a detailed view of the distal end of the syringe body  4110 , including a vent plug  4154  which is disposed at least partially in the needle coupling member  4156  and around a distal end of the mix tube  4124  according to some embodiments.  FIG.  45    is an even more detailed view of the distal end of the syringe body  4110 , including the vent plug  4154  according to some embodiments.  FIG.  45    shows that the vent plug includes a plurality of channels  4158 , which are configured (e.g., sized and shaped) to allow gases (e.g., air) to escape  4160  the interior of the syringe body  4110  (e.g., distal chamber  4118  see  FIG.  44   ), while preventing liquids from escaping the interior of the syringe body  4110 . 
       FIG.  46    is a detailed view of a vent plug  4154  for use in a multiple chamber injection system  4100  according to some embodiments. Many components of the system  4100  are omitted for clarity. The vent plug  4154  is disposed around a mix tube  4124  and includes a plurality of channels  4158 .  FIG.  47    is a detailed view of a vent plug  4154  for use in a multiple chamber injection system  4100  according to some embodiments.  FIG.  47    depicts the center opening  4162  of the vent plug  4154  through which a mix tube  4124  may be inserted.  FIG.  47    also depicts a plurality of channels  4158  that may be molded into an interior surface of the vent plug  4154 . The plurality of channels  4158  are configured (e.g., sized and shaped) to allow gases to escape/vent from the interior of the syringe body  4110  while preventing liquids from escaping the interior of the syringe body  4110 . Venting gases and releasing pressure from the interior of the syringe body  4110  minimizes unintended ejection of liquid from the interior of the syringe body  4110  and increases accuracy and precision of the system  4100 . Venting gases and releasing pressure from the interior of the syringe body  4110  also minimizes unintended proximal movement of the plunger member  4138  from back pressure, thereby eliminating the need for latches on the plunger member  4138  to prevent proximal movement thereof. 
       FIG.  48    depicts an alternative embodiment of the vent plug  4154  where the vent channels  4158  are present in an exterior surface of the vent plug  4154 . The vent plug  4154  is configured to be installed into the distal needle interface  4156  (see  FIG.  45   ), where the vent channels  4158  are in contact with the interior surface of the distal needle interface  4156 , maintaining the open vent channel  4158  to an exterior of the syringe body  4110 . The vent channels  4184  may be linear or may be non-linear with bends and turns along the longitudinal axis of the vent plug  4154  (as shown in  FIG.  48   ).  FIG.  48    illustrates vent channels  4184  that are non-linear, creating a tortuous path for fluid flow along the longitudinal axis of the vent plug  4154 . As fluid is forced through the vent channels  4158 , bends or corners in the vent channels  4158  provide impediments/resistance to fluid flow. These impediments are configured to take advantage of fluid frictional effects such that more viscous fluids (e.g., liquids) require higher pressure to flow through the vent channels  4158 . For example, gases (e.g., air) will flow through these vent channels  4158  at a predetermined pressure generated in the syringe body  4110 . Liquids (e.g., water or liquid drugs) require a higher pressure to flow through the vent channels  4158 . This pressure differential requirement for fluid flow provides a restriction to prevent water or liquid drug from being unintentionally expelled from the end of the syringe body  4110  during mixing (see  FIG.  43 C ) when the syringe cap  4150  is removed. The pressure for fluid flow may also be generated by shaking the syringe during mixing, such as g-forces from shaking applied over the surface of the liquid. The vent channels  4158  are configured such that high g-forces resulting from shaking the syringe during mixing do not apply a large enough force on the liquid to expel the liquid during shaking. The vent channels  4158  may be constructed to provide orifices for fluid flow, capillary channels, and/or high fluid friction surfaces to tailor the flow restriction for different fluids. This embodiment also depicts a central opening  4164  of the vent plug  4154  through which a mix tube  4124  may be inserted. The central opening  4164  may be disposed entirely through the vent plug or may be a blind hole with a bottom for locating the distal end of the mix tube  4124 . 
     Alternative Ratcheting/Anti-Retraction System 
     An alternative embodiment of the ratcheting/anti-retraction system is illustrated in  FIG.  41 ,  41 A and  49 - 56   . As shown in  FIGS.  41  and  49   , this ratcheting/anti-retraction system is configured for use with a plunger member  4138 ,  3516  having a smooth exterior. An anti-retraction feature  3321 ,  4090  (see 
       FIGS.  41 A and  42   ) includes at least one brake tab  3321 - 1 ,  4092 . The brake tab  3321 - 1 ,  4092  may be constructed from sheet metal, or a polymer material. Sheet metal brake tab  3321 - 1 ,  4092  may be configured to have sharp edges on the plunger member engaging surfaces  3329  which enable the brake tab  3321 - 1 ,  4092  to deform the exterior surface of the plunger member  4138 ,  3516 . The anti-retraction feature  3321 ,  4090  and intercoupled brake tabs  3321 - 1 ,  4092  may be configured to elastically deform upon insertion of the plunger member  4138 ,  3516  through the anti-retraction feature  3321 ,  4090 , deflecting the brake tabs  3321 - 1 ,  4092 . The elasticity of the brake tabs  3321 - 1 ,  4092  provides a biasing force which ensures there is contact between the plunger member engaging surfaces  3329  and the exterior of the plunger member  4138 ,  3516 . 
     The anti-retraction feature  3321 ,  4090  is inserted into a transverse slot  3323 ,  3584  in the finger flange  4136 ,  3580  with the brake tabs  3321 - 1 ,  4092  bent distally  3325 . Pre-bending the brake tabs  3321 - 1 ,  4092  allows the brake tabs  3321 - 1 ,  4092  to flex distally upon insertion of the plunger member  4138 ,  3516  into the finger flange  4136 ,  3580 , while preventing movement of the plunger member  4138 ,  3516  in a proximal direction. The amount of pre-bend may be between approximately 10 degrees and approximately 80 degrees, preferably 45 degrees per brake tab  3321 - 1 ,  4092 . Alternatively, the brake tab  3321 - 1 ,  4092  may be flat when inserted into the transverse slot  3323 ,  3584 , and may be bent upon insertion of the plunger member  4138 ,  3516  into the finger flange  4136 ,  3580 . Bearing surfaces/fit tabs  3321 - 2 ,  3596 ,  4096  on the anti-retraction feature  3321 ,  4090  are configured to engage the interior surfaces of the finger flange  4136 ,  3580  defining the transverse slot  3323 ,  3584  to react the forces applied to the brake tab  3321 - 1 ,  4092  from insertion of the plunger member  4138 ,  3516 . The anti-retraction feature  3321 ,  4090  may have retention barbs/tabs  3327 ,  3594 ,  4094  to hold the anti-retraction feature  3321 ,  4090  in the transverse slot  3323 ,  3584  in the finger flange  4136 ,  3580 . While the ratcheting systems herein are depicted and described for use with a dual chamber syringe the ratcheting systems may be used with any syringe or cartridge injection system where it is desired to prevent movement of the plunger member in the proximal direction. 
       FIGS.  49  to  56    depict the addition of a one-way ratchet to the dual chamber injection systems described herein (and in the other patent applications incorporated by reference herein). The one-way ratchet enables the plunger member to be moved distally with minimal drag force and prevents the plunger member from moving proximally by the engagement of ratchet teeth onto the outer surface of the plunger member. During the mixing phase of the multi-component injectable preparation air pressure accumulates in the distal chamber as the liquid is transferred. This pressure builds and produces a proximally directed reaction force on the user&#39;s thumb. The addition of a toothless ratchet counteracts this reaction force, preventing the plunger member from moving proximally. With the toothless ratchet engaged, the user does not need to continually apply a distally directed force to maintain plunger member position. The ratchet may be toothless, where the plunger member is smooth on the outside surface and the ratchet arms are configured to dig into the plunger member. In this case the position of the plunger member is maintained in infinitely small increments. Alternatively, the ratchet may engage with annular grooves in or threads on the outside surface of the plunger member, providing an incremental position stop. The annular grooves may provide a tactile and/or audible click or feedback to the user that the ratchet is engaged. 
       FIG.  49    depicts a dual chamber injection system  3500  with a finger flange  3580  having an anti-retraction feature  3590  according to some embodiments. The anti-retraction feature  3590  prevents proximal movement of the plunger member  3516  relative to the syringe body  3510 , while allowing distal movement. In addition to the syringe body  3510 , the plunger member  3516 , the finger flange  3580 , and the anti-retraction feature  3590 , the dual chamber injection system  3500  also includes proximal and distal stopper members  3512 ,  3514 , and a needle hub assembly  3570 . The injection system  3500  depicted in  FIG.  49    may also include a needle assembly  3530  which has a proximal and distal end. The proximal end is configured to have fluid passages (not shown, but see  FIG.  35    ( 3324 ),  FIG.  9 C  ( 885 ), and/or  FIG.  7 E  ( 270 )) for transferring fluid from the proximal chamber  3522  to the distal chamber  3524  when the plunger member  3516  is moved distally. The plunger member  3516  is inserted into an interior  3518  of the syringe body  3510  via a proximal opening in the syringe body. The proximal and distal stopper members  3512 ,  3514  together with the syringe body  3510  define a proximal drug chamber  3522 . The distal stopper member  3514  and the syringe body  3510  define a distal drug chamber  3524 . The plunger member  3516  may be manually manipulated to insert the proximal stopper member  3512  relative to the syringe body  3510 . If a non-compressible fluid is disposed in the proximal drug chamber  3522 , inserting the proximal stopper member  3512  also inserts the distal stopper member  3514  relative to the syringe body  3510 . 
       FIGS.  50  to  53    depict the finger flange  3580 , which is configured to be mounted onto a small flange  3511  formed at the proximal end of the syringe body  3510  (see  FIG.  53   ). As shown in  FIG.  50   , the finger flange  3580  defines a first recess  3582  configured to receive the small flange  3511  to couple the finger flange  3580  to the syringe body  3510 . The finger flange  3580  also defines a second recess  3584  configured to receive the anti-retraction mechanism  3590 . The anti-retraction mechanism  3590  includes a pair of brake tabs  3592  configured to provide an opposing force with proximal movement of the plunger member  3516  relative to the anti-retraction mechanism  3590 , while allowing distal movement. The opposing force may include a frictional force as the brake tabs  3592  contact an outer surface  3517  of the plunger member  3516  and a reaction force as the brake tabs  3592  dig into an outer surface  3517  of the plunger member  3516 . The acute angle of the brake tabs  3592  creates the reaction force parallel to the plunger member  3516 , exerted by a sharp curved edge of each of the brake tabs  3592  contacting the surface  3517  of the plunger member  3516 . This reaction force along with the frictional force prevents the plunger member  3516  from moving in the proximal direction. The finger flange  3580  further defines a “C” shaped opening  3586  configured to receive the plunger member  3516  (see  FIG.  50   ). Due to the “C” shaped opening  3586 , the finger flange  3580  can be slid onto the small flange  3511  from the side of the small flange  3511  after the plunger member  3516  is inserted during assembly. The “C” shaped finger flange  3580  and anti-retraction mechanism  3590  depicted in  FIGS.  49  to  53    can be slid/snapped on to the small flange  3511  of the syringe body  3510  after the plunger member  3516  is inserted. Syringe bodies  3510  with plunger members  3516  screwed into proximal stopper members  3514  are able to pack more tightly into shipping trays for transportation. The finger flange  3580  with is the anti-retraction mechanism  3590  is snapped after shipping, and snaps around both the syringe body  3510  and the plunger member  3516 . 
     As shown in  FIG.  51   , the anti-retraction mechanism  3590  is a generally “C” shaped clip. In some embodiments, the anti-retraction mechanism  3590  is cut or stamped from a sheet of metal and then certain portions thereof are bent to the final shape. The anti-retraction mechanism  3590  includes a pair of brake tabs  3592  configured to provide an opposing frictional force with proximal movement of the plunger member  3516  as described above. The brake tabs  3592  are the elastically deformable and self-energizing. The brake tabs  3592  extend at an acute angle in a distal direction relative to the plane of the anti-retraction mechanism  3590  (i.e., the brake tabs  3592  are bent downwards). The angle and elasticity of the brake tabs  3592  allows the plunger member  3516  to slide past the break tabs  3592  in the in distal direction. When the plunger member  3516  is pulled in a proximal direction relative to the brake tabs  3592 , the brake tabs  3592  make contact with and dig into an outer surface  3517  of the plunger member  3516  and prevent proximal plunger member  3516  movement relative to the break tabs  3592 . Because the brake tabs  3592  are self-energizing, with attempted proximal movement, the brake tabs  3592  engages with the plunger member  3516  by increasing a frictional force applied to the plunger member  3516  and an amount of digging into the plunger member  3516  to prevent its proximal movement. In effect, the brake tabs  3592  form a pair of pawls to engage the plunger member  3516  and prevent proximal movement thereof. In some embodiments, the plunger member (not shown) may have annular grooves threads and/or formed thereon to increase the ratcheting effect of the brake tabs  3592 . The anti-retraction mechanism  3590  and the brake tabs  3592  prevent removal of the plunger member  3516  from the dual chamber injection system  3500  after use. 
     The anti-retraction mechanism  3590  also includes a pair of retention tabs  3594  configured to hold the anti-retraction mechanism  3590  in the second recess  3584  of the finger flange  3580 . The retention tabs  3594  are bent inward so that they are configured to grip the inside of the second recess  3584  in the finger flange  3580  with a frictional force and a reaction force to prevent removal of the anti-retraction mechanism  3590  from the second recess  3584 . The retention tabs  3594  are also self-energizing to provide increasing frictional and reaction force as the anti-retraction mechanism  3590  is pulled from the second recess  3584 . In the embodiment depicted in  FIG.  52   , the finger flange  3580  includes a pair of openings  3588  configured to receive the retention tabs  3594  from the anti-retraction mechanism  3590  to retain the anti-retraction mechanism  3590  in the second recess  3584  by interference instead of friction. 
     As shown in  FIG.  51   , the anti-retraction mechanism  3590  also includes four fit tabs  3596  configured to reduce a tolerance between the second recess  3584  and the anti-retraction mechanism  3590  thereby providing a tighter fit of the anti-retraction mechanism  3590  in the second recess  3584 . The original tolerance is larger because, in some embodiments, the finger flange  3580  is molded from a polymer, and therefore has minimum size limitations for recesses that can be accurately and precisely formed therein. On the other hand, the anti-retraction mechanism  3590  is cut from a sheet of metal, and therefore has a thinner profile then the height of the second recess  3584 . The fit tabs  3596  increase the thickness/height of the anti-retraction mechanism  3590 , thereby providing a tighter fit in the second recess  3584 . The fit tabs  3596  also provide rigidity to the anti-retraction mechanism  3590 . Accordingly, when the plunger member  3516  is pulled proximally, the brake tabs  3592  (because of their elasticity and angle) exert an outward force on the anti-retraction mechanism  3590 . This outward force is transferred through the anti-retraction mechanism  3590  and the fit tabs  3596  to push against the inside of the second recess  3584  of the finger flange  3500  due to the rigidity of the anti-retraction mechanism  3590 . This outward force is the reactive force to the frictional and reaction forces applied to the plunger member  3516  to prevent its proximal movement. 
       FIGS.  54  to  56    depict a dual chamber injection system  4000  with a finger flange  4080  having an anti-retraction feature  4090  according to some embodiments. The dual chamber injection system  4000  has many of the same components as the dual chamber injection system  3500  depicted in  FIGS.  49  to  53    and described above. Those components have the same reference numerals as the corresponding components in the dual chamber injection system  3500 . The difference between the dual chamber injection systems  3500 ,  4000  is in the finger flanges  3590 ,  4090 . Unlike the finger flange  3590  depicted in  FIGS.  50  and  51   , which has a “C” shaped opening  3586  for receiving the plunger member  3516 , the finger flange  4090  depicted in  FIGS.  55  and  56    has an “O” shaped opening  4086  for receiving the plunger member  3516 . The “O” shaped opening  4086  provides an additional mechanism for preventing removal of the plunger member  3516  from the dual chamber injection system  4000  after use. 
     As shown in  FIG.  56   , the anti-retraction mechanism  4090  in the finger flange  4080  has an “O” and/or rectangular shape. The anti-retraction mechanism  4090  can be cut from a sheet of metal. Due to the “O” and/or rectangular shape of the finger flange  4080 , the finger flange  4080  is snapped onto the small flange  3511  from a proximal direction during assembly. Then the plunger member  3516  is inserted through an “O” shaped opening  4086  in the finger flange  4080 . The “O” shaped opening  4086  in the finger flange  4080  also aligns the plunger member  3516  in the syringe body  3510 . 
     The brake tabs  4092  in the anti-retraction mechanism  4090  depicted in  FIG.  56    are identical to the brake tabs  3592  in the anti-retraction mechanism  3590  depicted in  FIG.  51   , which are described above. The retention tab  4094  in the anti-retraction mechanism  4090  depicted in  FIG.  56    are similar to the retention tabs  3594  in the anti-retraction mechanism  3590  depicted in  FIG.  51   , which are described above. The difference is that there is a single retention tab  4094  in anti-retraction mechanism  4090 , while there is a pair of retention tabs  3594  in anti-retraction mechanism  3590 . The fit tabs  4096  in the anti-retraction mechanism  4090  depicted in  FIG.  56    are similar to the fit tabs  3596  in the anti- retraction mechanism  3590  depicted in  FIG.  51   , which are described above. The difference is that there are three fit tabs  4096  in anti-retraction mechanism  4090 , while there are four fit tabs  3594  in anti-retraction mechanism  3590 . 
     The anti-retraction mechanism  4090  depicted in  FIGS.  54  to  56    is symmetrical, simplifying high volume assembly whether manual or automated. In embodiments where the plunger member (not shown) has annular grooves and/or threads, the anti-retraction mechanism  4090  may prevent removal of plunger member  3516  from the dual chamber injection system  4000 . Further, the pair of long beams in the “O” shaped anti-retraction mechanism  4090  are deformable, allowing the anti-retraction mechanism  4092  bow outward, thereby transferring an outside reactive force to the interior walls of the second recess  4084  via the outside/long fit tabs  4096 . 
     While the prefilled dual chamber safety injection systems depicted and described herein include syringes with staked needles, the injection configurations and detent dual chamber configurations described herein can be used with cartridges an auto injector, and injection systems with Luer connectors, transfer pipes, and no needles such as those described in U.S. Utility patent application Ser. Nos. 15/801,281 and 15/801,259, which were previously incorporated by reference herein. 
     Various exemplary embodiments of the invention are described herein. Reference is made to these examples in a non-limiting sense. They are provided to illustrate more broadly applicable aspects of the invention. Various changes may be made to the invention described and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process act(s) or step(s) to the objective(s), spirit or scope of the present invention. Further, as will be appreciated by those with skill in the art that each of the individual variations described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present inventions. All such modifications are intended to be within the scope of claims associated with this disclosure. 
     Any of the devices described for carrying out the subject diagnostic or interventional procedures may be provided in packaged combination for use in executing such interventions. These supply “kits” may further include instructions for use and be packaged in sterile trays or containers as commonly employed for such purposes. 
     The invention includes methods that may be performed using the subject devices. The methods may comprise the act of providing such a suitable device. Such provision may be performed by the end user. In other words, the “providing” act merely requires the end user obtain, access, approach, position, set-up, activate, power-up or otherwise act to provide the requisite device in the subject method. Methods recited herein may be carried out in any order of the recited events which is logically possible, as well as in the recited order of events. 
     Exemplary aspects of the invention, together with details regarding material selection and manufacture have been set forth above. As for other details of the present invention, these may be appreciated in connection with the above-referenced patents and publications as well as generally known or appreciated by those with skill in the art. For example, one with skill in the art will appreciate that one or more lubricious coatings (e.g., hydrophilic polymers such as polyvinylpyrrolidone-based compositions, fluoropolymers such as tetrafluoroethylene, PTFE, hydrophilic gel or silicones) may be used in connection with various portions of the devices, such as relatively large interfacial surfaces of movably coupled parts, if desired, for example, to facilitate low friction manipulation or advancement of such objects relative to other portions of the instrumentation or nearby tissue structures. The same may hold true with respect to method-based aspects of the invention in terms of additional acts as commonly or logically employed. 
     In addition, though the invention has been described in reference to several examples optionally incorporating various features, the invention is not to be limited to that which is described or indicated as contemplated with respect to each variation of the invention. Various changes may be made to the invention described and equivalents (whether recited herein or not included for the sake of some brevity) may be substituted without departing from the true spirit and scope of the invention. In addition, where a range of values is provided, it is understood that every intervening value, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. 
     Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. Reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in claims associated hereto, the singular forms “a,” “an,” “said,” and “the” include plural referents unless the specifically stated otherwise. In other words, use of the articles allow for “at least one” of the subject item in the description above as well as claims associated with this disclosure. It is further noted that such claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. 
     Without the use of such exclusive terminology, the term “comprising” in claims associated with this disclosure shall allow for the inclusion of any additional element--irrespective of whether a given number of elements are enumerated in such claims, or the addition of a feature could be regarded as transforming the nature of an element set forth in such claims. Except as specifically defined herein, all technical and scientific terms used herein are to be given as broad a commonly understood meaning as possible while maintaining claim validity. 
     The breadth of the present invention is not to be limited to the examples provided and/or the subject specification, but rather only by the scope of claim language associated with this disclosure.