Injection delivery system for biologics and drugs

Abstract

Briefly, an injection delivery system is described for subcutaneous or intramuscular injection of a drug, in particular a large volume of a biologic drug, high and low viscosity biologies, or a large volume of a high viscosity and low viscosity chemical drug. The injections may be self-administered or performed by a caregiver. The system uses a pump to move a drug from a vial, thorough an infusion set, and into the patient. A vial of a biological or chemical drug is set into a vial adapter that is associated with the pump, which can be manual or powered. A fluidics subassembly connects the vial adapter, pump, and the infusion set so that a drug pathway is enabled from the vial to the patient. The fluidics subassembly has one or more check valves to assure that the drug pathway is only enabled for a one-way drug flow out of the vial and to the patient. The infusion set has flexible tubing that connects the fluidics subassembly to cannula assembly inside an infuser housing. The cannula assembly has an air evacuation assembly near the tip of the needle. This air evacuation assembly is constructed to safely exhaust air from the cannula assembly at three times: (1) at initial setup to exhaust air while the drug is filling the cannula assembly, which enables the self-priming; (2) during injection to exhaust drug-entrapped air, which increases injection safety; and (3) at the end of drug delivery to exhaust air after the full dose of drug has been delivered to the cannula assembly, including drug that was in the tubing, which reduces wasted drug and minimizes the amount of drug overfill required in the vial.

Description

Injection Delivery System for Biologies and Drugs

[0001] Related Applications

[0002] This application claims priority to U.S. provisional application number 63 / 634,632, filed April 16, 2024, entitled “Large Volume / High Viscosity Subcutaneous Biologies Delivery System,” and to U.S. provisional application number 63 / 721,091, filed November 15, 2024, entitled “Large Volume / High Viscosity Subcutaneous Biologies Delivery System,” both of which are incorporated herein as if set forth in their entirety.

[0003] Field of the Invention

[0004] The field of this invention is medical devices and methods for subcutaneous or intramuscular injection of (1) a large volume of a biologic drug (large molecule); (2) a high viscosity biologic drug or chemical drug; or (3) large volume of a chemical drug (small molecule).

[0005] Background

[0006] Therapeutics, such as biologies (large molecule) and chemical drugs (small molecule), are often administered to patients as part of the prevention or healing process. Sometime these drugs are administered using an IV, which uses a needle to inject the drug directly into a vein of a patient. As IV’ s are inconvenient, expensive, and time consuming, it is preferable to formulate the drug so it can be injected into a patient’s tissue using a syringe and needle. There are two common ways to inject a drug. First, the drug may be injected subcutaneously, where the needle of the syringe is inserted a few millimeters (e.g. 6-8) into a fatty layer just under the skin and above the muscle. This subcutaneous layer has relatively few blood vessels, so absorption is relatively slow. For many therapeutic drugs, subcutaneous injection is the preferred method. Second, the drug may be administered using an intramuscular injection. An intramuscular injection involves delivering medication deep into the muscle tissue, where it is absorbed more quickly into the bloodstream. Accordingly, a longer needle is needed for an intramuscular injection as compared to a subcutaneous injection.

[0007] A biologic drug is made of large molecules and is typically manufactured in concentrations of up to approximately 100-200 mg / ml. Biologic drugs are typically subcutaneously administered in doses of 2 ml or less by syringe injection, often with the use of an autoinjector, and sometimes have volumes up to about 5 ml. If a patient needs more than that,then multiple injections can be given, or a patch pump can be used, as there is currently no autoinjector that can inject high volumes (greater than about 5 ml) of a biologic drug in one injection. In order to reduce the volume of a biologic drug that must be administered, it may be manufactured in a higher concentration. Such a high concentration dose has a higher viscosity as compared to the standard biologic, making it even more difficult to administer.

[0008] Biologies are drugs or vaccines made from a living organism. A biologic can be made from proteins, sugars, DNA, cells or living tissue, for example. The source may be human, animal or a microorganism (like a bacteria or virus). Biologies may be difficult to make and are generally much more expensive than small molecule drugs. One year of treatment with a biologic may cost well over $100,000. Biologic molecules are large and may have thousands of atoms, making them much more complex. A patient may require a biologic, like gene or protein therapy, to treat diseases such as cancer or arthritis, especially if conventional drugs prove ineffective or have adverse side effects or if biologies offer better results. Hormones like insulin are also considered biologies. Additionally, biologies can be used as vaccines to prevent diseases, like the vaccine for human papillomavirus (HPV) that helps prevent cervical cancer.

[0009] Large molecule (biologic) drugs are becoming increasingly prevalent in areas such as oncology, rheumatology, dermatology, and other areas with inflammatory diseases due to their effectiveness, specificity, and favorable safety profiles. Many biologies are delivered intravenously in hospitals or clinics, but new formulations have enabled subcutaneous delivery, with the advantages of convenient in-home administration, improved patient experience, reduced treatment burden, lower healthcare costs, and a reduction in serious infusion reactions. Some formulations enable relatively small delivery volumes (1 ml or less), making them compatible with needle safety devices for delivery by nurses, or readily available autoinjectors, which are convenient for caregivers or patient self-administration. Both of these options are low in cost.

[0010] A standard injectable chemical drug is made of small molecules. Chemical drugs are small molecules made up of a limited number of atoms, for example, dozens of atoms.Generally, such a standard chemical drug is most often given in pill form, but sometimes will be subcutaneously administered in doses of 2 ml or less by syringe injection, often with the use of an autoinjector, and sometimes have volumes up to about 5 ml. If a patient needs more than that, then multiple injections must be given, as there is currently no autoinjector that can inject high volumes (greater than 5 ml) of a standard chemical drug in one injection. In order to reduce the volume of a standard drug that must be administered, the small molecule chemical drug may bemanufactured in a higher concentration. Such a high concentration dose has a higher viscosity as compared to the standard drug, or is in the form of a suspension, making it much more difficult to administer.

[0011] Autoinjectors are not usable for high volume or high viscosity drug delivery. Recently, autoinjectors have been successful delivering volumes of a biologic up to 2 ml subcutaneously. However, many biologies require large volumes (5 ml or more), making autoinjectors impractical and unusable. This is also applicable to some chemical drugs such as chemotherapeutics that are being reformulated for subcutaneous delivery. Combining high- concentration / high-viscosity formulations with a device such as an autoinjector can be challenging given the increased force required to administer the fluid within an acceptable injection time while meeting usability requirements.

[0012] Further, autoinjectors with prefilled syringes as the primary container are classified as “combination products” by the FDA, making their development complex and adding considerable time and expense to the development process. Pharmaceutical companies would prefer to provide their biologies in vials without a delivery device, avoiding the added complexity, expense, and time involved in developing and manufacturing a drug-device combination product.

[0013] The manual syringe push is not practical. One existing solution for subcutaneous delivery of large volume or high viscosity biologies is a syringe push, where the drug is injected directly with a syringe and needle or through a subcutaneous infusion set with tubing. This approach requires a trained nurse to transfer the biologic from the vial to the syringe, attach the needle or infusion line, prime the system, insert the needle or infusion set, and perform the injection. This process is neither patient nor user friendly, negating many of the potential benefits of subcutaneous infusion. The manual syringe push occupies the nurse’s time for several minutes, can be awkward for both the nurse and patient, can be difficult due to high forces required to perform the injection (large syringe diameter), wastes a significant amount of drug that is trapped in the tubing after delivery, and is challenging to maintain needle position when the syringe is used without an infusion set. It can also result in the medication being delivered to the wrong area or at the wrong depth since needle position is controlled manually when an infusion set is not used. As a last resort, the manual syringe push can be used to get a large volume biologic into a patient subcutaneously.

[0014] Patch pumps are expensive and impractical for biologic subcutaneous delivery. Patch pumps are a well-known drug delivery device approach that enables drug delivery in areas where the patch can be applied to the skin. One example of a patch pump is a wearable electronic insulin pump that a patient adheres to his or her skin. A flexible cannula is inserted under the skin, and the patient uses a controller to wirelessly operate the pump to inject insulin as needed. Since insulin is a highly potent drug, patch pumps typically contain up to about 2 ml of drug which is delivered as needed over several days. Larger volume patch pumps up to 10 or 20 ml have been developed to deliver large doses of biologies within a few minutes.

[0015] Some pharmaceutical companies have developed such patch pumps, which are typically single-use complex electro-mechanical devices that attach to the patient’s skin to deliver the drug. These devices are expensive (10s to 100s of millions of dollars, beyond the reach of some pharmaceutical companies) and time-consuming (years) to develop, high in end cost, can be unreliable (can produce wet / partial injections or fail to deliver the drug entirely), are complex, non-intuitive, not patient friendly (people do not want large devices adhered to their bodies) and generate considerable mixed biologic electro- mechanical waste. Some patch pumps use custom primary containers which are also expensive, difficult to develop, and may require custom filling equipment. Patch pumps are essentially “black boxes” where the status and functionality of the system are not apparent to the user, even with added lights, sounds, and displays which increase complexity and often cause confusion rather than clarification.

[0016] A patch pump can be used to deliver a higher volume of a drug as compared to a regular needle injection, but the patch pump is an expensive electro-mechanical device that can be hard to set up properly and can be confusing to operate. Further, a patch pump is not able to effectively deliver high viscosity biologies, which can require substantial pressures to inject. In addition, like autoinjectors, patch pumps are classified as drug-device “combination products” by the FDA, making their development complex and adding considerable time and expense to the development process. Pharmaceutical companies would prefer to provide their biologies in standard vials without the added complexity, expense, and time involved in developing, manufacturing, and gaining regulatory approval for a delivery device.

[0017] Hyaluronidase is expensive and may not be accessible. Hyaluronidase is an enzyme that makes it easier to inject large volumes subcutaneously. To use, the Hyaluronidase is first injected at the injection site where it acts to make the patient’s tissue more sponge-like. This enables the modified tissue to more readily accept higher volumes of a biologic. Hyaluronidasemay also be co-formulated with the intended biologic, but this may be challenging. Further, Hyaluronidase is expensive and it can be difficult to obtain the necessary use licenses.

[0018] The Subcutaneous Drug Delivery & Development Consortium is an industry group that was formed to collaboratively advance and transform patient care and improve patient outcomes by leading fundamental advancements in subcutaneous drug development and delivery. As such, this group developed problem statements and goals for subcutaneous delivery (in priority order) as shown directly below:• High dose / volume• Bioavailability• Patient preference: IV vs. SC• Clinical trial strategy• Payer preference• Patient experience & discomfort• Patient-physician interactions

[0019] In this way, the Subcutaneous Drug Delivery & Development Consortium has clearly set out the needs and goals for advanced subcutaneous biologies and illuminates the many shortfalls and long-felt needs in current devices and methods.

[0020] As indicated above, high dose / high volume delivery is the highest priority need. Thus, there is a need for a simple, reliable, low development and end user cost, intuitive, user-friendly device for self-admini strati on of large volume / high viscosity biologies. Ideally, this device would be compatible with different biologies with no or minimal modifications, and would not require development, co-packaging, or cross-labeling with the biologic (i.e., provide an option to not classify as a combination product in the US). Known devices have proven ineffective in enabling self-administration in many environments. For example, although autoinjectors allow for patient-self administration, they are unable to administer high volumes; patch pumps are intended to fill this gap, but have failed as previously described; and syringes are not effective in most cases for patient self-administration.

[0021] Vials. Vials are a favored primary container for pharmaceutical companies due to various available sizes, simplicity, and experience / familiarity with the vial platform and fill / finish processes and equipment. Drugs / biologics are typically extracted from a vial using asyringe and needle. This requires training and is typically performed by nurses and not patients / caregivers.

[0022] Summary of the Invention

[0023] The described Injection Delivery System is constructed for subcutaneous or intramuscular injection of a drug into a patient. In a key embodiment, the Injection Delivery System is able to administer a large volume of a biologic drug, and it can be designed to accommodate high and low viscosity biologies. In another embodiment, the Injection Delivery System may be used to administer a large volume of a chemical drug, and it works equally well on both high viscosity and low viscosity chemical drugs. Advantageously, the injections may be self-administered or performed by a healthcare professional.

[0024] The patient or health care professional uses a pump to move a drug from a vial, thorough an infusion set, and into the patient. More particularly, a vial of a biologic or chemical drug is set into a vial adapter that is associated with the pump. In one embodiment, a manual pump is a standard medical syringe. It will be understood that other pumps may be used, such as an electrically powered fluid pump, such as a medical infusion pump, which may be powered by batteries or connection to an electrical outlet. It will be appreciated that infusion pumps may be for example, an infusion syringe pump. A fluidics subassembly connects the vial adapter, syringe, and the infusion set so that a drug pathway is enabled from the vial to the patient. The fluidics subassembly has one or more check valves to assure that the drug pathway is only enabled for a one-way drug flow out of the vial and to the patient.

[0025] The infusion set has flexible tubing that connects the fluidics subassembly to a cannula assembly inside an infuser housing. The cannula assembly has an air evacuation assembly near the tip of the needle. This air evacuation assembly is constructed to safely exhaust air from the cannula assembly at three times: (1) at initial setup to exhaust air while the drug is filling the cannula assembly, which enables the Injection Delivery System to be self-priming; (2) during injection to exhaust drug-entrapped air, which increases injection safety; and (3) at the end of drug delivery when the vial is empty, the manual pump begins delivering air to the cannula assembly, displacing drug in the tubing, thus reducing wasted drug and minimizing the amount of drug overfill required in the vial.

[0026] The air evacuation assembly has a small chamber that receives air or drug from an input port, depending what stage the injection is at. The chamber also has an air vent at its top side anda needle port for connecting a medical needle. The air vent has a hydrophobic membrane, and the needle port has one or more restrictors for causing the drug to increase pressure in the chamber. The restrictors may be, for example, one or more of check valves, flow restrictors, or membranes. The hydrophobic membrane and the drug restrictors are selected and sized such that there is a lower pressure air path enabled from the chamber to the air vent, as compared to the air pressure required for air to exit the needle. In operation, air that flows into the chamber will be safely exhausted as the cannula assembly is priming. As drug continues to fill the chamber, pressure in the chamber rises, and when the drug pressure exceeds the restriction pressure, the drug begins flowing into the needle port and needle. No drug can exit the air vent, as it is covered by a hydrophobic membrane. As such, the Injection Delivery System is safely selfpriming.

[0027] As drug delivery completes, the tubing empties of drug, and air then starts moving into the chamber. Once enough air has entered the chamber so that air begins venting from the chamber’s air vent, the pressure in the chamber begins to drop. When the pressure in the chamber has dropped to be below the restriction pressure, then the drug stops flowing out the needle port and needle. In this way, air pumped into the chamber is safely exhausted, and no harmful amount of air is injected into the patient. With the use of the air evacuation assembly, the vial, syringe, and tubing can be fully evacuated, and the only drug that is wasted is the small amount left in the chamber, needle port, and needle. This reduces the amount of overfdl required in the vial to ensure that the labeled dose is delivered to the patient, thus reducing costs.

[0028] In one embodiment of the Injection Delivery System, the infuser has a clear, transparent or translucent base that enables the patient or health care worker to see the status of an internal lock ring. If the ring is not visible, then it indicates the infuser has not been used. If the ring is visible, then it indicates the infuser has been used and should be disposed of. A brightly colored lock ring makes an efficient and effective safety indicator for the infuser. Also, the lock ring can be constructed to assure the carriage of the infuser can only be fully depressed one time.

[0029] Brief Descriptions of the Drawings

[0030] Fig. l is a diagrammatic illustration of a biologic / drug delivery system in accordance with the present invention.

[0031] Fig. 2 is a schematic illustration of a biologic / drug delivery system in accordance with the present invention.

[0032] Fig. 3A is an illustration of a biologic / drug delivery system in accordance with the present invention.

[0033] Fig. 3B is a diagrammatic illustration of a biologic / drug delivery system in accordance with the present invention.

[0034] Fig. 4 is a diagrammatic illustration of steps in using a biologic / drug delivery system in accordance with the present invention.

[0035] Fig. 5 is a flowchart of steps in using a biologic / drug delivery system in accordance with the present invention.

[0036] Fig. 6 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0037] Fig. 7 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0038] Fig. 8 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0039] Fig. 9 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0040] Fig. 10 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0041] Fig. 11 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0042] Fig. 12 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0043] Fig. 13 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0044] Fig. 14 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0045] Fig. 15 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0046] Fig. 16 is a schematic illustration of a vial adapter for use in a biologic / drug delivery system in accordance with the present invention.

[0047] Fig. 17 is a schematic illustration of a syringe pump system for use in a biologic / drug delivery system in accordance with the present invention.

[0048] Fig. 18 is a schematic illustration of a syringe pump system for use in a biologic / drug delivery system in accordance with the present invention.

[0049] Fig. 19 is a schematic illustration of a syringe pump system for use in a biologic / drug delivery system in accordance with the present invention.

[0050] Fig. 20 is a schematic illustration of a syringe pump system for use in a biologic / drug delivery system in accordance with the present invention.

[0051] Figs. 21 A and 21B are schematic illustrations of a fluidics subsystem for use in a biologic / drug delivery system in accordance with the present invention.

[0052] Fis. 22 is a schematic of operating a fluidics subsystem for use in a biologic / drug delivery system in accordance with the present invention.

[0053] Fig. 23 is a schematic illustration of a fluidics subsystem for use in a biologic / drug delivery system in accordance with the present invention.

[0054] Fig. 24 is a flowchart showing operation of a fluidics subsystem for use in a biologic / drug delivery system in accordance with the present invention

[0055] Fig. 25 is a diagrammatic illustration of a biologic / drug delivery system in accordance with the present invention.

[0056] Fig. 26 is a diagrammatic illustration of an infusion set for use in a biologic / drug delivery system in accordance with the present invention.

[0057] Fig. 27A is an exploded view of an infusion set for use in a biologic / drug delivery system in accordance with the present invention.

[0058] Fig. 27B are isometric and simplified views of an infuser for use in a biologic / drug delivery system in accordance with the present invention.

[0059] Fig. 27C is an isometric view of an infuser for use in a biologic / drug delivery system in accordance with the present invention

[0060] Figs. 28A-C are diagrammatic illustrations of a cannula assembly for use in a biologic / drug delivery system in accordance with the present invention.

[0061] Figs. 29A-C are diagrammatic illustrations of a cannula assembly for use in a biologic / drug delivery system in accordance with the present invention.

[0062] Fig. 30 is a flowchart of self-priming of a cannula assembly for use in a biologic / drug delivery system in accordance with the present invention.

[0063] Fig. 31 is a flowchart of avoiding overfill using a cannula assembly for use in a biologic / drug delivery system in accordance with the present invention.

[0064] Fig. 32 is a schematic illustration of a syringe pump system for use in a biologic / drug delivery system in accordance with the present invention.

[0065] Detailed Description

[0066] Referring now to Figs. 1 and 2, a biologic / drug delivery system 100 / 200 is illustrated. Generally, a biologic / drug delivery system 100 / 200 is constructed to allow for a patient, caregiver, or healthcare professional to manually administer high-volume or high-viscosity infusions of a drug or biologic in a simple and cost-effective manner. In operation, the user withdraws the drug or biologic from a primary container vial 105 / 205 (supplied separately or provided along with the device but not pre-attached) and manually administers it via a syringe pump 101 / 201, which in some cases can include a standard medical syringe.

[0067] The biologic / drug delivery system 100 / 200 is intended to deliver by injection (1) a large volume of a biologic drug (large molecule); (2) a high viscosity biologic drug or chemical drug; or (3) large volume of a chemical drug (small molecule). As used herein, when referring to a drug for injection by the biologic / drug delivery system, “drug” shall mean each of (1) a large volume of a biologic drug (large molecule); (2) a high viscosity biologic drug or chemical drug; or (3) large volume of a chemical drug (small molecule). Further, although the preferred embodiment primarily uses and describes examples of subcutaneous injections, it will be understood that the drug delivery system may use an infusion set constructed for intramuscular injections.

[0068] Viscosity is a fluid property that is a measurement of the rate-dependent resistance to a change in movement. Informally, viscosity is an indicator of the relative thickness of a fluid, as well as an indicator of how much pressure will be required to move the fluid through a tube or passageway, or needle. Viscosity is measured in Centipoise (cP), where a cP=l is the viscosity of water. Many small molecule chemical drugs will be in range of 1-5 cP, and so can be moved through an injector needle or syringe without undue pressure. As the viscosity of the small molecule drug increases, for example to 10-15 cP, it becomes increasingly more difficult to inject through standard injection needles with standard syringes. Although biologic viscosities are normally fairly low when formulated at lOOmg / ml or less, higher concentrations lead to higher viscosities. As a result, biologies are sometimes formulated to be quite viscous, which requires substantial pressure for injection.

[0069] The biologic / drug delivery system 100 / 200 is enabled to deliver a biologic. A treatment may require a biologic, like gene or protein therapy, to treat diseases such as cancer or rheumatoid arthritis, especially if conventional drugs prove ineffective or if biologies offer better results. Hormones like insulin are also considered biologies. Additionally, biologies can be used as vaccines to prevent diseases, like the vaccine for human papillomavirus (HPV) that helps prevent cervical cancer. It will be understood that not all components are visible or viewable in both Fig. 1 and Fig. 2.

[0070] The biologic / drug delivery system 100 / 200 can also deliver a large volume of a standard chemical drug. The biologic / drug delivery system 100 / 200 can be used to make a single delivery of a high volume of a standard drug, which is generally considered any single dose of greater than 5 ml. To reduce the volume of standard drug that must be administered, the small molecule chemical drug may be manufactured in a higher concentration. Such a high concentration dose has a much higher viscosity as compared to the standard drug, or is in the form of a liquid suspension, so it is difficult to administer as described earlier. The biologic / drug delivery system 100 / 200 can easily and reliably make a single delivery of a high viscosity standard drug.

[0071] An infusion set 130 / 230. The infusion set 130 / 230 has an infuser 131 / 231 that attaches to a patient at a target infusion site using an adhesive patch. It will be understood that an infusion set includes an infuser (attaches to the patient), infuser tubing, and the connectors necessary to connect the infuser to a syringe pump. When the infusion set 130 / 230 is activated at the infusion site, a needle 133 / 233 is subcutaneously inserted into the patient's infusion site. Once the needle 133 / 233 is inserted into the patient, the syringe 101 / 201 may be used to manually pump the drug or biologic through the tubing 127 / 227, to the fluid input port 135 / 235 and through the needle 133 / 233 into the patient. A vent 139, such as a hydrophobic vent, may be associated with the infusion set 130 / 230 to safely vent air from the tubing so that it is not injected into the patient. The hydrophobic vent 139 has a hydrophobic membrane, which repels water and compounds that are mixed with water. In this way, a hydrophobic membrane allows air to pass through but will restrict the flow of any water-based compound.

[0072] A vial pump housing 203. The vial pump housing 203 is used to securely hold the vial 105 / 205 and the syringe 101 / 201 during use, as well as to house subsystems for managing drug / biologic flow and air pressure equalization. The vial pump housing 203 has a vial adapter 211 that receives a standard drug vial 105 / 205, and has needles and tubing sufficient to enablewithdrawal of the drug or biologic from the vial 105 / 205 as well as to allow air to enter the vial 105 / 205 to equalize internal vial 105 / 205 pressure. The vial pump housing 203 also has a syringe adapter 102 / 202 for receiving and holding the syringe 101 / 201.

[0073] A syringe 101 / 201, such as a standard medical syringe. The syringe 101 / 201 acts as a manual pump that a patient or health care professional can use first to withdraw a portion of the drug or biologic from the vial 105 / 205 (pull up on syringe handle), and then to pump the portion of the biologic to the infuser 131 / 231, through the needle 133 / 233 and into the patient’s infusion site (push down on syringe handle). It will be understood that in some cases a single pull and push of the plunger rod 133 of syringe 101 / 201 may deliver the entire drug / biologic dose from vial 105 / 205 to the infusion set 130 / 230, but that in many cases it will take multiple pulls and pushes of the syringe 101 / 201 to fully deliver the entire drug or biologic dose into the patient. It will also be understood that although syringe 101 / 201 is shown as a standard medical syringe 101 / 201, that other custom constructions may be used. It will be appreciated that there may be an advantage to using a small syringe with multiple pulls and pushes as the syringe diameter is smaller, so higher pressures can be generated for the same applied force. As a result, the user can administer higher viscosity drugs with less force. Further, the syringe system 101 / 201 could be powered or otherwise automated. It will also be understood that a different human-powered pumping system could be used, such as a compressible bladder, a pipette bulb, or a handoperated peristaltic pump. The syringe has a plunger rod 153 that has a plunger seal 155 at its distal end. The plunger seal 155 provides a seal against the wall of the syringe 101 such that fluids will not leak, and enables positive and negative, pressures to be generated.

[0074] A vial adapter 211. The vial adapter 211 is positioned in the vial pump housing 203 and is sized and constructed to receive and hold a standard drug vial 105 / 205. The vial adapter 211 also has needles and tubing sufficient to enable withdrawal of the drug or biologic from the vial 105 / 205 as well as to allow air to enter the vial to equalize internal vial 105 / 205 pressure. For example, the vial adapter 211 may incorporate one or more air vents 115 that are connected with tubing 112 to inside the vial 105 / 205. Such an air vent could be used to maintain proper air pressure inside vial 105 / 205 while fluid is being withdrawn. The vial adapter 211 may also incorporate one or more fluid check valves 109 / 209 to assure that fluid can be withdrawn from the vial 105 / 205 under negative pressure, but that fluid is not improperly pushed into the vial 105 / 205 when the syringe 101 / 201 is providing a positive pressure. It will be understood thatcertain components, such as check valves and vents, may be alternatively positioned in the vial adapter 211 or in the fluidic subassembly 206 (discussed below).

[0075] A fluidics subassembly 206. The fluidics subassembly 206 is held in the vial pump housing 203 and is used first to safely transport the drug or biologic from vial 105 / 205 into the syringe 101 / 201 reservoir 151 / 251 where the fluid is held temporarily. Then, the fluidics subassembly 206 is used to safely transport the biologic fluid from the syringe 101 / 201 reservoir 151 / 251 to the infuser 131 / 231, and finally to the infusion site. The fluidics subassembly 206 may have vents, check valves, filters, flow restrictors or pressure buffers that control and manage the flow of the drug, biologic or air for the biologic infusion system 100 / 200, for example, by purging air bubbles and limiting pressure spikes. As will be fully discussed later, the fluidics subassembly 206 may have check valves, such as check valve 109 / 209 and check valve 125 / 225, which cooperate to assure that fluid can be withdrawn from the vial 105 / 205, but that fluid is not improperly pushed into the vial 105 / 205 when the syringe 101 / 201 is pressurized. The fluidic subassembly 211 may also have air vents and filters according to application specific requirements. The fluidics subassembly has an output port 221 that fluidically couples to a flexible tube 227. It will be understood that certain components, such as check valves and vents, may be alternatively positioned in the vial adapter 211 or in the fluidic subassembly 106 / 206. It will be understood that in some cases a flow restrictor or pressure buffer may be used to create a pressure drop in the system as a method for mitigating an overpressure scenario. They can be used to control how much force the user needs to exert on the plunger to deliver the drug at a given rate. Controlling flow rate allows for control of system pressure, which may be important for the correct function of filters, vents and valves.

[0076] In operation, it is possible that a particle in the drug or biologic could be caught in a check valve and keep that check valve in a constant open position (a leaky valve). To avoid the consequences from a propped-open check valve, it will be understood that 2 or more check valves could be used in a serial arrangement, such that if one check fails to operate correctly, then 1 or more operational check valves are still in the drug or fluid path to maintain proper function of the system.

[0077] Air evacuation assembly. In some embodiments, the biologic / drug delivery system 100 / 200 will have an air evacuation assembly (not illustrated) that provides two desirable functions. First the air evacuation assembly enables the biologic / drug delivery system 100 / 200 to be self-priming. That is, the patient or health care worker can fully set up the biologic / drugdelivery system, including subcutaneously setting the needle into the patient’s infusion site. The patient or health care worker may then begin moving the plunger rod 153 / 253 to the syringe 101 / 201 up and down, which acts to move drug or biologic from the vial 105 / 205 toward the infuser 131 / 231. Normally, the health care worker would be required to prime the tube leading to the needle to avoid injecting dangerous levels of air into the patient. However, the new biologic delivery system 100 / 200 may have an air evacuation assembly near the inlet to the needle. This air evacuation assembly enables air to harmlessly escape to the environment until the tube and fluid assemblies are full of the drug or biologic. At that time, the air evacuation assembly then directs the drug or biologic into the needle. In this way, only a trivial amount of air is injected into the patient. As a result, the biologic / drug delivery system is self-priming. In one example, the air evacuation assembly includes a hydrophobic air vent 139 near the inlet to the needle. It will be understood that alternative placements may be used to reduce the amount of air that could be injected into the patient.

[0078] Infusion tubing 127 / 227. A flexible medical grade tubing 127 / 227 is used to fluidically couple the fluidics subassembly 206 to the input port 135 / 235 of the infuser 131 / 231. In some cases, the tubing 127 / 227 may be disconnectable from either or both the fluidics subassembly 206 or the infuser 131 / 231.

[0079] Referring now to Figs. 3 A and 3B, a specific embodiment of a biologic / drug delivery system 300 is illustrated. Both Fig. 3A and Fig. 3B show the same biologic / drug delivery system 300, but in different illustrative formats. Figs. 3A and 3B may refer to structures introduced with reference to Fig. 1 and Fig. 2, as these structures and not visible. The biologic / drug delivery system 300 has a vial infusion housing 303 that has a wide base 304 for additional stability. It will be understood that a wide variety of shapes, materials, and configurations may be used in constructing the vial infusion housing 303. The vial infusion housing 303 is constructed and sized to hold a standard drug or biologic vial 305. It will be understood that vials may be provided in different sizes, shapes, and designs as needed for the specific drug / biologic. It will be understood that the vial infusion housing may be adapted to a wide variety of vials. As is typical, the vial 305 has a glass or plastic bottom, and has a top that has a puncturable seal that enables the biologic or drug to be withdrawn, and in some cases permits the injection of air or other gas to equalize pressure. It will also be understood that air can also be pulled into the vial by the vacuum that is created when liquid is drawn out of the vial. As illustrated, the vial 305 is held securely in an inverted position, such that the puncturable top seal is positioned and set into avial adapter 31 1 , as discussed earlier with reference to Fig 2. In this way, gravity is used to hold the drug or biologic toward the top seal for easier extraction. It will be understood that other constructions of the vial infusion housing 303 may position the vial in other orientations. It will also be understood that the vial could also be positioned un-inverted. In such a case, the vent tube would then be short, and the extraction tube would be at the bottom of the vial. The vial could also be placed on its side or at an angle according to application specific needs.

[0080] The vial infusion housing 303 also securely holds a syringe 301. In one example, syringe 301 is a standard off the shelf medical syringe. It will be understood that other types of syringes and custom syringes may be used. As illustrated with reference to Fig. 2, the vial infuser housing 303 also has a syringe adapter 102 / 202 for receiving and securely holding the base portion 152 of the syringe 101 / 201 to the vial infusion housing 303. The syringe 301 has a movable plunger rod 153 that moves a plunger seal 155 up and down in its reservoir portion 151, which enables positive and negative pressures to be generated at a base 152 of the syringe 301. The base 152 of the syringe 101 / 201 is set firmly in the syringe adapter 102 / 202 of the vial infusion housing 303. In operation, when the plunger rod 153 / 253 of the syringe 301 is being withdrawn from the reservoir portion 151 (moved upwardly) in Fig. 3 A), it creates a low pressure at the base 152 inlet to the syringe 301, thereby acting to pull the drug or biologic into the reservoir 151 of the syringe 301. When the plunger rod 153 of the syringe 301 is being pushed into the reservoir portion 151 (moved downwardly in Fig. 3 A), it creates a higher pressure at the base 152 inlet of the syringe 301, thereby acting to push the drug or biologic toward the infusion set 330.

[0081] As best seen in Figs. 1 and 2, the standard medical syringe 101 / 202 has a top 154 / 254, which is often referred to as a thumb press. The thumb press 154 / 254. has a diameter approximately the same as the diameter of the reservoir portion / 251. As a result, the size of the syringe thumb press 154 / 254 acts to limit the amount of force a patient or health care worker can generate to pull a liquid from a vial into the syringe reservoir and to deliver that liquid as an injection. Although this may be acceptable for certain viscosities and volumes, it may be advantageous to provide more leverage to the patient or health care worker to ease the extraction of the drug or biologic from the vial, as well as to ease delivering the drug or biologic to the infuser 331 of infuser set 330. This not only allows for a wider range of drug volumes and biologic viscosities, but enables an easier, steadier and more consistent draw and push for the syringe 301. Accordingly, the syringe 301 of the biologic / drug delivery system 300 has a syringecarriage 307 with an enlarged ergonomic top handle 355. It will be understood that the syringe carriage 307 may be made in a wide variety of shapes and sizes. The syringe carriage 307 is securely coupled to the top of the plunger rod for syringe 301, with the carriage 307 constructed to move vertically in tracks integral to the vial infusion housing 303. In this way, when a patient or healthcare worker moves the syringe carriage 307 upwardly, then likewise the plunger rod for syringe 301 moves upwardly, creating a negative pressure at the base of the syringe 301. In a similar manner, when a patient or healthcare worker pushes the syringe carriage 307 downwardly using handle 355, then the plunger rod in syringe 301 likewise is moved downwardly, creating a positive pressure at the base of the syringe 301. This ergonomic syringe carriage 307 and handle 355 gives the patient and health care worker substantial control over the movement and positioning of the plunger seal 155 in the syringe 301.

[0082] The biologic / drug delivery system 300 also has an infusion set 330 that includes an infuser 331. The infuser 331 has a base portion 343 that has a bottom 341, which can have an adhesive patch 342. Movable carriage 344 is concentrically positioned around base 343 and is constructed to travel up and down the base 343 relative to the bottom 341. More particularly, the carriage 344 may be temporarily locked in a first position where it is fully positioned away from base 341. In this position, the needle within the infuser 331 is fully enclosed such that any patient or health care worker is not exposed to the needle. In use, the protective covering for the adhesive patch 342 is removed, and the bottom 341 of the base 343 is secured to the infusion site for the patient. As the infuser 331 is still locked in its first position, the needle is fully protected.

[0083] A flexible tubing 327 fluidly couples the infuser 331 to the vial infusion housing 303. When the patient is ready to begin the treatment, either the patient of the health care worker presses down on the cap 345 of the infuser 331, which acts to move the carriage 344 downward on the base 343 and cause the needle to be positioned subcutaneously in the patient at the infusion site. It will be understood that several alternatives are available for insertion of a cannula needle into a patient infusion site.

[0084] The biologic / drug delivery system described herein offers substantial advantages and enhancements over known devices and processes for subcutaneous injection. For example, the disclosed biologic / drug delivery system enables the following advantages:• Simple and intuitive to use, such that a patient can successfully and confidently selfadminister the drug or biologic in their home.• The inclusion of an optional air evacuation assembly means that priming is not required to eliminate air from the system, and at the end of delivery a column of air can be used to push the last of the drug or biologic through the fluid path, without the risk of infusing harmful levels of air into the patient, minimizing hold-up and overfill volumes.• Minimal steps are required to use the system, and the steps are easy and intuitive for the user to follow.• The status of the system is apparent since the patient or health care worker can monitor the drug level in the vial, and watch as the fluid enters and leaves the syringe.• The patient or health care worker knows the needle is inserted when the infuser is in the down position, but the needle is not seen by the patient to help reduce needle phobia, and the lock-out feature after use helps prevent re-use and accidental needle sticks.• The biologic / drug delivery system can be optimized for fast or slow delivery and for the force required to operate the syringe by varying parameters such tubing, needle, and syringe sizes. This allows the biologic / drug delivery system to be used with drugs having a wide range of volume and viscosity. Also, the patient or health care worker can pump at a rate that is comfortable to operate and minimizes pain at the infusion site.• The simplicity of the design makes it robust, reliable, and low in cost to manufacture.• The biologic / drug delivery system may be used for subcutaneous or intramuscular delivery.• The pharmaceutical company provides the biologic / drug in a vial primary container and does not have to invest in complex and expensive equipment to assemble the primary container with the delivery device, reducing cost, development time, and risk.• It is possible that the biologic / drug delivery system can be developed and approved by health authorities separately from the drug and can be used to deliver drugs as a noncombination product as an alternative to other available options such as a syringe and needle. This greatly reduces the development time and cost for pharmaceutical companies and provides a home-administration option for companies that may not have access to other solutions due to exclusivity agreements. Even if developed as a combination product, cost, time, and risk to develop will be significantly reduced compared to complex systems such as patch pumps.• The pharmaceutical company can quickly and easily conduct early clinical trials with the biologic / drug delivery system, then bridge to a patch pump or other subcutaneous delivery device later on if desired, since the delivery approach is similar.

[0085] Referring now to Fig. 4, a biologic / drug delivery system 400 is illustrated. Biologic / drug delivery system 400 is similar to biologic / drug delivery systems 100, 200, and 300 previously described. Accordingly biologic / drug delivery system 400 will not be described in detail. Fig. 4 shows a series of steps of the biologic / drug delivery system 400 in use.

[0086] In arrangement 410, the vial 405 is being received into the vial adapter 411. As illustrated, the vial adapter 411 has spikes and other structures to pierce the seal in the top of the vial 405, thereby enabling the extraction of a drug or biologic, and the passage of air to equalize pressure. At this point, the syringe carriage 407 is still in its down position, and the infuser 430 has not yet been adhered to the patient’s infusion site. In some embodiments tube 427 may be permanently attached between the infusion set 430 and the vial infusion housing 403, and in other cases it may be pre-connected or may need to be connected as part of the setup process. At this point the vial 405 is loaded with one full dose of a drug or biologic for the patient.

[0087] Arrangement 415 shows that the vial 405 is fully secured into the vial infusion base 403, and that the patient or health care worker moves the infuser 430 towards the patient's infusion site (represented by cylinder 451). The infuser 431 still has the backing attached to adhesive patch 442, which now needs to be removed to enable adhesion to the patient's skin. The syringe carriage 407 is still in its lower position, and the carriage 444 of the infuser 431 is in its extended position such that the needle is fully protected.

[0088] Arrangement 420 shows that the infuser 431 is adhesively secured to the skin at the patient’s infusion site. The patient or the health care worker now presses the carriage 444 of the infuser 431 downwardly, overcoming the temporary lock and causing the needle to be set subcutaneously into the patient’s skin at the infusion site. The infuser 431 now sets its carriage 444 into its insertion position. The syringe carriage 407 is still in its downward position, and no drug or biologic has been moved out of the vial 405.

[0089] Arrangements 425 and 426 show that the patient or healthcare worker now begin moving the syringe carriage 407 up and down. The first upward motion of syringe carriage 407 begins pulling a portion of drug or biologic from vial 405 toward the syringe’s reservoir. This movement eliminates any air between the vial and the syringe and allow the drug or biologic to begin collecting in the syringe’s reservoir. As the syringe carriage 407 is then pushed downward,the drug or biologic is moved into and through the tubing 427. This tubing, which initially is filled with air, begins to fill with drug or biologic. The air in the tube 427 is moved toward the infuser 431. The infuser 431 has an air evacuation assembly inside that is positioned near the input to the needle. It is desirable to position the air evacuation assembly as close to the needle as practical to minimize dead space that can hold air. This air evacuation assembly allows air from tube 427 to be exhausted harmlessly to the environment and restricts any meaningful passage of air through the needle and into the patient.

[0090] As the patient or health care worker continues to move the syringe carriage 407 up and down, the fluid or biologic fully fills the tube 427 and the drug or biologic reaches the air evacuation assembly near the needle input. At this point the air evacuation assembly stops venting air to the environment and directs the drug or biologic into the needle. In this way, the biologic / drug delivery system is fully self-priming with no meaningful risk of injecting unacceptable levels of air into the patient-Further, if there is an occasional air bubble that is trapped in the drug / biologic fluid, it will also be vented-

[0091] The patient or healthcare worker now continues to move the plunger up and down to move the drug or biologic from the vial 405 toward the infuser 431. In this way, the patient or healthcare worker can monitor the level of the drug in the vial and monitor the progress of the drug or biologic delivery. As the healthcare worker or patient continue moving the plunger, eventually the vial will become empty, and the syringe will begin pushing air into tube 427. This air pushes drug / biologic remaining in the system through to the patient. The healthcare worker or patient will be able to visually see where the fluid or biologic is within this tubing. The air evacuation unit within the infuser 431 continues to permit the drug or biologic to flow through the needle and into the patient without risk of injecting air into the patient. As soon as the air in the tubing reaches the air evacuation assembly, then the air vent for the air evacuation assembly begins venting the air harmlessly to the environment. At this point the patient or health care worker can stop moving the plunger of the syringe. With the air evacuation assembly, little drug is wasted (only the small amount in the system between the air evacuation system and the needle tip) and the full dose of the drug or biologic can be delivered effectively and efficiently from the vial 405 to the input of the needle within the infuser 431.

[0092] Now that the full dose of the drug has been delivered, the patient or health care worker lifts the carriage 444 of the infuser 431 as shown in arrangement 428, which acts to retract the needle from the patient. The carriage 444 locks in its upward position, thereby safely protectingthe needle from further human contact and preventing re-use of the device. Now, the patient or health care worker can simply peel the infuser 431 off the patient's skin as shown in arrangement 429, and the entire biologic / drug delivery system may be disposed of.

[0093] Referring now to Fig. 5, a process 500 for using a biologic / drug delivery system is described. Process 500 may use a biologic / drug delivery system as generally described with reference to biological delivery systems 100, 200, 300, and 400. Accordingly, the structures of these devices will not be described in detail.

[0094] Block 501 shows that process 500 begins with inserting a vial containing a biologic into the vial adapter of the biological delivery system. It will be understood that this vial may contain a large volume of a drug or biologic, or a volume of a more highly viscous drug or biologic. It will be understood that this process can be readily adapted to various kinds of drugs and biologies where it is desired to do a subcutaneous injection.

[0095] Block 503 shows that the biologic / drug delivery system has an infuser that is adhered to the infusion site of a patient. It will be understood there may be other ways to secure an infusion set to a patient.

[0096] Block 507 shows that once the infuser is secured to the patient's skin, then a patient or healthcare worker presses down on the cap of the infuser, which acts to insert the cannula subcutaneously into the patient at the infusion site. In some instances, this may be done in one user motion.

[0097] Block 512 shows that now the healthcare worker or patient can retract and depress the plunger rod of the syringe pump to transfer some of the drug or biologic liquid from the vial into the syringe reservoir. Each retraction of the plunger acts to extract drug from the vial and move it into the syringe, and each depression of the plunger moves air or drug from the syringe toward the infuser. As indicated at block 513, this process is self-priming, that is, the infuser has an air evacuation assembly that automatically exhausts air in the system to the environment. In this way nothing is injected into the patient until the drug or biologic is presented to the input of the needle.

[0098] Block 514 shows that the patient or health care worker continues to retract and depress the plunger rod to send a portion of the drug or biologic toward the infuser until the drug or biologic is consumed. As shown in block 519 retracting and depressing the plunger rod continues moving the drug and biologic into the needle until air begins to be exhausted from an air evacuation assembly near the input to the needle. At that point, the air evacuation assembly stopsinjecting the drug or biologic into the patient and safely exhausts any air that is generated after the drug or biologic has been fully delivered. At this point the subcutaneous injection is completed, with little to no hold up or overfill of drug needed or wasted.

[0099] As shown in block 522, the patient or healthcare worker now lifts up on the carriage of the infuser to retract the needle from the patient into the infuser body, and the infuser locks the needle into this safety position. The patient or health care worker can now peel the infuser from the patient’s skin and dispose of the biologic / drug delivery system as shown in block 526. An indicator on the infuser shows that the infuser has been used and is locked out. In some cases, steps 522 and 526 may be done as one step.

[0100] VIAL ADAPTER

[0101] The vial adapter has been generally described with reference to Figs. 1-4. More particularly, the vial adapter provides a robust mechanical connection between the vial infusion housing and the vial itself, as well as providing a fluid communication pathway between the vial contents and the biologic / drug delivery system’s fluid pathway. As glass vials are incompressible, the fluid that is removed from the vial must be replaced with something else to avoid forming a vacuum inside the vial, which is most commonly environmental air. Vented vial adapters allow air to enter the vial to prevent negative pressurization. Vented vial adapters can create issues with foaming of the drug or biologic if the air passes through the drug or biologic during the venting process, which can result in an unacceptable amount of air bubbles in the fluid path, and an excessive holdup of dmg or biologic inside the vial. The novel biologic / drug delivery system has several embodiments for a vented vial adapter that addresses the issue of drug foaming.

[0102] Dual Lumen Spike. Referring now to Fig. 6, a vial adapter assembly 600 is illustrated. Vial adapter 600 has a base vial adapter 611, a fluid tube 662, hydrophobic membrane 663 and a tube connector 664. It will be appreciated that more or fewer parts may be used. The vial adapter 611 has a dual lumen spike 660 that can pierce the seal on the vial 605, which enables the extraction of drug or biologic from the vial 605, and the inlet of air to equalize pressure. One lumen of dual lumen spike 660 provides air entry into the vial 605 (pressure equalization) while the other lumen enables drug or biologic extraction. In operation, the fluid out port 669 is fluidly connected to the syringe (not shown). When the syringe plunger is retracted, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 605 and into the syringe. The solid arrows in Fig. 6 generally show the path of the drug or biologic, while thedashed lines represent environmental air flow into the vial 605. The negative pressure in the vial 605 may cause air to be pulled from the environment, through the hydrophobic membrane 663, and into the vial 605, thereby equalizing pressure. The drug or biologic does not leak out the air passage, even under normal pressures, as the membrane 663 is hydrophobic and rejects liquids. It will be understood that although a dual lumen spike structure is used in this embodiment that two separate spaced-apart spikes each with a single lumen may be used.

[0103] Pressure Relief Valve. Referring now to Fig. 7, a vial adapter assembly 700 is illustrated. Vial adapter 700 has a base vial adapter 711, a fluid outlet 769, a hydrophobic membrane 763 and check valve 764. It will be appreciated that more or fewer parts may be used. The vial adapter 711 has a dual lumen 760 that can pierce the seal on the vial 705, which enables the extraction of drug or biologic from the vial with one lumen, and the inlet of air to equalize air pressure with the second lumen. In operation, the fluid out port 769 is fluidly connected to the syringe (not shown). When the syringe plunger is retracted, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 705. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. Extracting the drug or biologic from the vial 705 creates a negative pressure in the vial 705 as compared to the environment. When the negative pressure reaches the cracking pressure of the check valve 764, environmental air is pulled through the hydrophobic membrane 763, through the check valve 764 and into the vial 705, thereby equalizing pressure. Check valve 764 regulates the inlet of air so only larger volumes of air are introduced at once, resulting in larger bubbles which reduces foaming in the drug or biologic. The drug or biologic does not leak out the air passage, even under normal pressures, as the membrane is hydrophobic and rejects liquids, and the check valve 764 acts to further seal the air passage. It will be understood that although a dual lumen structure is used in this embodiment that two separate spaced-apart spikes each with a single lumen may be used.

[0104] Expandable Pouch. Referring now to Fig. 8, a vial adapter assembly 800 is illustrated. Vial adapter 800 has a base vial adapter 811, a fluid outlet 869, an expandable air pouch 863, and check valve 864. It will be appreciated that more or fewer parts may be used. For example, check valve 864 may be optional. The vial adapter 811 has a dual lumen 860 that can pierce the seal on the vial 805, which enables the extraction of drug or biologic from the vial 805 with one lumen, and the injection of air to equalize air pressure with the second lumen. The vial adapter 811 has a dual lumen spike 860. One lumen provides air entry into an expandable air pouch 863 that ispositioned inside the vial (pressure equalization) while the other enables drug extraction. In operation, the fluid out port 869 is fluidly connected to the syringe. When the syringe plunger is retracted, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 805. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. Extracting the drug or biologic from the vial 805 creates a negative pressure in the vial as compared to the environment. When the negative pressure reaches the cracking pressure of the check valve, environmental air may be pulled through the check valve 864 and into the expandable pouch 863. The addition of air into the pouch (even though it is held encased in the air pouch 863) causes it to expand and acts to equalize the pressure for the vial as compared to the environment. The drug or biologic does not leak out the air passage, even under normal pressures, as the air passage is sealed by the expandable air pouch 863 and the check valve 864 acts to further seal the air passage. An advantage of expandable pouch is that no foaming will occur as the air remains in the pouch, and never contacts the drug or biologic. It will be understood that although a dual lumen structure is used in this embodiment that two separate spaced-apart spikes each with a single lumen may be used.

[0105] Dual Needle. Referring now to Fig. 9, a vial adapter assembly 900 is illustrated. Vial adapter 900 has a base vial adapter 911, a fluid outlet 969, a hydrophobic membrane 963 and a safety collar or carriage 937. It will be appreciated that more or fewer parts may be used. The vial adapter 911 has a dual needle arrangement 960 that can pierce the seal on the vial 905, which enables the extraction of drug or biologic from the vial, and the passage of air to equalize pressure inside the vial. One long lumen from dual needle spike 960 provides air entry into the head space of the vial (pressure equalization) while the other enables drug extraction from a lower position. By bleeding air into the headspace above the liquid drug / biologic, the formation of bubbles and foaming is avoided. In operation, the fluid out port 969 is fluidly connected to the syringe. When the syringe plunger is pulled out, it creates a negative pressure at the syringe that draws the drug or biologic from the vial 905. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. The negative pressure in the vial 905 may cause environmental air to be pulled through the hydrophobic membrane 963, and into the vial 905, thereby equalizing pressure. The drug or biologic does not leak out the air passage, even under normal pressures, as the membrane is hydrophobic and rejects liquids.

[0106] Since the air passage needle is so long, it has a retractable safety collar 937 to reduce the chance that a human could injure themselves on an exposed needle. Prior to the vial 905 being loaded in the vial adapter 911, the safety collar 937 is positioned above the top of the air passage needle. As the vial 905 is pressed into place, it acts to retract the safety collar 937 to the bottom of the vial adapter 911. In this way the air passage needle can then extend into the head space of the vial 905.

[0107] Single Needle Dual Lumen. Referring now to Fig. 10, a vial adapter assembly 1000 is illustrated. Vial adapter 1000 has a base vial adapter 1011, a fluid outlet 1069, a hydrophobic membrane 1063 and a safety collar 1064. It will be appreciated that more or fewer parts may be used. The vial adapter 1011 has a single needle having a dual lumen arrangement 1060 that can pierce the seal on the vial 1005, which enables the extraction of drug or biologic from the vial, and the injection of air to equalize air pressure. One long lumen provides air entry into the head space of the vial (pressure equalization) while the other enables drug extraction from a lower position. By bleeding air into the headspace, the formation of bubbles and foaming is largely avoided. In operation, the fluid out port 1069 is fluidly connected to the syringe. When the syringe plunger is retracted, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 1005. Extracting the drug or biologic from the vial 1005 creates a negative pressure in the vial 1005 as compared to the environment. When the syringe plunger is retracted, it creates a negative pressure at the syringe that draws the drug or biologic from the vial 1005. The negative pressure in the vial 1005 may cause environmental air to be pulled through the hydrophobic membrane 1063, and into the vial 1005, thereby equalizing pressure. The drug or biologic does not leak out the air passage, even under normal pressures, as the membrane is hydrophobic and rejects liquids.

[0108] Since the air passage needle is so long, it has a retractable safety collar 1064 to reduce the chance that a human could injure themselves on an exposed needle. Prior to the vial 1005 being loaded in the vial adapter 1011, the safety collar 1064 is positioned above the top of the air passage needle. As the vial 1005 is pressed into place, it acts to retract the safety collar 1064 to the bottom of the vial adapter 1011. In this way the air passage needle can then extend into the head space of the vial 1005.

[0109] Telescopic Cannula. Referring now to Fig. 11, a vial adapter assembly 1100 is illustrated having a dual lumen arrangement 1160. Vial adapter 1100 has a base vial adapter 1111, a sharp hollow spike 1167, an air lumen 1165 holding a telescopic tube 1168, a fluid-outlumen 1166, a hydrophobic membrane 1 163 and a fluid out port 1 169. The hollow spike 1167 and the telescopic tube 1168 comprise a two-part cannula. It will be appreciated that more or fewer parts may be used. The vial adapter 1111 has a dual lumen spike 1167 that can pierce the seal on the vial 1105, with the first lumen 1165 forming a two part cannula and second lumen lumen 1166. The two-part cannula 1165 allows for the insert of a telescopic tube 1168 for carrying equalizing air. It will be understood that two spaced apart lumens could be used instead of a single dual lumen. The dual lumen 1160 can extract the drug or biologic from the vial 1105 through the fluid-out lumen 1166, and inject equalizing air into the vial 1105 though the tube 1168 of the two-part cannula 1165. After the vial 1105 becomes set into the vial adapter 1111, the telescopic tube 1168 extends through spike 1167 and into the vial 1105 until the tube 1168 reaches the headspace of the vial 1105. Prior to use, the telescopic tube 1168 can sit in the vial adapter 1111 without extending into areas it could be damaged. As the vial 1105 is inserted into the vial adapter 1111, the spike 1167 pieces the septum, and the tube 1168 is extended to reach into the headspace of the vial 1105. The telescopic tube 1168 is sealed to the hollow spike 1167. For example, a sliding seal or a face seal may be used, but one skilled in the art will recognize other structures to seal the flexible tube 1168 to the hollow spike 1167. In use, bubbles and foaming in the drug or biologic are substantially eliminated as the equalization air enters the headspace with little to no contact with the biologic or drug.

[0110] In operation, the fluid out lumen 1166 is fluidly connected to the fluid out port 1169, which is fluidly connected to the syringe. When the syringe plunger is pulled out, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 1105 through output port 1169. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. The negative pressure in the vial 1105 may cause environmental air to be pulled through the hydrophobic membrane 1163, through the telescopic tube 1168, and into the headspace of the vial 1105, thereby equalizing pressure. The drug or biologic does not leak out the air passage 1163, even under normal pressures, as the membrane 1163 is hydrophobic and rejects liquids.

[0111] Bubble ick Referring now to Fig. 12, a vial adapter assembly 1200 is illustrated having a dual lumen 1260 arrangement. Vial adapter 1200 has a base vial adapter 1211, a hollow spike 1267, an air wick 1268, a fluid-out lumen 1266, a hydrophobic membrane 1263 and a fluid out port 1269. It will be appreciated that more or fewer parts may be used. The vial adapter 1211 has a dual lumen 1260 that can pierce the seal on the vial 1205 using spike 1267, which enablesthe extraction of drug or biologic from the vial, and the injection of air into vial 1205 to equalize air pressure. The dual lumen 1260 has spike 1267 that can pierce the seal on the vial 1205, with the first lumen 1265 holding a wick 1268, and a second fluid-out lumen 1266. An air wick 1268 can extend through the lumen 1265 such that the wick 1268 is set in the air-inlet path. In this way, as air is pulled into the vial, bubbles form on the wick 1268 and cause the wick 1268 to rise in the drug or biologic. This wicking action encourages bubbles to cling to the wick 1268. As such, bubbles and foaming are substantially reduced. In one example, the air wick is constructed of PTFE or silicone, although it will be understood that other materials can be used.

[0112] In operation, the fluid out lumen 1266 is fluidly connected to the fluid out port 1269, which is fluidly connected to the syringe. When the syringe plunger is pulled out, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 1205 through output port 1269. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. The negative pressure in the vial 1205 may cause environmental air to be pulled through the hydrophobic membrane 1263, and into the vial 1205, thereby equalizing pressure. The drug or biologic does not leak out the air passage, even under normal pressures, as the membrane is hydrophobic and rejects liquids. It will be understood that although a dual lumen spike structure is used in this embodiment that two separate spaced-apart spikes each with a single lumen may be used.

[0113] Sidewall Accumulator . Referring now to Fig. 13, a vial adapter assembly 1300 is illustrated. Vial adapter 1300 has a base vial adapter 1311, a curved air needle 1368, hydrophobic membrane and a fluid-out port. It will be appreciated that more or fewer parts may be used. The vial adapter 1311 has a spike (not shown) that can pierce the seal on the vial 1305, which enables the extraction of drug or biologic from the vial, and the injection of air to equalize air pressure. The vial adapter 1311 has two spaced apart lumens. One lumen 1368 provides air entry into the vial (pressure equalization) while the other lumen (not shown) enables drug extraction. The lumen 1368 is curved toward the vial 1305 side wall. In operation, the bubbles cling to the lumen 1368 and travel up the sidewall 1371 of the vial 1305. As such, bubbles and foaming are substantially reduced. In operation, the fluid-out port is fluidly connected to the syringe. When the syringe plunger is pulled out, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 1305. The negative pressure in the vial 1305 may cause environmental air to be pulled through a hydrophobic membrane or check valve and into the vial 1305, thereby equalizing pressure. The drug or biologic does not leak out the airpassage, even under normal pressures, as the membrane or check valve effectively seal the air passage from fluid flow.

[0114] Snorkel Vial Septum. Referring now to Fig. 14, a vial adapter assembly 1400 is illustrated. Vial adapter 1400 has a base vial adapter 1411 and a fluid outlet 1469. It will be appreciated that more or fewer parts may be used. The vial adapter 1411 has a dual lumen arrangement 1460 that can pierce the seal on the vial 1405, which enables the extraction of drug or biologic from the vial, and the injection of air to equalize air pressure. The vial has been customized to include a long air inlet tube 1468 inside the vial 1405 that is sufficiently long that when the vial 1405 is inverted, the tip of the air inlet tube 1468 is in the headspace of the vial 1405. By bleeding air into the headspace, the formation of bubbles and foaming is largely avoided. In operation, the fluid out port 1469 is fluidly connected to the syringe. When the syringe plunger is retracted, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 1405. Extracting the drug or biologic from the vial creates a negative pressure in the vial 1405 as compared to the environment. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. The negative pressure in the vial 1405 may cause environmental air to be pulled through the long air inlet tube 1468 and into the headspace of vial 1405, thereby equalizing pressure. In this way, bubbling and foaming is substantially reduced.

[0115] Vent Conduit. Referring now to Fig. 15, a vial adapter assembly 1500 is illustrated. Vial adapter 1500 has a base vial adapter 1511, a hollow spike 1567, an extendable vent tube 1568, an air lumen 1565, a hollow fluid-out lumen 1566 and a fluid-out port 1569. The hollow spike 1567 and the extendable vent tube 1568 comprise air lumen 1565, which acts as a two-part cannula. It will be appreciated that more or fewer parts may be used. The dual lumen arrangement 1560 has a spike 1567 that can pierce the septum on the vial 1505. The extendable tube 1568 is initially retracted into a case 1571 prior to the vial 1505 being loaded. Once the vial 1505 is in place, a spring 1570 action in the case 1571 deploys the vent tubing 1568 through the lumen 1565 and into the vial 1505. Preferably the end of the vent tube 1568 extends into the headspace of the vial 1505 ensuring any air that enters the vial 1501 does not bubble through the liquid drug or biologic. The extendable tube 1568 is sealed to the hollow spike 1567. For example, a sliding seal or a face seal may be used, but one skilled in the art will recognize other structures to seal the flexible tube 1568 to the hollow spike 1567. As such, bubbles and foamingare substantially eliminated. Deployment of the vent conduit 1568 can be manual or automated. It may rely on an applied force or a pressure differential for deployment.

[0116] In operation, the fluid out lumen 1566 is fluidly connected to the fluid out port 1569, which is fluidly connected to the syringe. When the syringe plunger is pulled out, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 1505 through output port 1569. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. The negative pressure in the vial 1505 may cause environmental air to be pulled through the extendable vent tube 1568, and into the headspace of vial 1505, thereby equalizing pressure without the generation of undue bubbles or foam. It will be understood that although two separate spaced-apart lumens are shown, a dual lumen spike structure may be used

[0117] Carriage Adapter. Referring now to Fig. 16, a vial adapter assembly 1600 is illustrated. Vial adapter 1600 has a base vial adapter 1611, a carriage 1671, a hollow short spike 1667, a long vent tube 1668, a hollow fluid-out spike 1666, and a fluid out port 1669. The hollow short spike 1667 and the long vent tube 1668 comprise a two-part cannula 1660. It will be appreciated that more or fewer parts may be used. The vial adapter 1611 has hollow short spike 1667 that can pierce the septum on the vial 1605. The long vent tube 1668 is inserted though the hollow short spike 1667 until it reaches the headspace of the vial 1605. The vial adapter may comprise a travelling carriage 1671 that is activated by the user upon insertion of the vial 1605. As the user pushes the vial 1605 and carriage 1671 downward, the short spike 1167 first pierces the septum of the vial 1605. As the carriage 1671 continues to travel downward, the vent tube 1668 extends through the short spike 1667 until the seal of the vial 1605 reaches the hollow fluid-out spike. As the user continues to depress the vial and carriage, the hollow fluid-out spike pieces the seal. Finally, when the vial and carriage are fully down, the long vent tube is fully extended into the vial. In this position, the long vent tube 1668 reaches into the headspace of the vial 1605. The extendable tube 1668 is sealed to the hollow spike 1667. For example, a sliding seal or a face seal may be used, but one skilled in the art will recognize other structures to seal the flexible tube 1668 to the hollow spike 1667. As described earlier, with the tube 1668 extending into the head space, bubbles and foaming are substantially reduced.

[0118] In operation, the hollow fluid out spike 1666 is fluidly connected to the fluid out port 1669, which is fluidly connected to the syringe. When the syringe plunger is pulled out, it creates a negative pressure at the base of the syringe that draws the drug or biologic from the vial 1605through the output port 1669. The solid arrows generally show the path of the drug or biologic, while the dashed lines represent environmental air flow. The negative pressure in the vial 1605 may cause environmental air to be pulled through the vent tube 1668, and into the headspace of vial 1605, thereby equalizing pressure. It will be understood that a hydrophobic membrane may cover the air vent to assure that the drug or biologic does not leak from the air vent.

[0119] Referring now to Fig. 17, a pump system 1700 is illustrated for a biologic / drug delivery system. Generally, the pump system 1700 consists of a standard syringe 1701 that acts as an intermediary reservoir between the vial 1705 and infuser (previously described). The pump system 1700 has a handle 1755 that attaches onto the top 1754 of the syringe plunger rod 1753, which is often referred to as a thumb press. This facilitates easier and more reliable drug extraction and delivery. In Fig. 17, the left illustration shows the pump system 1700 with its syringe plunger rod 1753 in its fully down position, while the right illustration shows the pump system 1700 with its syringe plunger rod 1753 in its fully retracted position. The pump system 1700 has a vial pump housing 1703 for holding a vial adapter 1711, which has been described in detail in previous sections. The vial adapter 1711 securely holds a standard medicinal vial that contains a drug or biologic for subcutaneous injection. It will be appreciated that vial 1705 may also be custom designed for application specific needs, for example to work with various sized vials. The vial infusion housing 1703 also holds a pump syringe system 1775. The pump syringe system 1775 has a fluidics subassembly 1706 as previously described that has a syringe adapter 1702 for receiving a base 1752 from a syringe 1701. The fluidics subassembly 1706 has been previously described. The pump syringe system 1775 has a syringe 1701 that has a plunger rod 1753 that is slidably received into a syringe reservoir 1751. A syringe seal (plunger)1771 is at the distal end of plunger rod 1753 for maintaining a fluidic seal within the syringe reservoir 1751. The syringe 1701 may be a standard medical syringe, or in some cases may be a custom design to meet application specific needs.

[0120] The pump syringe system 1775 also has a syringe carriage 1707 that is constructed to be movable up and down relative to a carriage base 1708, which is securely coupled to the vial infusion housing 1703. The syringe 1701 has a plunger rod 1753 that has a top 1754 which is secured to the handle 1755. In the illustrated example the thumb press of the syringe 1754 simply clips into a cooperating mating piece in the handle 1755. It will be understood that other structures may be used to secure the top 1754 (thumb press) of the syringe plunger rod 1753 to the handle 1755. In this way, upward and downward movements of the syringe carriage 1707immediately and precisely translate to upward and downward movements of the syringe plunger rod 1753 that sits within the syringe reservoir 1751.

[0121] In one embodiment, the handle 1755 is constructed to be at least double the diameter of the plunger rod thumb press 1754 and is constructed with a thicker and more ergonomic design. It will be understood that many diameters, shapes, materials, and sizes may be used for this ergonomic handle 1755. Using such an ergonomic handle 1755, a patient or health care worker is able to more comfortably and securely hold the handle 1755 as compared to the relatively small and fragile plunger thumb press 1754. The additional size and shape of the handle 1755 enables the patient or health care worker to obtain leverage in withdrawing the drug or biologic from the vial 1705 and in delivering the drug or biologic from the syringe reservoir 1751 to the infuser. This additional leverage generated by using the handle 1775 enables the patient or healthcare worker to more easily, consistently, and comfortably complete a successful subcutaneous injection that delivers the full treatment to the patient.

[0122] Referring now to Fig. 18, an alternative pump 1800 is illustrated. A compressible bladder 1801 can provide an alternative to the syringe-based infuser system described with reference to Fig. 17. In pump 1800, the bladder 1801 generally acts as the temporary reservoir for receiving the drug or biologic from the vial 1805, and then applying a pressure to deliver the drug or biologic to the infuser (not shown). The user depresses the bladder 1801 using a lever 1875, which acts to push air or the drug or biologic out of the bladder and down the fluid path toward the infuser. Upon release, the bladder 1801 expands back to its neutral position, drawing in drug or biologic from the vial 1805. Bladder 1801 extracts drug or biologic as it rises due to material elasticity or connection to the lever 1875. The patient or health care worker continues this pattern of compressing the handle to deliver drug or biologic, and releasing the handle to withdraw drug or biologic from the vial 1805 until the full therapeutic dose has been subcutaneously delivered. The bladder 1801 can be depressed directly by the user, or there may optionally be a lever 1875 or similar mechanism to aid in bladder compression. It will be understood that the bladder 1801 can be made of different flexible materials and in various sizes and shapes. The fluidics subsystem design and operation is similar in pump 1800 as compared to the fluidics subsystem previously described so will not be described in detail.

[0123] Referring now to Fig. 19, an alternative pump 1900 is illustrated. A flexible balloon 1901 can provide an alternative to the syringe-based infuser system described with reference to Fig. 17. In pump 1900, a flexible balloon 1901 and plastic tube 1902 cooperate to generally actas the temporary reservoir for receiving the drug or biologic from the vial 1905, and then applying a pressure to deliver the drug or biologic to the infusion set (not shown). The user squeezes the flexible balloon 1901 using his or her hand, which acts to push air or the drug or biologic out of the ballon 1901 and tube 1902 and down the fluid path toward the infuser. Upon release, the flexible balloon 1901 expands back to its neutral position, drawing in drug or biologic into the tube 1902 from the vial 1905. The patient or health care worker continues this pattern of squeezing the balloon 1901 to deliver drug or biologic, and releasing the balloon 1901 to withdraw drug or biologic from the vial 1905 until the full therapeutic dose has been subcutaneously delivered. It will be understood that the balloon 1901 can be made of different flexible materials and in various sizes and shapes.

[0124] The flexible balloon 1901 operates in conjunction with the clear plastic tube 1902 to act as a reservoir and pump, in a manner similar to a traditional pipette. When the user squeezes the balloon 1901, air is pushed down the infusion tubing to the infuser set. Upon release, the balloon 1901 sucks a limited amount of liquid drug / biologic up into the rigid reservoir tube 1902. The liquid drug or biologic never fills the reservoir tube 1902 more than the fixed volume of the balloon, so there is no risk of drug or biologic holdup inside the balloon. The fluidics subsystem design 1906 and operation is similar in pump 1900 as compared to the fluidics subsystem previously described so will not be described in detail.

[0125] Referring now to Fig. 20, a pump system 2000 is illustrated for a biologic / drug delivery system. Generally, the pump system 2000 consists of a standard syringe 2001 that acts as an intermediary reservoir between the vial 2005 and infuser (previously described). The pump system 2000 has a handle 2055 that attaches onto the thumb press 2054 of the syringe plunger rod 2053, facilitating easier and more reliable drug extraction and delivery. The plunger rod 2053 has a plunger 2055 at its distal end for sealing to the syringe walls, thereby enabling positive and negative pressures to be generated as the plunger rod 2053 is moved. The illustration in Fig. 20 shows the pump system 2000 with its syringe 2001 in its fully retracted position.

[0126] The pump system 2000 also has a pump syringe system 2075. The pump syringe system 2075 has a syringe carriage 2007 that is constructed to be movable up and down relative to a carriage base 2008, which is securely coupled to the vial infusion housing 2003. As the handle 2055 is securely coupled to the thumb press 2054 of the syringe 2053, upward and downward movements of the syringe carriage 2007 immediately and precisely translate toupward and downward movements of the syringe plunger 2053 that sits within the syringe reservoir 2051.

[0127] The pump syringe system 2075 also has a fluidics subassembly 2006 that has a syringe adapter 2002 for receiving a base 2052 from a syringe 2001. The syringe 2001 may be a standard medical syringe, or in some cases may be a custom design to meet application specific needs. The fluidics subsystem 2006 generally acts to assure that (1) when the syringe system 2075 is being withdrawn that the drug or biologic is withdrawn only from the vial 2005, and none is pulled back from the infusion tube and (2) when the syringe system 2075 is being depressed that the drug and biologic is delivered only to the infusion tubes, and none is pushed back toward the vial 2005. The fluidics subsystem is described in more detail with reference to Figs. 21-24.

[0128] Referring now to Fig. 21A, a component 2100 of the biologic / drug delivery system is illustrated. It will be understood that although component 2100 is illustrated as a single sub assembly, the functionality of component 2100 may be accomplished by the interconnection of discrete parts. Component 2100 is a fluidics subsystem 2106. The fluidics assembly acts as a junction between the vial, syringe and infusion set. The fluidics subsystem 2106 has a top piece 2106a that mates with a bottom piece 2106b. As illustrated, top piece 2106a and bottom piece 2106b are intended to slot or snap together. It will be understood that these top and bottom pieces may be glued, screwed, welded, or otherwise connected. The top piece 2106a has a syringe port 2102 constructed to receive the base of a standard syringe. It will be understood that the syringe port 2102 may be modified to accept a custom syringe connection according to the specific manual or powered pump that is used. The bottom piece 2106b has an input port 2131 for receiving the drug or biologic fluid from a vial. The bottom piece 2106b also has an output port 2132 for connection to an infusion set. It will be understood that these connections may be made through permanent or temporary connections. For example, the connections may be Luer or other connectors, or alternatively permanent connections can be made.

[0129] The fluidic subsystem 2106 also has a pair of check valves. Check valves in the fluidics subassembly prevent fluid backflow. Check valves used can include umbrella valves, duckbill valves and any other valve that prevents fluid backflow. It will be understood that the type, style, material, and construction of the check valves may be selected according to the specific drug or biologic that is being delivered. Check valve 2109 is received into the bottom piece 2106b in slot 2110. In a similar manner check valve 2125 is received into bottom piece 2106b in slot 2126. Fig 2 IB illustrates a top view of the fluidics sub assembly 2106 after it is fully assembled. It will beunderstood that two or more check valves can be used in series for redundancy in the event one of the valves fails, for example from a particle that becomes lodged in the valve.

[0130] Referring now to Fig. 22, a diagram 2200 of the fluidics subassembly 2206 is shown. A first view 2201 shows the fluidics sub assembly 2206 operating in the condition when the syringe plunger is being retracted in the syringe reservoir while the base of the syringe is secured in the syringe port 2202. As illustrated, the dotted lines show that the plunger of the syringe is being withdrawn, which acts to create a lower pressure within the syringe reservoir and at the syringe port 2202. Check valve 2209 is selected and configured to open in such a low pressure situation, while check valve 2225 is selected and configured to close. As a result, the drug or biologic in the vial connected to input port 2231 is able to follow the arrow path through check valve 2209, through the syringe port 2202, and into the syringe reservoir. Importantly, no drug, biologic, or air is permitted to pass through check valve 2225 in this low-pressure situation.

[0131] A second view 2202 shows the fluidics sub assembly 2206 operating in the condition when the syringe plunger is being inserted in the syringe reservoir while the base of the syringe is secured in the syringe port 2202. As illustrated, the dotted lines show that the plunger of the syringe is being moved into the syringe, which acts to create a higher pressure within the syringe reservoir and at the syringe port 2202. Check valve 2225 is selected and configured to open in such a high-pressure situation, while check valve 2209 is selected and configured to close. As a result, the drug or biologic in the syringe connected to syringe port 2202 is able to follow the arrow path through check valve 2225, through the output port 2232, and into infuser. Importantly, no drug, biologic, or air is permitted to pass through check valve 2209 in this high- pressure situation.

[0132] Referring now to Fig. 23, a fluidic subassembly 2300 is illustrated. Fluidic subassembly 2306 is similar to the fluidic subassemblies described with reference to Fig. 21A / B and Fig. 22, and so will not be described in detail. Fluidic subassembly 2306 is a subassembly for a biologic / drug delivery system, such as biologic / drug delivery systems 100, 200 and 300, which were described with reference to Figs. 1, 2 and 3. Fluidics subassembly 2306 has a syringe port 2302 for securely receiving a base portion of a standard medical syringe. It will be understood that syringe port 2302 could be modified to adapt to a different syringe or pump system. In operation, the syringe acts as a temporary reservoir of drug or biologic between a vial of the drug or biologic and the infusion set that injects the drug or biologic into the patient. It will be appreciated that when a syringe is connected to the syringe port 2302, the syringe will generate anegative pressure when its plunger is being retracted, a positive pressure when the plunger is being inserted, and a static pressure when the plunger is not being moved.

[0133] Fluidics subassembly 2306 has a vial input port 2331 that fluidically couples to a standard medical drug vial. Although input port 2331 is illustrated to have a removable connection, it will be understood that other removable connectors or a permanent connection may be used. Also, although a standard medical vial is used as an example, it will be understood that custom vials or drug / biologic containers may be used. A vial check valve 2109 is positioned in the fluid path between the vial input port 2331 and the syringe port 2302. This vial check valve 2309 is selected and constructed to ensure that when the syringe is generating sufficient negative pressure, fluid and air can be pulled from the vial input port 2131 toward the syringe port 2302, but if the syringe is generating a positive or ambient pressure, then no fluid or air can move through the check valve 2309 toward the vial input port 2331. Accordingly, a negative pressure at the syringe port 2302 enables a one-way fluid path 2133 from the vial input port 2331 toward the syringe port 2302.

[0134] Fluidics subassembly 2306 has an infuser output port 2332 that fluidically couples to an infusion set, such as infuser 131, 231 or 331 described with reference to Figs. 1, 2 and 3. Although output port 2332 is illustrated to have a removable connection, it will be understood that other removable connectors or a permanent connection may be used. An infusion check valve 2125 is positioned in the fluid path between the infusion output port 2332 and the syringe port 2302. This infusion check valve 2325 is selected and constructed to ensure that when the syringe is generating sufficient positive pressure, fluid and air can be moved from the syringe port 2302 toward the infusion set output port 2132, but if the syringe is generating a negative or ambient pressure, then no fluid or air can move through the check valve 2325 toward the syringe port 2302. Accordingly, a positive pressure at the syringe port 2302 enables a one-way fluid path 2134 from the syringe port 2302 toward the infusion port 2332. It will be understood that alternative types, shapes, materials, and sizes may be used for the check valves. It will also be understood that more or fewer check valves may be used, and that in some cases redundant serial or parallel check valves may be used.

[0135] Referring now to Fig. 24, a flowchart 2400 of a fluidic subassembly is illustrated. In flowchart 2400, block 2402 shows that a fluidic subassembly is provided. This fluidic subassembly has a pump port, a vial port, and an infusion set port. It will be understood that more or fewer parts may be used according to application specific needs. Block 2403 shows thatthe fluidic subassembly has a vial check valve and an infusion set check valve. It will be understood that in specific situations additional or fewer check valves may be used.

[0136] As illustrated in block 2405, the pump generates a low pressure at the pump port. As shown in block 2409, the vial check valve opens and the infusion set check valve closes. It will be understood that the order of these actions may be adjusted according to application specific needs. Then, as shown in block 2413 air, the drug, or the biologic is moved from the vial port to the pump port. As illustrated in flowchart 2400, the left side path illustrates functions as a syringe is retracted, for example. It will be understood that other types of manual pumps may be used.

[0137] As illustrated in block 2422, the pump generates a high pressure at the pump port. As shown in block 2426, the vial check valve closes and the infusion set check valve opens. It will be understood that the order of these actions may be adjusted according to application specific needs. Then as shown in block 2436, air, the drug, or the biologic is moved from the pump port to the infusion set port. As illustrated in flowchart 2400, the right side path illustrates functions as a syringe is depressed, for example. It will be understood that other types of manual or automated pumps may be used. As illustrated in flowchart 2400, the upward arrow shows that the pump may have multiple cycles of up and down motions, such as the extraction and depression of a syringe.

[0138] Referring now to Fig. 25, a biologic / drug delivery system 2500 is illustrated. Biologic / drug delivery system 2500 is similar to biologic / drug delivery systems 100, 200 and 300 previously described, therefore drug delivery system 2500 will not be described in detail. The fluidics assembly 2506 may include a flow restrictor 2507 between the pump 2575 and the infusion set 2530. This creates a pressure drop, acting as a safeguard against the user overpressurizing the infuser 2531. Use of a flow restrictor 2507 means that the user must exert a higher force on the pump 2575 in order to achieve similar pressures downstream of the flow restrictor 2507. The flow restrictor 2507 may be in the form of an orifice plate, a flow control valve, a capillary tube, a mesh screen or porous media. Two or more flow restrictors may be used in parallel to avoid clogging of the system. It will also be understood that a pressure buffer may be used, either alone or in combination with the flow restrictor. A pressure buffer is a flexible section that expands to dampen pressure spikes, then contracts again when the pressure normalizes

[0139] INFUSION SET

[0140] Referring now to Fig. 26, an infusion set system 2600 is shown. Infusion set system 2600 includes infuser 2631 with infusion tubing 2627 and a connector 2628 to connect the infusion tubing 2627 to a pump or syringe (not shown). It will be understood that tubing 2627 may be permanently attached to infuser 2631, or that tubing 2627 may be connected and disconnected to the infuser 2631 using adapters. Preferably, infusion tubing 2627 is clear, which enables the patient or health care worker to monitor drug or biologic flow within the tubing during the delivery process. The infusion set 2630 has an infuser 2631, which includes a carriage 2644 that moves vertically relative to a base 2643. The base 2643 has a bottom 2641 that includes an adhesive patch 2642 that attaches to the infusion site of a patient. Fig. 26 shows the infusion set 2630 prior to use. In this initial state, the carriage 2644 is set in its fully retracted “up” position. In this way the needle cannula is entirely safe and protected within the infuser 2631 such that the needle will not be damaged and the needle will not accidentally harm the patient or health care worker.

[0141] The infuser 2631 is the part of the biologic / drug delivery system that attaches to the patient. The infuser 2631 may house a cannula, an attachment method to the patient’s skin, a mechanical applicator and a method for permanent or removable connection of fluid communication with the rest of the biologic / drug delivery system. The infuser 2631 may provide a mechanism to allow the user to physically introduce the cannula to the infusion site. The infuser 2631 may also optionally contain an air evacuation assembly that allows air in the fluid line to escape before being delivered to the infusion site. The air assembly device has been generally described, but will be described in detail with reference to Figs. 28A-C and 29A-C. The infuser 2631 may also optionally incorporate a method for making the device needle-safe after use, such as fully retracting it back into the infuser 2631 and locking. The infuser 2631 may also optionally provide a method of communication that dose delivery is complete, for example, a transparent window in the infuser 2631. In one example, the center portion of the cap 2645 could provide a transparent window to enable the patient or health care worker to see the cannula assembly and its associated tubing that is positioned inside the housing 2631. In another example, a color change of an indicator can be made after using the device so the user can distinguish a used device from a new device and also to indicate that the needle has been retracted and locked out successfully.

[0142] Referring now to Fig. 27 A, an expanded view of an infusion set 2730 is illustrated. The infusion set 2730 is similar to the infusion set 2630 described with reference to Fig. 26, so will not be described in detail. The infusion set 2730 has a base piece 2743 having a bottom 2741. An adhesive patch 2742 is securely attached to the bottom 2741. The adhesive patch 2742 has a paper protective layer, which may be removed to expose an adhesive layer. This adhesive layer may be used to secure the infuser 2731 to the infusion site of a patient. A carriage 2744 is slideably received onto the base 2743. A lock ring 2746 is constructed to operably couple the base 2743 to the carriage 2744. More particularly, the lock ring 2746 acts to (1) retain the carriage 2744 in its retracted position before use of the infusion set 2700; (2) retain the carriage 2744 in its down position during drug delivery; and (3) once the carriage 2744 has been retracted after use, assure that the carriage cannot be depressed a second time. In operation, the carriage 2744 moves only upwardly and downwardly relative to the base 2743 so no complicated twisting motions are needed . As illustrated, several individual parts comprise the infuser 2731 from the cap 2745 to the adhesive 2742.

[0143] As generally introduced above, the lock ring 2746 may be slideably attached inside carriage 2744. In this way, lock ring 2746 holds the carriage in a first up position prior to use, in a second down position during drug delivery, and final safe third position with the carriage locked in an up position after use. The first position holds the carriage 2744 in its retracted position such that that needle is above and spaced apart from bottom 2741. In this position, the needle is fully protected inside base 2743. This first position is used prior to the infuser 2731 being applied to the patient’s infusion site. In this way, as the patient or healthcare worker are preparing the biologic / drug delivery system for use, the needle is safely positioned within base 2743 to avoid accidental injury to the patient or health care worker.

[0144] Cannula assembly 2780 is connected to the infusion tube 2727 for receiving the drug or biologic from the syringe or pump of the biologic / drug delivery system. The cannula assembly 2780 has a needle 2733 extending from its distal end. It will be understood that the needle 2733 may be a standard needle that is received into a cooperating meeting portion of the cannula assembly 2780. It will also be understood that the needle 2733 may be otherwise constructed integrally with the cannula assembly 2780. The cannula assembly 2780 is securely received into carriage 2744. In this way, the position of the assembly 2780 is determined by the position of carriage 2744 relative to base 2743. For example, when carriage 2744 is fully retracted, the cannula assembly 2780, including needle 2733, is fully retracted inside base 2743 and abovebottom 2741 . However, when the carriage 2744 is fully depressed, the cannula assembly 2780 is set in a position such that needle 2733 is set subcutaneously into the patient.

[0145] Optionally, the cannula assembly 2780 may include an air evacuation assembly 2790 that allows air in the fluid line to escape so that is not delivered into the needle 2733 and patient. The air evacuation assembly 2790 has been generally described, but will be described in detail with reference to Figs. 28A-C and 29A-C.

[0146] Referring now to Fig. 27B, isometric and simplified schematic views (2735, 2736 & 2737) of the infuser are illustrated in four views. Several components, such as cannula assembly 2780 are not shown to aid in a clearer description. View 2701 shows the infuser fully in its up position prior to use, view 2702 shows the infuser fully depressed such that the needle (not shown) is in position for subcutaneous injection, and view 2703 shows the infuser fully retracted after use. Finally, view 2738 shows the lock ring being visible to the user after needle retraction, which acts as an indicator that the infuser 2731 has been used.

[0147] Referring primarily to view 2701, carriage 2744 is shown in its initial up position. For ease of explanation, the cannula assembly 2780 is not illustrated. Cannula assembly 2780 couples to the cannula support 2757, which moves up and down with the carriage 2744. The cannula support 2757 is positioned concentrically within the carriage 2744. Carriage 2744 is initially held in an upwards position by two flexible insertion detents 2751 between lock ring 2746 and base 2743. In one embodiment the insertion detents 2751 are made from POM, but it will be understood that other materials can be used. The insertion detents 2751 engage with the base, which can be MABS or ABS. When the user applies enough force to the cap 2745 to overcome the resistance from the insertion detents 2751, the carriage 2744 travels toward the bottom of the base 2743. The lock ring 2746 is retained by the carriage 2744 such that it also travels toward the bottom of the base 2743.

[0148] Referring now to views 2702 and 2703, as the lock ring 2746 approaches the end of travel, two flexible lock ring capture clips 2752 between the lock ring 2746 and the base 2743 are deformed. In one embodiment the capture clips 2752 are made from POM, but it will be understood that other materials can be used. The capture clips 2752 engage with the base, which can be MABS or ABS. As the user moves the carriage 2744 downward, the two flexible lock ring capture clips 2752 clip into corresponding capture hooks on the side of base 2743. In this way, the lock ring 2746 is firmly attached to the base 2743, and the lock ring 2746 cannot bemoved upward. At this point, the cannula is fully inserted, and delivery of the drug / biologic can commence.

[0149] During drug delivery, the carriage 2744 is held in the downward position by two flexible retraction detents 2753 between the lock ring 2746 and the carriage 2744. In one embodiment the retention detents 2753 are made from POM, but it will be understood that other materials can be used. In this position, the needle 2733 is driven below base 2743 such that the needle is set subcutaneously in the patient at the infusion site to a specified depth, either for subcutaneous or intramuscular delivery. Since it is important that the needle be securely held during drug or biologic delivery, the lock ring 2746 firmly retains the carriage 2744 to the base with retention detents 2753 so that the needle cannula 2780 is securely held in this delivery position

[0150] When delivery is complete, the user lifts carriage 2744 relative to the base 2743, overcoming flexible retraction detents 2753. As the lock ring 2746 is firmly retained at the bottom of base 2743, the lock ring 2746 remains attached to the base, which allows the user to lift the carriage and cannula upward. A set of lockout clips 2754 is configured between the lock ring 2746 and the carriage 2744. These lockout clips 2754 were previously deformed during the downward travel of the carriage 2744. In this way, they provide a tension to internal structures in the carriage 2744. As a result, when the user moves the carriage 2744 upward to the point where the carriage 2744 reaches its fully retracted position, these lockout clips 2754 snap back into a neutral position, locking carriage 2744 in the up position. With the needle inside the base 2743, the patient or health care worker is protected from accidental contact with needle. This position also facilitates a safer and more sanitary disposal. Also, the patient never sees the needle, which helps with needle phobia.

[0151] It will be understood that there are many alternative structures, constructions, and materials that may be substituted for the infuser 2631 that are within the scope of this disclosure. Although a detailed embodiment has been described with reference to Fig. 27A and Fig. 27B, several alternative embodiments are briefly described below. As these alternative embodiments of infuser 2731 are simply modifications of descriptions made above, they will not be described in detail.

[0152] Infuser 2731 is illustrated and described as being circular in shape, and therefore the illustrated embodiment allows for the carriage 2744, base 2743, and lock ring 2746 to have a slidable concentric relationship. However, it will be understood that other shapes may be used,such as oval, rectangular, or other geometric shapes. In such alternatively shaped embodiments, the carriage 2744, base 2743, and lock ring 2746 will still have a slidable relationship, with that slidable relationship being in an upward and downward direction, with no need for a rotational motion relative to the base 2743. The lock ring 2746 may be positioned between the base 2743 and the carriage 2744, or alternatively the lock ring 2746 can be positioned inside the base 2743. One skilled in the art will appreciate other alternative structures can be used.

[0153] Infuser 2731 is illustrated and described as having insertion detents 2751 positioned to provide vertical resistance to the carriage to initially hold the carriage in a retracted position. It will be understood that these insertion detents 2751 may be flexible, rigid, or semi-rigid.Further, the insertion detents 2751 may be integrally formed into a wall, or may be set into a cooperating indent. The insertion detents 2751 may be structured as individual space-apart structures, or may form a complete or nearly complete ring. In one example the insertion detents 2751 are constructed as one or more flexible detents and are positioned between the lock ring 2746 and the base 2743. In another example, the insertion detents 2751 are constructed as one or more flexible detents and are positioned between the base 2743 and the carriage 2744. One skilled in the art will appreciate other alternative structures can be used.

[0154] Infuser 2731 is illustrated and described as having capture clips 2752, with the capture clips 2752 sized and positioned to be retained by one or more capture hooks 2747 coupled to the base 2743 such that when the carriage 2744 is fully depressed, the lock ring 2746 is retained to the base 2743. In one example the capture clips 2752 may be flexible or deformable, and in other cases the capture clips 2752 may be rigid or semi-rigid. In another example the capture hooks 2747 may be flexible, and in other cases the capture hooks 2747 may be rigid or semi rigid. Further, the capture clips 2752 or capture hooks 2747 may be integrally formed into a wall, or may be set into a cooperating indent. The capture clips 2751 or capture hooks 2747 may be structured as individual space-apart structures, or may form a complete or nearly complete ring. One skilled in the art will appreciate other alternative structures can be used.

[0155] Infuser 2731 is illustrated and described as having carriage lockout clips 2754 that are used to secure the carriage 2744 in a retracted position after use such that the infuser 2731 cannot be used a second time. In some embodiments the carriage lockout clips 2754 may be positioned between the base 2743 and the carriage 2744. In other embodiments the carriage lockout clips 2754 are positioned between the lock ring 2746 and the carriage 2744. The carriage lockout clips 2754 may be flexible or deformable, and in other cases may be rigid or semi rigid. The carriagelockout clips 2754 may be structured as individual space-apart structures, or may form a complete or nearly complete ring. In a more specific example, the carriage lockout clips 2754 are sized and positioned to be flexible and deform as the carriage travels downward to its fully depressed position, and snap back to a neutral position when the carriage 2744 travels back to its fully retracted position. One skilled in the art will appreciate other alternative structures can be used.

[0156] Infuser 2731 is illustrated and described as having retraction detents 2753, which are optional. These retraction detents 2753 are sized and positioned to hold the carriage 2744 in its fully depressed position but allow the carriage 2744 to be moved upward with application of a sufficient force by the user or health care provider. In some embodiments the retraction detents 2744 may be positioned between the lock ring 2746 and the carriage 2744, and in other embodiments the retraction detents 2753 may be positioned between the base 2743 and the carriage 2744. It will be understood that the retraction detents 2753 can be flexible, deformable, or maybe rigid or semi rigid. One skilled in the art will appreciate other alternative structures can be used.

[0157] Referring now to Fig. 27C, another advantageous embodiment 2738 is illustrated. In embodiment 2738, the base 2743 is fully or partially transparent, clear, or highly translucent plastic, and the lock ring 2746 is brightly colored, such as a red or yellow plastic. Prior to use and during use, the lock ring 2746 would not be visible to the user, as it is substantially shielded from view by the opaque carriage 2744. After use when the carriage 2744 is retracted, the lock ring 2746 remains locked in the down position and is visible through the base 2743. This acts as a safety indicator to show that the infuser 2731 has been used and must be disposed of. As a further safety mechanism, the carriage 2744 is also locked in its up and safe position. It will be understood that only a portion of the base 2743 would need to be clear, transparent or highly translucent. For example, the bottom of the base 2743 could remain opaque, with just the sidewall (or a portion) of the base 2743 being clear, transparent or highly translucent.

[0158] One embodiment constructs the base from a MABS (methyl methacrylate acrylonitrile butadiene styrene) MABS is a clear and transparent version of ABS plastic. It is known for its high clarity, impact resistance, and good mechanical strength, making it suitable for use as the base 2743 for the infuser 2731. As it is so clear, the user or healthcare provider can readily see the lock ring, if locked in its down position. It will be appreciated that other clear, transparentfor highly translucent plastic could be used. The cap 2745 and the carriage 2744 may still be made from ABS plastic or other suitable material.

[0159] In some embodiments the infuser 2731 is illustrated and described as having a fully or partially clear base 2743. Such a base 2743 enables a user or healthcare provider to visually be alerted that the lock ring 2746 has been locked to the base 2743. When the lock ring 2746 is locked to the base 2743, then the user or health care provider will know that the infuser 2631 has already been used, and so should now be disposed of. This visual indicator acts as a safety indicator to assure the infuser 2631 is not used a second time.

[0160] In some embodiments, the base 2743 may be fully clear, transparent, or highly translucent, and in other cases only a portion of the base 2743 will be clear, transparent or highly translucent. For example a band or hole in the base 2743 may be clear, transparent or highly translucent, and the rest of the base 2743 more opaque. As described, the lock ring 2746 would be positioned inside the base 2743 such that the base 2743 would obscure visual observation of the lock ring 2746 unless at least some portion of the base 2743 was clear, transparent, or highly translucent. In an alternative safety indicator, the lock ring 2746 may be outside the base 2743 and inside the carriage 2744 so a retained lockring 2746 would be visible even if the base 2743 were opaque.

[0161] CANNULA ASSEMBLY

[0162] Referring now to Fig. 28A, cannula assembly system 2800 is illustrated. Cannula assembly system 2800 generally includes a cannula assembly 2880 that has an integrally formed air evacuation assembly 2890. Generally, the cannula assembly 2880 is constructed from a top piece 2887 and a bottom piece 2888. It will be understood that top piece 2887 and bottom piece 2888 may be constructed to snap together, be glued together, or be otherwise securely coupled. When the top piece 2887 and bottom piece 2888 are coupled together, a fluid void 2889 is created. It will be understood that the size, shape, and volume of this fluid void 2889 may be set according to application specific needs, such as drug or biologic volumes and viscosities.

[0163] The bottom piece 2888 has a needle port 2883 that is constructed to receive a standard needle or cannula (not shown). It will be understood that the needle or cannula may be integrally formed into bottom piece 2888. The top piece 2887 has an infusion tube port 2881 constructed to receive the output from an infusion tube that is delivering a drug or biologic. The drug or biologic, which is moved by pressure provided from the syringe or pump of the biologic / drug delivery system, moves to input 2882 and then into void 2889. Continued pressure on the drug orbiologic moves the drug or biologic into fluid output 2886 and to the needle port 2883, where it is then injected into the patient through an attached needle.

[0164] When injecting a drug or biologic into a patient, it is critical that large volumes of air not be injected into the patient. For that reason, the cannula assembly 2880 as described thus far without an air evacuation assembly would require priming the needle prior to insertion. That is, the drug or biologic would need to be pumped into the cannula assembly 2880 to evacuate the air from the tubing and spaces within the cannula assembly 2880. Only after the drug or biologic has reached the needle, or when substantially all the air has been evacuated from the cannula assembly 2880, can the needle be set into the patient and delivery initiated. Further, at the completion of the drug delivery, care must be taken not to drive air into the patient after all of the drug or biologic has been delivered subcutaneously. In this way, the patient or health care worker must carefully monitor the vial or infusion tubing to visually track when the drug or biologic has been used. For example, the patient or healthcare worker could monitor the tubing to see where the air is in the tubing and then stop prior to the air making it to the cannula assembly 2880. This puts a significant burden on the patient or health care worker to maintain a safe delivery. Further, excess drug or biologic must be provided in the vial to account for the need to retain some drug or biologic within the tubing or the biologic / drug delivery system. This amount of drug or biologic is often referred to as “overfill” and can represent a significant cost as many of these drugs and biologies are very expensive. The undesirable effects of priming, delivery of air at the completion of the infusion, and overfill may be avoided by including an air evacuation assembly in cannula assembly 2880, discussed immediately below.

[0165] Air Evacuation Assembly. As illustrated in Fig. 28A, the air evacuation assembly 2890 consists of three components that cooperate with other parts of the cannula assembly 2880. First, top piece 2887 has an air vent 2874. This air vent 2874 is intended to exhaust air from the biologic / drug delivery system at three important times: (1) at initial setup to exhaust the air from the infusion tube as the drug / biologic is moved toward the needle; (2) to exhaust any air bubbles that happen to be trapped in the drug / biologic during delivery; and (3) to exhaust any air delivered to the cannula assembly 2880 after the drug or biologic delivery is completed. By doing so, the air evacuation assembly 2890 enables the cannula assembly 2880 to require no priming, and to safely use all the drug or biologic without significant overfill or fear of harming the patient.

[0166] The second component of the air evacuation assembly 2890 is a hydrophobic vent membrane 2873. Hydrophobic membranes are well known to allow the passage of air, while restricting the passage of a liquid, especially one based upon water. It will be understood that the particular hydrophobic vent 2873 may be selected according to the specific drug or biologic used. The third component of the air evacuation assembly 2890 is a hydrophilic membrane 2885. Hydrophilic membranes are well known to enable the passage of fluids, such as drugs or biologies, while restricting the passage of air (after wetting). It will be understood that the specific hydrophilic filter 2885 would be selected according to the specific drug or biologic used, as well as the required back pressure to assure all air is vented through air vent 2874. It will also be understood that needle passage 2891 may be sized to partially restrict the flow of air, the drug or the biologic.

[0167] For initial use, as the drug or biologic is first being moved into the cannula assembly 2880 air would be pushed into the void 2889 under pressure from the pump and syringe of the biologic / drug delivery system. The hydrophobic membrane 2873 is selected to have a relatively low back pressure to air flow. More particularly, that pressure is selected to be lower than the back pressure to air flow of the hydrophilic membrane and the needle passage 2891. As a result, the void 2889 has a lower pressure passage from the inlet 2882 to the air vent 2874 as compared to the inlet 2882 to the needle port 2883. As a result, the air would be directed through the hydrophobic vent 2883 and exhausted to the environment through air vent 2884. As the void 2889 fills with drug or biologic, the hydrophilic membrane 2885 would become wetted and permit the passage of the drug or biologic into the fluid out 2886 and to the needle port 2887. However, the drug or biologic would not be permitted to pass through the hydrophobic vent membrane 2883, so little or none of the drug or biologic would exit air vent 2884. When drug delivery is complete, the void 2889 would again begin filling with air. This air would vent through the hydrophobic vent membrane 2873 and air vent 2874, and again would be restricted from passing into the fluid out port 2886 by the hydrophilic membrane 2885, which is now wetted and would further restrict the passage of air.

[0168] Fig. 28B shows the air evacuation assembly 2890 in operation when air is being received into the void 2889. As illustrated by the arrow path, air is received through infusion port 2881, passes into input port 2882 and is received into void 2889. As discussed with reference to Fig. 28A, a relatively low-pressure air pathway extends between the input port 2882 to the air vent 8774 as compared to the input port 2882 and the needle port 2883. As a result, when the airpressure is raised in the void 2889 to overcome the backpressure of the hydrophobic membrane 2883 the air will follow the lower pressure pathway and exhaust through the air vent 2874. As a result, the air safely passes through the hydrophobic vent membrane 2883, through vent 2884 and safely into the environment, and only a minimum amount of air is passed through the needle port 2883 as described more fully below. Fig. 28B thereby shows how the air evacuation assembly operates when the void 2889 contains air.

[0169] Fig. 28C shows the air evacuation assembly 2890 in operation when the drug or biologic is being received into the void 2889. As illustrated by the arrow path, the drug or biologic is received through infusion port 2881, passes into input port 2882 and is received into void 2889. The drug or biologic is restricted by the hydrophobic membrane 2873 and so cannot pass into air vent 2874. Instead, pressure is raised in the void 2889 until drug or biologic pressure overcomes the backpressure of the hydrophilic membrane 2885 and the needle passage 2891. Once the hydrophilic membrane is wetted, and the backpressure of the hydrophobic membrane is overcome, then only the drug or biologic can flow into the output port 2886 and into the needle port 2887 and into the patient. Fig. 28C thereby shows how the air evacuation assembly 2890 allows only drug or biologic to be injected to the patient, and not air. It will be understood that the fluid out port 2886, the needle port 2887, and the void in the needle will all be initially filled with air, which is a very small amount of air, and that this air may be safely injected on initial use. This amount of injected air could be adjusted by appropriately selecting the porosity of the hydrophilic (2885) and hydrophobic (2873) membranes and selecting the size and shape of the fluid out port 2886 and the needle passage 2891 and needle port 2887.

[0170] As illustrated in Fig. 29A, an alternate air evacuation assembly 2990 uses a check valve 2985 instead of a hydrophilic membrane to allow drug or biologic to pass from the infusion tube input 2981 into the needle port 2883 while restricting air. The alternative air evacuation assembly generally comprises three components that cooperate with other parts of the cannula assembly 2980. First, top piece 2987 has an air vent 2984. This air vent 2984 is intended to exhaust air from the biologic / drug delivery system at three important times: (1) at initial setup to exhaust the air from the infusion tube port 2981 and the fluid as the drug and biologic is moved toward the needle; (2) during drug delivery to remove air bubbles that have been trapped in the drug; and (3) at the end of drug delivery to exhaust any air delivered to the cannula assembly 2980 after the drug or biologic delivery is completed. By doing so, the air evacuation assembly2990 enables the cannula assembly 2980 to require no priming, and to safely use all the drug or biologic without overfill or fear of harming the patient.

[0171] The second component of the air evacuation assembly 2890 may be a check valve 2985. Check valves are well known to allow the passage of fluid once a cracking pressure has been exceeded, while restricting the passage of both air and fluid below the cracking pressure. It will be understood that the particular check valve 2985 may be selected according to the specific drug or biologic used. In use, the check valve 2985 cooperates with a housing portion 2996 to maintain a fluid and air seal between void 2989 to chamber 2992 as long as the pressure difference between the void 2989 and the chamber 2992 remains below the check valve 2985 cracking pressure. The third component of the air evacuation assembly 2890 may be a flow restrictor 2995. The flow restrictor 2995 is set between the top piece 2987 and the bottom piece 2988. The size of the opening in the flow restrictor 2995 is set according to the viscosity of the drug or biologic, the porosity of the hydrophobic membrane 2983, the anticipated pressure from the pump or syringe, and the cracking pressure of the check valve. A narrowing in cross sectional area of the fluid path results in an increase in fluid velocity (continuity equation). In accordance with Bernoulli’s principle, the increase in fluid velocity causes a drop in pressure. On top of this, the flow restrictor introduces frictional losses and energy losses due to turbulent flow, requiring higher kinetic energy from the user to achieve a given pressure in the system.

[0172] As previously described, a low-pressure air pathway is enabled between the input port 2981 and the air vent 2984. By doing so, any significant quantity of air presented into void 2989 will pass to the air vent 2984, and will be restricted from moving into the lower chamber 2992 or the needle port 2987. There are three components that may be selected to assure that the low- pressure air pathway is enabled. Each of these components are in the drug or biologic path, and act to increase the pressure needed to move the drug or biologic from the void 2998 to the lower chamber 2992. First, as described above, a check valve 2985 may be used. Second, as described with reference to Fig. 28, a hydrophilic membrane may be used. Third, a flow restrictor, as described above, may be used. It will be understood that these three components may be used alone or in any combination to achieve the required pressure for the particular drug or biologic to be injected. Further, as previously described, redundant serial check valves may be used to assure proper operation in the event a particle in the drug or biologic jams the check valve into a constant open position.

[0173] For initial use, as the drug or biologic is first being moved into the cannula assembly 2980, air is pushed into the void 2989 and upper chamber 2991 under pressure from the pump and syringe of the biologic / drug delivery system, but is not able to pass through the check valve 2985, as the air pressure is below the check valve 2985 cracking pressure. More particularly, the components are selected to have a lower pressure air pathway from the input port 2981 to the vent 2984, as compared to the air pathway from the input port 2981 to the lower chamber 2992. As a result, the air is directed through the hydrophobic membrane 2983 and exhausted to the environment through air vent 2984. As the void 2989 and upper chamber 2991 fill with drug or biologic, the drug or biologic is not permitted to pass through the hydrophobic vent membrane 2983, so the pressure would build in the upper chamber 2991. Once the pressure from the drug or biologic exceeds the cracking pressure of the check valve 2985, the check valve 2985 flanges would be pushed away from the housing 2996 and permit the drug or biologic to flow into the lower chamber 2992, and into the needle cannula 2933.

[0174] When drug delivery is nearly complete, the void 2989 would again begin filling with air. This air would vent through the hydrophobic vent membrane 2983 and air vent 2984. Based on the size of the optional flow restrictor 2995, the void would empty sufficiently for air to begin venting from vent 2984. The patient or health care worker would know to stop the pump or syringe action as soon as air began venting. Alternatively, the patient or health care worker could be instructed to watch for the vial to be completely empty, and then continue to give a set number of additional plunges. The number of pumps would be set to ensure that all (or at least substantially all) of the drug / biologic in the vial is injected into the patient, with very little waste.

[0175] Fig. 29B shows the air evacuation assembly 2900 in operation when air is being received into the void 2989. As illustrated by the arrow path, air is received through infusion port 2981 and is received into void 2989. The air is restricted by the flow restrictor 2995 and the check valve 2985 and so cannot pass into lower chamber 2992. Instead, air pressure is raised in the void 2989 until the air pressure in void 2989 overcomes the backpressure of the hydrophobic membrane 2983 (which is less than the cracking pressure of the check valve). Once the air pressure is above the hydrophobic backpressure, the air safely passes through the hydrophobic vent membrane 2983, through vent 2984 and safely into the environment. Fig. 28B thereby shows how the air evacuation assembly operates when the void 2989 contains air.

[0176] Fig. 29C shows the air evacuation assembly 2990 in operation when the drug or biologic is being received into the void 2989. As illustrated by the arrow path, the drug orbiologic is received through infusion port 2981 and is received into void 2989. The drug or biologic is restricted by the hydrophobic membrane 2983 and so cannot pass into air vent 2984. Instead, the pressure is raised in the void 2989 until drug or biologic pressure moves the drug or biologic through the flow restrictor 2995 and into the upper chamber 2991 Pressure continues to mount in the upper chamber 2991 until the cracking pressure of the check valve 2985 is exceed. Once the cracking pressure is exceeded, the drug or biologic pushes between the flanges of the check valve 2985 and the gasket 2996, which allows the drug or biologic to flow into the lower chamber 2992 and out the needle port 2987 and into the needle 2933 and patient. Fig. 29C thereby shows how the air evacuation assembly 2990 allows only drug or biologic to be injected into the patient, and not air. It will be understood that the lower chamber 2992, the needle port 2987, and the void in the needle will all be initially filled with air, which is a very small amount of air, and that this air may be safely injected on initial use. This amount of injected air could be adjusted by selecting the size and shape of the the lower chamber 2992, and the needle port 2987.

[0177] Referring now to Fig. 30, a flowchart 3000 shows how the cannula assembly is safely self-priming. Flowchart 3000 shows in block 3002 that initially, prior to any fluid drug or fluid biologic being delivered to the patient, air is received through the infusion tubing and is directed into an air chamber in a cannula assembly. The cannula assembly has an air vent which has a hydrophobic membrane. The air chamber also has a needle port that connects to the insertion needle, which has an associated hydrophilic membrane and / or check valve and / or a flow restrictor. It will be understood that in some cases the check valve may be supplemented or replaced by a hydrophilic membrane. As shown in block 3005, and as discussed earlier, the cannula assembly is designed and has components selected to create a lower air pressure path from the infusion tubing input to the air exhaust, as compared to the air pressure required to pass air into the needle port. As a result, as shown in block 3010, the air initially received into the cannula assembly will exhaust through the lower air pressure pathway through the air vent.

[0178] As shown in block 3012, the infusion tubing will begin delivering a fluid drug or fluid biologic into a chamber in the cannula assembly. The fluid drug or fluid biologic is not able to pass through the hydrophobic membrane to the air vent. As a result, the fluid pressure builds in the chamber as shown in block 3017 and once sufficiently high, the fluid drug or biologic will pass from the chamber to the needle port. More particularly, the fluid drug or biologic will pass into the needle port once the pressure in the chamber exceeds both the back pressure of thehydrophilic membrane and the cracking pressure of the check valve, if present. As shown in block 3019, the cannula assembly has been primed (air exhausted) so that the drug or biologic may be injected into the patient, and yet substantially no air is injected into the patient.

[0179] Referring now to Fig. 31, a flowchart 3100 shows how the cannula assembly substantially reduces the amount of expensive and wasteful overfill. As shown in block 3102 the fluid drug or fluid biologic is received from the infusion tubing and passed into a chamber of the cannula assembly. Block 3104 shows that the fluid drug or fluid biologic from the chamber is delivered to the needle port of the cannula assembly. Then, that fluid drug or fluid biologic is injected into the patient at an infusion site as shown in block 3107. It will be appreciated that this injection may be either subcutaneous or intramuscular. As shown in block 3111, at some point the drug vial becomes empty and air begins entering into the infusion tube that is connected to the cannula assembly. Often, this tubing is transparent so that the patient or the caregiver can see that air has now entered the tubing. As illustrated in black 315, the patient or caregiver can continue pumping air into the infusion tubing until air is received into the chamber of the cannula assembly. In this way, the cannula assembly substantially reduces the amount of expensive and wasteful overfill.

[0180] Any air received into the chamber at this point will have a lower pressure path to the air vent as compared to the needle port. As a result any air received into the chamber toward the end of the injection will be exhausted from the chamber through the air vent, as shown in block 3119. As shown in block 3124, once sufficient air has been received into the chamber, there will be insufficient pressure to push the fluid drug or the fluid biologic into the needle port. At this point the injection of the fluid drug or the fluid biologic will stop. More particularly, the flow of the drug or biologic will stop as the pressure at the hydrophobic vent is lower than the pressure is at the hydrophilic filter or the flow restrictor. Further, the fluid pressure at the hydrophobic vent is lower than the cracking pressure of the check valve, if present. As shown in block 3128, air received into the chamber through the infusion tubing will continue to be vented through the air vent until the syringe or pump stops.

[0181] Referring now to Fig. 32, an alternative embodiment for the drug delivery system 3200 is illustrated. Drug delivery system 3200 has a fluidics subsystem 3203 that receives a syringe pump 3201 and a vial adapter 3211. Vial adapter 3211 is sized and constructed to receive a vial 3205 of a drug or biologic. Drug delivery system 3200 enables the delivery of a drug or biologic,without the drug or biologic ever being in contact with the syringe pump 3201 . Tn some situations, it may be advantageous to have the drug or biologic moved from the vial 3205, through the infusion tubing 3227 and to the infusion set 3230, without direct contact to the syringe pump 3201.

[0182] In operation, a patient or healthcare provider would retract the plunger rod 3253 from the syringe pump 3201. This will create a negative pressure at the syringe adapter 3252. This negative pressure will cause check valve 3221 to open such that air may be pulled into the syringe pump 3201 from the air inlet 3220. It will be understood that fdters and other preconditioning structures may be used. This negative pressure at the syringe adapter 3252 also keeps the check valve 3222 closed. In this way no fluid is pulled from the vial 3205 toward the syringe 3201. Once the syringe has sufficient air in it, the user would stop retracting the plunger rod 3253, which would cause check valve 3221 to close.

[0183] The patient or health care provider then begins depressing the plunger rod 3253, which creates a positive air pressure at the syringe adapter 3252. Check valve 3221 is closed and the positive pressure causes check valve 3222 to open such that air may flow toward the vial adapter 3211. Check valve 3223 also opens under this positive pressure and allows air to flow into the vial 3205. This injected air goes to the top of the vial 3205, and once sufficient pressure has been reached, the air will begin pushing the drug or biologic out of the vial 3205 through check valve 3224. This check valve 3224 is optional, but may be useful to provide redundancy. The drug or biologic would then be moved out of the fluidic subsystem 3203 to the infusion tubing 3227 and finally to the infuser, which are part of the infusion set 3230. Once the plunger rod 3253 has been fully depressed, the positive pressure decreases, which closes check valve 3222, check valve 3223, and check valve 3224.

[0184] It will be understood that more or fewer check valves may be used, and that different specific placements may be used to support application needs. It will also be appreciated that the syringe pump 3201 may use alternative pumps, such as those described earlier.

[0185] An alternative embodiment will now be described with reference to Fig. 32. For the alternative embodiment, the syringe pump 3201 is replaced by a pressure generating device that is capable of generating a pressure on a gas, such as air or nitrogen. In some cases this may be a constant pressure. In one example, a pressurized vessel or canister of gas may be used, or a powered peristaltic pump may be used. Generally, the pressure generating device will have a pressure regulator to maintain the gas pressure at a safe level to assure proper operation of thedrug delivery system 3200. It will be understood that the fluid may be either a gas or a liquid. For example, a liquid can be used, or a liquid containing hyaluronidase. The liquid could be, for example, a water based solution. It will be understood that other liquids may be used depending on the specific therapeutic agent to be injected.

[0186] When using a pressure generating device 3201 in the drug delivery system 3200, the need for check valves is reduced or even eliminated. For example, the air vent 3220 and all the check valves could be removed, thereby providing a direct fluid path from the pressure generating device 3201 to the vial 3205, and a direct path from the vial 3205 to the infusion tubing 3227. In one example, the check valve 3252 could be replaced with a valve or some other pressure regulator. It will be understood that check valves may be used in the pressurized gas / liquid path, or in the therapeutic agent path. Further, a flow restrictor could be used in the therapeutic agent path to further control or limit the pressure the therapeutic agent applies to the infusion set.

[0187] While particular preferred and alternative embodiments of the present intention have been disclosed, it will be appreciated that many various modifications and extensions of the above-described technology may be implemented using the teaching of this invention. All such modifications and extensions are intended to be included within the true spirit and scope of the appended claims.

Claims

CLAIMSWhat is claimed is:

1. A medical device for injecting a volume of a therapeutic agent into an injection site of a patient, comprising: a vial adapter for retaining a vial of the therapeutic agent; a pump for generating a positive pressure and a negative pressure, the pump having a reservoir for holding at least a portion of the volume of the therapeutic agent; an infusion set having infusion tubing connected to an infuser, the infuser having a cannula assembly with a needle or cannula sized for injecting the therapeutic agent to the injection site; and a fluidics subassembly operably connecting the vial adapter, the pump and the infusion set, further comprising: a vial check valve in a vial fluid path between the vial adapter and the pump that is constructed (1) to enable fluid flow in the vial fluid path toward the reservoir when the pump is generating the negative pressure and (2) to restrict flow from the reservoir toward the vial adapter when the pump is generating the positive pressure or at an ambient pressure; and an infusion check valve in an infusion fluid path between the pump and the infusion set that is constructed (1) to enable fluid flow from the pump toward the infusion set when the pump is generating the positive pressure and (2) to restrict flow from the infusion set toward the pump when the pump is generating the negative pressure or at an ambient pressure; and wherein the infusion set further comprises an air evacuation assembly which further comprises a vented fluid chamber for venting air that is received into the chamber from the infusion tubing.

2. The medical device of 1, wherein the pump is a manual pump or a manual syringe pump.

3. The medical device of 1, wherein the pump is a powered pump or a powered syringe pump.

4. The medical device of 1, wherein the therapeutic agent is a biologic.

5. The medical device of 4, wherein the biologic is injected in a volume 5 ml or greater.

6. The medical device of 4, wherein the biologic has a viscosity of greater than 10 cP.

7. The medical device of 1, wherein the therapeutic agent is a chemical drug.

8. The medical device of 7, wherein the chemical drug is injected in a volume of 5 ml or greater.

9. The medical device of 7, wherein the chemical drug has a viscosity of greater than 10 cP.

10. The medical device of 1, wherein the air evacuation assembly is in the cannula assembly such that the vented fluid chamber is positioned close to an input to the needle.1 1 . The medical device of 1 , wherein the vial is a standard medical vial.

12. The medical device of 1, wherein the needle or cannula is sized for a subcutaneous injection.

13. The medical device of 1, wherein the needle or cannula is sized for an intramuscular injection.

14. The medical device of 1, wherein the fluid flow is a flow of the therapeutic agent or a flow of air.

15. The medical device of 1, wherein there is a plurality of vial check valves or a plurality of infusion check valves.

16. The medical device of 1, wherein the components are pre-assembled, the end user only having to attach a vial of the therapeutic agent to the vial adapter.

17. The medical device of claim 1, further comprising: one or more pressure restrictors between the pump and the air evacuation assembly, the pressure restrictors being constructed to restrict the pressure of fluid flowing from the pump to the cannula assembly; and wherein the one or more pressure restrictors is selected from the group of check valves, hydrophilic membranes, flow restrictors, fdters and pressure buffers.

18. A cannula assembly for a medical device that injects a volume of a therapeutic agent into an injection site of a patient, comprising: an infusion tube port constructed to connect to infusion tubing that carries air or the therapeutic agent;a needle port for attaching a needle or cannula that is used to inject the therapeutic agent into the patient; a chamber between the infusion tube port and the needle port that receives the air or the therapeutic agent from the infusion tube port; an air vent from the chamber; a hydrophobic vent membrane between the chamber and the air vent, the hydrophobic vent membrane selected to exhaust pressurized air from the chamber and to restrict the therapeutic agent from passing into the air vent.

19. The cannula assembly according to claim 18, wherein the cannula assembly is selfpriming, such that (1) air received into the chamber is exhausted until the chamber is substantially filled with the therapeutic agent and (2) the therapeutic agent is not under sufficient pressure to move through the needle port until that chamber is substantially filled with therapeutic agent.

20. The cannula assembly according to claim 18, wherein the cannula assembly substantially eliminates the need for significant therapeutic agent overfill, such that (1) when delivery of the therapeutic agent is nearly complete, air enters the chamber from the infusion tube port; (2) reduced pressure in the chamber stops delivery of the therapeutic agent through the needle port; and (3) the air entering the chamber safely vents through the air vent.

21. The cannula assembly according to claim 18, wherein during therapeutic agent delivery, the cannula assembly safely vents air bubbles present in the therapeutic agent such that (1) air bubbles in the chamber can pass through the hydrophobic membrane and the air vent; (2) pressure in the chamber remains sufficiently high to not substantially interrupt the flow of therapeutic agent through the needle port.

22. The cannula assembly of claim 18, further comprising a check valve between the chamber and the needle port, the check valve being constructed to restrict the flow of air from the chamber into the needle port while the chamber is filling with the therapeutic agent; and wherein when the chamber is substantially filled with the therapeutic agent, pressure on the therapeutic agent in the chamber increases until the check valve reaches its cracking pressure, which enables the therapeutic agent to flow from the chamber toward the needle port.

23. The cannula assembly of claim 18, further comprising:a hydrophilic membrane between the chamber and the needle port, the hydrophilic membrane being constructed to restrict the flow of air from the chamber into the needle port while the chamber is filling with the therapeutic agent.

24. The cannula assembly of claim 18, further comprising: a flow restrictor between the chamber and the needle port, the flow restrictor being constructed to restrict the flow of air from the chamber into the needle port while the chamber is filling with the therapeutic agent.

25. A medical device for injecting a volume of a biologic into an injection site of a patient, comprising: a vial adapter for holding a vial of the biologic; a manual syringe pump for generating a positive pressure and a negative pressure, the manual syringe pump having a reservoir for holding at least a portion of the volume of the biologic; an infusion set having infusion tubing connected to an infuser, the infuser having a cannula assembly with a needle sized for injecting the biologic to the injection site; and a fluidics subassembly operably connecting the vial adapter, the manual syringe pump and the infusion set, further comprising: a vial check valve in a vial fluid path between the vial adapter and the manual syringe pump that is constructed (1) to enable fluid flow in the vial fluid path toward the reservoir when the pump is generating the negative pressure and (2) to restrict flow from the reservoir toward the vial adapter when the pump is generating the positive pressure or at an ambient pressure; and an infusion check valve in a infusion fluid path between the manual syringe pump and the infusion set that is constructed (1) to enable fluid flow from the manual syringe pump toward the infusion set when the manual syringe pump is generating the positive pressure and (2) to restrict flow from the infusion set toward the manual syringe pump when the manual syringe pump is generating the negative pressure or at an ambient pressure; and wherein the cannula assembly further comprises an air evacuation assembly, which further comprises: an infusion tube port constructed to connect to infusion tubing that carries air or the biologic;a needle port for attaching a needle or cannula that is used to inject the biologic into the patient; a chamber between the infusion tube port and the needle port that receives the air or the biologic from the infusion tube port; and an air vent from the chamber.

26. The medical device of 25, wherein the biologic is injected in a volume 5 ml or greater.

27. The medical device of 25, wherein the biologic has a viscosity of greater than 10 cP.

28. The medical device of 25, wherein the needle or cannula is sized for a subcutaneous injection.

29. The medical device of 25, wherein the needle or cannula is sized for an intramuscular injection.

30. The medical device of 25, wherein the fluid flow is a flow of the biologic or a flow of air.

31. The medical device of 25, wherein there is a plurality of vial check valves or a plurality of infusion check valves.

32. The medical device of 25, further comprising a hydrophobic vent membrane between the chamber and the air vent, the hydrophobic vent membrane selected to exhaust pressurized air from the chamber and to restrict the biologic from passing into the air vent.

33. The medical device of 25, wherein the cannula assembly is self-priming, such that (1) air received into the chamber is exhausted until the chamber is substantially fdled with the biologic and (2) the biologic is not under sufficient pressure to move through the needle port until that chamber is substantially filled.

34. The medical device of 25, wherein the cannula assembly substantially eliminates the need for biologic overfill, such that (1) when delivery of the biologic is nearly complete, air enters the chamber from the infusion tube port; (2) reduced pressure in the chamber stops delivery of the biologic through the needle port; and (3) the air entering the chamber safely vents through the air vent.

35. The medical device of 25, wherein during biologic delivery, the cannula assembly safely vents air bubbles present in the biologic such that (1) air bubbles in the chamber pass through theair vent; (2) pressure in the chamber remains sufficiently high to not substantially interrupt the flow of biologic through the needle port.

36. The medical device of claim 1, further comprising: one or more pressure restrictors between the manual syringe pump and the air evacuation assembly, the pressure restrictors being constructed to restrict the pressure of fluid flowing from the manual syringe pump to the cannula assembly; and wherein the one or more pressure restrictors is selected from the group of: check valves, hydrophilic membranes, flow restrictors, filters and pressure buffers.

37. A method for restricting the injection of harmful amounts of air during the subcutaneous or intramuscular injection of a therapeutic agent, comprising: providing an infusion tube port for a cannula assembly; receiving pressurized air from the infusion port into a small chamber in the cannula assembly; creating a lower pressure air pathway from the chamber to an air vent, as compared to pressure restrictions in a pressure-restricted pathway from the chamber to a needle port; preventing the therapeutic agent from moving out the air vent; exhausting air from the chamber through the air vent when the lower pressure air pathway from the chamber to the air vent exists; and wherein the pressure restrictions are generated by one or more restrictors selected from the group of: check valves, hydrophilic membranes, flow restrictors, filters and pressure buffers.

38. The method according to claim 37, further comprising using a hydrophobic membrane to prevent the therapeutic agent from moving out the air vent.

39. The method according to claim 37, further comprising: exhausting air from the chamber through the air vent as the chamber fills with the therapeutic agent, increasing the pressure in the chamber as the chamber fills with the therapeutic agent; and moving the therapeutic agent from the chamber to the needle port when the pressure in the chamber exceeds the pressure restrictions in the pressure-restricted pathway.

40. The method according to claim 37, further comprising:moving the therapeutic agent from the chamber to the needle port as long as the pressure in the chamber exceeds the pressure restrictions in the pressure-restricted pathway; receiving air bubbles into the chamber that had been entrapped in the therapeutic agent; and exhausting air from the air bubbles from the chamber through the air vent while continuing to move the therapeutic agent to the needle port.

41. The method according to claim 37, further comprising: emptying the infusion tubing of the therapeutic agent as the injection nears completion, pumping air from the infusion port into the small chamber in the cannula assembly from the empty infusion tubing; decreasing the pressure in the chamber as the amount of the therapeutic agent is reduced in the chamber; and stopping the movement of the therapeutic agent from the chamber to the needle port when the pressure in the chamber is below the pressure restrictions in the pressure-restricted pathway.

42. The method according to claim 37, wherein the therapeutic agent is a biologic.

43. The method according to claim 42, wherein the biologic is injected in a volume greater than 5 ml.

44. The method according to claim 42, wherein the biologic has a viscosity of greater than 10 cP.

45. The method according to claim 37, wherein the therapeutic agent is a chemical drug.

46. The method according to claim 45, wherein the chemical drug is injected in a volume of 5 ml or greater.

47. The method according to claim 45, wherein the chemical drug has a viscosity of greater than 10 cP.

48. An infuser for injecting a therapeutic agent into an injection site of a patient, comprising: a carriage having an internal cannula support that is constructed to hold a cannula assembly;a base for attachment to the injection site of the patient, the base sized to be slideably received into the carriage; a lock ring slideably coupled to the base or the carriage; one or more insertion detents, the one or more insertion detents sized and positioned to provide vertical resistance to the carriage to initially hold the carriage in a retracted position; one or more capture clips coupled to the lock ring, the capture clips sized and positioned to be retained by one or more capture hooks coupled to the base, such that when the carriage is fully depressed the lock ring is retained to the base; one or more carriage lockout clips that secure the carriage in a retracted position after use; and wherein the lockout clips permanently lock the carriage when it is lifted to its fully retracted position.

49. The infuser according to claim 48, wherein the lock ring is positioned between base and the carriage.

50. The infuser according to claim 48, wherein the lock ring is positioned inside the base.

51. The infuser according to claim 48, wherein the insertion detents are flexible.

52. The infuser according to claim 48, wherein the one or more insertion detents are constructed as one or more flexible detents and are positioned between the lock ring and the base53. The infuser according to claim 48, wherein the one or more insertion detents are constructed as one or more flexible detents and are positioned between the base and the carriage.

54. The infuser according to claim 48, wherein the one or more capture clips are flexible or deformable.

55. The infuser according to claim 48, wherein the one or more capture hooks are flexible or deformable.

56. The infuser according to claim 48, wherein the one or more lockout clips are positioned between the lock ring and the carriage.

57. The infuser according to claim 48, wherein the one or more lockout clips are positioned between the base and the carriage.

58. The infuser according to claim 48, wherein the one or more lockout clips are flexible or deformable.

59. The infuser according to claim 58, wherein the one or more lockout clips are sized and positioned to be flexible and deform as the carriage travels upwards toward its fully retracted position, and snap back to a neutral position when the carriage in its fully retracted position60. The infuser according to claim 48, further including one or more retraction detents that are sized and positioned to hold the carriage in its fully depressed position but allow the carriage to be moved upward with a sufficient force;61 . The infuser according to claim 60, wherein the retraction detents are positioned between the lock ring and the carriage.

62. The infuser according to claim 60, wherein the retraction detents are positioned between the base and the carriage63 The infuser according to claim 60, wherein the retraction detents are flexible or deformable.

64. The infuser according to claim 48, wherein the base has at least a portion that is clear, transparent, or highly translucent such that the lock ring is visible when the infuser has been used and the lock ring is in the down position and the carriage is in its retracted position.

65. The infuser according to claim 64, wherein the base is fully clear, transparent, or highly translucent.

66. The infuser according to claim 64, wherein the lock ring is brightly colored or highly contrasting as compared to the color of the carriage.

67. The infuser according to claim 64, wherein the lock ring is positioned between base and the carriage.

68. The infuser according to claim 64, wherein the lock ring is positioned inside the base.

69. A vial adapter for holding a sealed vial containing a therapeutic agent, comprising: a base constructed to hold the vial; a spike having an air lumen and constructed to pierce a septum of a medical vial of a therapeutic agent;a telescopic tube constructed to extend through the air lumen and into a headspace of the therapeutic agent for receiving equalizing air pressure; a fluid-out lumen that is constructed to allow the therapeutic agent to be pulled under negative pressure from an output port of the vial, wherein removal of the therapeutic agent also generates a negative pressure in the headspace; an air vent in the base, the air vent being fluidically coupled to the telescopic tube; wherein the negative pressure in the headspace draws air through the air vent, through the telescopic tube, and into the headspace.

70. The vial adapter according to claim 69, further comprising a hydrophobic membrane covering the air vent to prevent the therapeutic agent from moving out the air vent.

71. The vial adapter according to claim 69, wherein the air lumen and the fluid-out lumen are constructed as a two-part cannula.

72. The vial adapter according to claim 71, wherein the air lumen and the fluid-out lumen are constructed as a dual lumen.

73. The vial adapter according to claim 71, wherein the air lumen and the fluid-out lumen are constructed as spaced apart lumens.

74. A vial adapter for holding a sealed vial containing a therapeutic agent, comprising: a base constructed to hold the vial; a spike having an air lumen and constructed to pierce a septum of a medical vial of a therapeutic agent; an air wick constructed to extend through the air lumen and into vial for receiving equalizing air pressure; a fluid-out lumen that is constructed to pierce the septum and allow the therapeutic agent to be pulled under negative pressure from an output port of the vial, wherein removal of the therapeutic agent also generates a negative pressure in the headspace; an air vent in the base, the air vent being fluidically coupled to the hollow spike; and wherein the negative pressure in the headspace draws air from the air vent, to the air wick, and into the vial.

75. The vial adapter according to claim 74, further comprising a hydrophobic membrane covering the air vent to prevent the therapeutic agent from moving out the air vent.

76. The vial adapter according to claim 74, wherein the air lumen and the fluid-out lumen are constructed as a dual lumen.

77. The vial adapter according to claim 74, wherein the air lumen and the fluid-out lumen are constructed as spaced-apart lumens.

78. A vial adapter for holding a sealed vial containing a therapeutic agent, comprising: a base constructed to hold the vial; a spike having an air lumen and constructed to pierce a septum of a medical vial of a therapeutic agent; an extendable vent tube constructed to extend through the air lumen and into a headspace of the therapeutic agent for receiving equalizing air pressure; a case holding a spring under tension or compression, the spring operably coupled to the extendable vent tube; a fluid-out lumen that is constructed to pierce the septum and allow the therapeutic agent to be pulled under negative pressure from the output port of the vial, wherein removal of the therapeutic agent also generates a negative pressure in the headspace; an air vent, the air vent being fluidically coupled to the extendable vent tube; and wherein when the vial is set into the base, the spring is released to propel the extendable vent tube to the headspace.

79. The vial adapter according to claim 78, further comprising a hydrophobic membrane covering the air vent to prevent the therapeutic agent from moving out the air vent.

80. The vial adapter according to claim 78, wherein the air vent is in the case.

81. The vial adapter according to claim 78, wherein the air lumen and the fluid-out lumen are constructed as a two-part cannula.

82. A vial adapter for holding a sealed vial containing a therapeutic agent, comprising: a base housing; a travelling carriage in the housing and constructed to hold the vial, the travelling carriage having a retracted position and a depressed position; a spike having an air lumen and positioned in the carriage, the air lumen constructed to pierce a septum of a medical vial of a therapeutic agent;a long hollow vent tube in the base and constructed to extend through the air lumen as the carriage moves from its retracted position toward its depressed position; a fluid-out spike having a fluid-out lumen, the spike constructed to pierce the septum and allow the therapeutic agent to be pulled under negative pressure from an output port of the vial, wherein removal of the therapeutic agent which also generates a negative pressure in the headspace; an air vent, the air vent being fluidically coupled to the long hollow vent tube; and wherein when the vial is set into the depressed position, the fluid-out spike has pierced the seal of the vial and the long hollow tube extends through the fluid-out lumen into the headspace.

83. The vial adapter according to claim 82, further comprising a hydrophobic membrane covering the air vent to prevent the therapeutic agent from moving out the air vent.

84. The vial adapter according to claim 82, wherein the fluid-out spike and the long hollow vent tube are constructed as a two-part cannula.

85. A medical device for injecting a volume of a therapeutic agent into an injection site of a patient, comprising: a vial adapter for holding a vial of the therapeutic agent; a pump for generating a positive pressure and a negative pressure, the pump having a reservoir for holding air; an infusion set having infusion tubing connected to an infuser, the infuser having a cannula assembly with a needle sized for injecting the therapeutic agent to the injection site; and a fluidics subassembly operably connecting the vial adapter, the pump and the infusion set, further comprising: one or more air vent check valves that (1) enable air flow into the pump reservoir when the pump is generating a negative pressure and (2) restrict air from moving from the reservoir to the environment when the pump is generating positive pressure; one or more pump check valves in a pump air path between the pump and the vial adapter that is constructed (1) to enable air flow from the reservoir toward the vial adapter when the pump is generating the positive pressure and (2) to restrict flow from the vial adapter toward the reservoir when the pump is generating the negative pressure; andwherein the infusion set further comprises an air evacuation assembly which further comprises a vented fluid chamber for venting air that is received into the chamber from the infusion tubing.

86. The medical device of 85, further comprising one or more infusion check valves in an infusion fluid path between the vial adapter and the infusion set that is constructed (1) to enable fluid flow from the vial adapter toward the infusion set when the pump is generating the positive pressure and (2) to restrict flow from the infusion set toward the vial adapter when the pump is generating the negative pressure.

87. The medical device of 85, wherein the pump is a manual pump or a manual syringe pump.

88. The medical device of 85, wherein the pump is a powered pump or a powered syringe pump.

89. The medical device of 85, wherein the therapeutic agent is a biologic.

90. The medical device of 89, wherein the biologic is injected in a volume 5 ml or greater.

91. The medical device of 89, wherein the biologic has a viscosity of greater than 10 cP.

92. The medical device of 85, wherein the therapeutic agent is a chemical drug.

93. The medical device of 92, wherein the chemical drug is injected in a volume of 5 ml or greater.

94. The medical device of 92, wherein the chemical drug has a viscosity of greater than 10 cP.

95. The medical device of 85, wherein the air evacuation assembly is in the cannula assembly such that the vented fluid chamber is positioned close to an input to the needle.

96. The medical device of 85, wherein the vial is a standard medical vial.

97. The medical device of 85, wherein the needle is sized for a subcutaneous injection.

98. The medical device of 85, wherein the needle is sized for an intramuscular injection.

99. The medical device of 85. wherein the components are pre-assembled, the end user only having to attach a vial of the therapeutic agent 1 to the vial adapter.

100. A medical device for injecting a volume of a therapeutic agent into an injection site of a patient, comprising: a vial adapter for holding a vial of the therapeutic agent; a pressure generating device for generating a positive pressure on an injection fluid; an infusion set having infusion tubing connected to an infuser, the infuser having a cannula assembly with a needle sized for injecting the therapeutic agent to the injection site; and a fluidics subassembly operably connecting the vial adapter, the pressure generating device and the infusion set, further comprising: an input port constructed to accept the injection fluid and move the injection fluid into a vial attached to the vial adapter; an output port constructed to receive the therapeutic agent from the vial, and move it toward the infusion set; wherein the infusion set further comprises an air evacuation assembly which further comprises a vented fluid chamber for venting air that is received into the chamber from the infusion tubing.

101. The medical device of claim 1, wherein the pressure generating device is a pressurized vessel, pressurized canister, or a peristaltic pump.

102. The medical device of claim 1, wherein the injection fluid is air or nitrogen.

103. The medical device of claim 1, wherein injection fluid is liquid or a liquid containing hyaluronidase.

104. The medical device of claim 1, wherein the pressure generating device has a pressure regulator.

105. The medical device of claim 1, wherein the input port operably couples to a check valve.

106. The medical device of claim 1, wherein the output port operably couples to a check valve.

107. The medical device of 100, wherein the therapeutic agent is a biologic.

108. The medical device of 107, wherein the biologic is injected in a volume 5 ml or greater.

109. The medical device of 107, wherein the biologic has a viscosity of greater than 10 cP.

110. The medical device of 100, wherein the therapeutic agent is a chemical drug.

111. The medical device of 110, wherein the chemical drug is injected in a volume of 5 ml or greater.

112. The medical device of 110, wherein the chemical drug has a viscosity of greater than 10 cP.

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