Piston valve for serially connectable drug modules of a combination drug delivery device

Abstract

A valve arrangement for regulating the flow path of modules that can be used in combination drug delivery devices is provided herein. The valve includes a slidable piston valve that is adjustable to selectively seal an outlet path from a drug vial and a sealing port that is parallel to a vent for selectively sealing an inlet path to the drug vial. Advantageously, the present invention allows for the application of negative pressure to regulate the valve to allow flow between modules that are connected in series to form a drug delivery device.

Description

TECHNICAL FIELD

[0001] The technical field of the present invention is the compounding and preparation of liquid pharmaceuticals, particularly for intravenous infusion and direct patient infusion. More particularly, the present invention relates to a sealing mechanism for a device for the preparation and compounding of a combination of two or more pharmaceuticals. BACKGROUND

[0002] When administering pharmaceuticals by intravenous infusion, it is common practice to compound the pharmaceutical in a pharmacy environment. Such pharmaceuticals are typically provided aseptically in glass vials and can be provided in solid form or in aqueous solution. When provided in solid form, the pharmaceutical must be reconstituted with a sterile aqueous diluent prior to transfer to an infusion bag. Those skilled in the art will appreciate that such pharmaceutical formulations will typically include several excipients, such as buffers, pH adjusters, tonicity adjusters, stabilizers, etc. Typically, the liquid pharmaceuticals for intravenous infusion are compounded in an infusion bag in a pharmacy environment prior to being transferred to a patient for infusion. Since it is necessary to maintain the sterility of the pharmaceuticals while compounding, the compounding procedure is typically performed in a sterile pharmacy hood. Typically, a pharmacist or pharmacy technician (practitioner) will prepare the pharmaceuticals according to individual patient prescriptions.

[0003] After ensuring that the pharmacy hood is free of any matter, the practitioner will remove the vials required for the prescription from pharmacy inventory and verify their identity and concentration. The verification process can be aided by the use of bar code scanners or other identification techniques. The practitioner will also select from inventory all other necessary equipment required to safely prepare the pharmaceuticals for infusion, including the infusion bag itself, syringes, needles, transfer sets, gloves, sharps disposal containers, etc. Once all necessary equipment is assembled, the practitioner will follow the protocol for preparing the pharmaceuticals, which can include reconstituting solid pharmaceuticals by adding diluent, sequentially withdrawing liquid pharmaceuticals from their respective vials via transfer ports into the IV bag. Typically, this procedure is performed manually and involves the use of multiple needles. Each needle required to effect pharmaceutical compounding increases the risk of needle stick injury to the practitioner. In the case of high potency or highly toxic pharmaceuticals (e.g., cytotoxic agents used in chemotherapy), this presents a significant exposure risk to the practitioner.

[0004] In order to eliminate some risks associated with manual preparation (including the risk of being exposed to hazardous drugs and medication negligence), pharmaceutical compounding machines that are known to those skilled in the art to automate many steps involved in drug preparation and preparation are known. Typically, such machines are complex electromechanical systems that have realized a precision dispensing mechanism for accurate reconstruction of liquid drugs. In addition to their cost, size and complexity, many designs for such machines described in the art extract liquid drugs from library storages, and therefore only use a small portion of the drug in the container. Due to the need to maintain sterility, unused drug solutions must usually be discarded and therefore wasted. Since the cost of some drugs (particularly biopharmaceuticals) is very high, this waste is a considerable cost. When the wasted drug is a cytotoxic agent, their disposal can produce significant environmental hazards and safety hazards.

[0005] Recent advances in medicine, particularly in cancer treatment, have demonstrated that therapeutically beneficial effects can be achieved through synergistic combinations of two or more drugs.

[0006] For example, recent clinical studies have shown that the combination of anti-PD-1 checkpoint inhibitors and CTLA4 checkpoint inhibitors can have beneficial synergistic effects in certain tumor types, which can lead to better clinical outcomes than administering either drug alone. Typically, such checkpoint inhibitor drugs are biotechnology-derived immunoglobulin-type monoclonal antibodies or fragments thereof. In some cases, it can be beneficial to use such biologic drugs in combination with conventional chemotherapy drugs such as cytotoxic drugs.

[0007] By using the serially connectable drug modules described in the applicant's co-pending applications (U.S. Provisional Patent Application No. 62 / 670,266, filed May 11, 2018; PCT Application No. PCT / US2019 / 031727, filed May 10, 2019; PCT Application No. PCT / 2019 / 031762, filed May 10, 2019; PCT Application No. PCT / US2019 / 031791, filed May 10, 2019), drug combinations can be successfully stored, transported, and administered to patients in a manner that allows sufficient flexibility while minimizing product waste. These drug modules use common, off-the-shelf vial primary containers that are pierced by a spike located inside the module during administration, allowing the liquid drug within the vial to enter the module's internal flow path. The key is the presence of a sealing mechanism within the module's flow path that not only confines the liquid drug product within the module's flow path during puncture, but also opens the fluid path to allow drug product flow during product use. Because this product is envisioned as disposable, the ideal sealing mechanism must be inexpensive to produce while also being highly reliable and repeatable.

[0008] Applicants have now recognized that the combined principles described in the following patent applications: U.S. Provisional Patent Application No. 62 / 670,266, filed May 11, 2018, PCT Application No. PCT / US2019 / 031727, filed May 10, 2019, PCT Application No. PCT / 2019 / 031762, filed May 10, 2019, and PCT Application No. PCT / US2019 / 031791, filed May 10, 2019, which have the same assignee as this patent application and are incorporated herein by reference in their entirety, can address several challenges encountered in the preparation and compounding of intravenous infusion drugs and can provide several advantages, including but not limited to simplifying the dispensing procedure, reducing the risk of medication errors, curbing and protecting practitioners from the hazards of highly potent or highly toxic drugs, reducing the risk of needlestick injuries, reducing or eliminating drug waste, and avoiding the need for complex and expensive pharmaceutical compounding machines. Due to these advantages in the embodiments, the present invention can further enable the preparation and dispensing of medications for IV infusion at locations remote from the pharmacy and by non-professional practitioners (e.g., by a properly trained technician or nurse in the patient's home). The inherent portability of the systems described herein enhances this possibility. Summary of the Invention

[0009] According to the present invention, for a module usable with a combination drug delivery device, a movable piston seal having a bypass chamber inline with the module outlet fluid path provides a method of sealing the module's fluid path from the atmosphere during vial piercing, while also being capable of allowing the fluid path to open when a vacuum is applied to the outer surface of the piston seal.

[0010] Two inlet and outlet cavity pathways, located within the tip that accesses the vial's medication chamber, separate the module's fluid pathways. The inlet pathway allows liquid drug product from the previously connected module to enter the inserted vial, while the outlet pathway moves fluid from the vial to the next module. A spring-loaded seal at the inlet pathway entrance, designed to engage the preceding module, ensures the pathway is open only when connected to a module. Therefore, once a vial is inserted, the inlet pathway is closed to atmosphere, preventing the vial's contents from escaping.

[0011] During vial penetration, the volume of the tip entering the vial displaces some of the fluid within the vial, causing the vial contents to be slightly pressurized, forcing them into the tip cavity. On the inlet side, this pressure is limited by a spring-loaded seal, and on the outlet side, the fluid enters the tip cavity and is sealed by the piston seal. Any pressure during the penetration process pushes slightly on the piston seal, allowing the liquid chamber to increase in volume, thereby reducing the pressure caused by the penetration. On the opposite side of the piston seal is the outlet to the inlet of the next module. A small bypass is cut into the module body near the piston seal that connects the outlet chamber to the outlet connector. When a vacuum source is applied to the outlet connector, this causes the piston to move, exposing the bypass port to the fluid path of the vial, thereby opening a path for fluid to move from the vial to the outlet connector. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 shows a piston valve according to the present invention in a closed position;

[0013] Figure 2 Shown is a piston valve for releasing positive pressure in a vial according to the present invention;

[0014] Figure 3 shows a piston valve according to the present invention in an open position;

[0015] Figure 4 A drug vial coupled to a valve according to the present invention is shown;

[0016] Figure 5 shows piston valves connected in series according to the present invention; and,

[0017] Figure 6 The fluid paths of the piston valves connected in series according to the present invention are shown. DETAILED DESCRIPTION

[0018] The present invention is particularly suitable for use with drug modules connected in series, particularly to form fluid paths between them. The present invention is shown in the context of a single module 9, but it will be appreciated that the present invention can also operate with a plurality of similarly formed modules 9 connected in series. Figure 1 and Figure 4 As shown, each module 9 includes a valve having a vial tip 1 for piercing a vial septum S extending into the interior volume V of a liquid-filled drug vial DV. A free distal end 11 of the vial tip 1 may be pointed to facilitate piercing the vial septum S. The vial tip 1 must be of sufficient length to completely pierce the septum S upon entering the interior volume V.

[0019] The vial tip 1 includes two cavities that separate the module flow path into independent circuits, namely, an inlet path 2 and an outlet path 3. When the vial tip 1 pierces the septum S, both the inlet path 2 and the outlet path 3 are open at the free end 11 of the vial tip 1 and communicate with the internal volume V of the drug vial DV. The inlet path 2 extends from the internal volume V of the drug vial DV to an inlet opening 12, which is selectively sealed by a spring-biased sealing port 4. On the inlet path 2, there is preferably a vent 10 between the free end 11 and the inlet opening 12 to allow air to enter the drug vial DV as needed to displace the fluid during transfer. Preferably, the vent 10 is a one-way vent that is normally closed and allows airflow to enter the inlet path 2. The outlet path 3 extends downward from the internal volume V of the drug vial DV to the outlet chamber 6. The piston valve 5 is slidably mounted in the outlet chamber 6, establishing a seal against the inner wall 13 of the chamber. The piston valve 5 may include a radial seal 14 in sealing contact with the wall 13 to define a seal while allowing the piston valve 5 to slide within the outlet chamber 6 .

[0020] Piston valve 5 forms a seal within outlet chamber 6 to define a first chamber portion 6a and a second chamber portion 6b. The sizes of the first and second chamber portions can be adjusted as piston valve 5 moves within outlet chamber 6 while maintaining a seal therebetween. Outlet path 3 communicates with first chamber portion 6a. An outlet connector 7 is provided to communicate with outlet chamber 6, particularly with second outlet chamber 6b.

[0021] In the initial state, if Figure 1 As shown, the piston valve 5 is in a first position at the middle end of the outlet chamber 6, preventing fluid entering from the outlet chamber 3 from entering the outlet connection 7. A bypass channel 8 connects the outlet chamber 6 to the outlet connection 7. In particular, the bypass channel 8 terminates at an opening 15 in a wall 13 of the outlet chamber 6. With the piston valve 5 in the first position, the first chamber portion 6a is sealed relative to the bypass channel 8.

[0022] With this arrangement (piston valve 5 is in the first position), and as Figure 2 As shown, as the vial tip 1 penetrates the septum S, pressurized fluid forced from the drug vial DV will be contained in the inlet passage 2 by the spring biased sealing port 4, while any fluid entering the outlet passage 3 will be contained in the first chamber portion 6a behind the piston valve 5. Figure 2 As shown, the pressure in the fluid may cause the piston valve 5 to move slightly; this movement in position will equalize the pressure within the drug vial DV and the fluid path to a negligible amount.

[0023] like Figure 3As shown, when the fluid is transferred, a negative pressure source (e.g., vacuum) will be provided to the outlet connector 7, thereby exhausting air from the bypass channel 8 and the outlet chamber 6, especially from the second chamber portion 6b. This will generate a pressure difference on the piston valve 5, which will cause the piston valve 5 to slide along the outlet chamber 6 toward the outlet connector 7. This causes the volume of the first chamber portion 6a to increase. Finally, when the piston valve 5 continues to move, the piston valve will pass through the bypass channel 8, thereby allowing the first chamber portion 6a, together with the outlet path 3, to communicate with the bypass channel 8. Figure 3 As shown, with a vacuum applied to the bypass channel 8 , fluid will be able to flow from the vial through the outlet passage 3 , through the bypass channel 8 , which bypasses the piston valve 5 , and out through the outlet connector 7 .

[0024] like Figure 5 and Figure 6 As shown, a plurality of modules 9 can be coupled in series to the outlet connector 7a of a secondary module 9a, which breaks through the sealed port 4 of an adjacent module 9 so that the outlet connector 7a communicates with the inlet opening 12 of the adjacent module 9. The secondary module 9a is formed similarly to the module 9, with similar components having similar reference numerals, but additionally designated with the letter "a" (except for the outlet chamber of the secondary module, which is designated 6'). The coupling arrangement allows for the definition of a fluid path from the drug vial DV coupled to the vial tip 1a of the secondary module 9a, through the drug vial DV coupled to the vial tip 1, to the outlet connector 7 of the module 9, as shown. Figure 6 This fluid pathway is schematically shown in FIG. This fluid pathway is achieved through the sliding movement of piston valve 5a, which is induced by negative pressure applied to outlet connector 7a via outlet path 3 and inlet path 2 of module 9. In a manner similar to that described above, when the sliding displacement of piston valve 5a is sufficiently large, liquid flows past piston valve 5a via bypass channel 8a. This arrangement allows a series of modules 9 to be coupled, with corresponding drug vials DV aligned in a straight line, defining a single flow path driven by a single negative pressure source.

[0025] It is also noted that the vent 10 can be positioned to terminate at a vent opening 16 that is positioned to be exposed to the open atmosphere. Preferably, the vent opening 16 is located on a common wall with the sealing port 4 so that the adjacent coupled module 9a covers the vent opening 16. This obstruction limits ventilation in the module 9, thereby maximizing the negative pressure applied to the adjacent coupled module 9a. The obstructed ventilation can continue in a series of coupled modules, wherein the final module 9 (e.g., module 9a) has an exposed vent opening 16, thereby providing ventilation for the entire series.

Claims

1. A module for a combined drug delivery device, the module being formed to receive a drug vial having a septum, the module comprising: a vial tip formed to pierce a septum of the drug vial, the free end of the vial tip being located within the septum, the vial tip including an inlet path opening at the free end and extending along the vial tip to an inlet opening, and an outlet path opening at the free end and extending along the vial tip to an outlet chamber, the outlet path being separate from the inlet path; a sealing port for selectively sealing the inlet opening; a vent in communication with the inlet path between the inlet opening and the free end; a slidable piston valve positioned in the outlet chamber, the piston valve forming a seal in the outlet chamber to define a first chamber portion and a second chamber portion, the outlet path communicating with the first chamber portion; an outlet connector in partial communication with the second chamber; and a bypass channel extending between the outlet connection and an opening in the outlet chamber, wherein, in an initial state, the piston valve is located in a first position, in which the first chamber portion is sealed relative to the bypass channel, and Wherein, when negative pressure is introduced through the outlet connection, the piston valve is caused to move to a second position, in which the first chamber portion is connected to the bypass channel.

2. The module of claim 1, wherein the vent is a one-way vent that is normally closed and allows airflow into the inlet path.

3. The module of claim 1 , wherein the piston valve includes a radial seal in sealing contact with a wall of the outlet chamber.

4. A module combination comprising: A first module, the first module comprising: a first vial tip having a first free end, the first vial tip comprising a first inlet path open at the first free end and extending along the first vial tip to a first inlet opening, and a first outlet path open at the first free end and extending along the first vial tip to a first outlet chamber, the first outlet path being separate from the first inlet path; a first sealing port for selectively sealing the first inlet opening; a first vent in communication with the first inlet path between the first inlet opening and the first free end; a first slidable piston valve positioned in the first outlet chamber, the first piston valve forming a seal in the first outlet chamber to define a first primary chamber portion and a second primary chamber portion, the first outlet path being in communication with the first primary chamber portion; a first outlet connection communicating with the second primary chamber portion; and a first bypass channel extending between the first outlet connection and a first opening in the first outlet chamber, The second module includes: a second vial tip having a second free end, the second vial tip including a second inlet path open at the second free end and extending along the second vial tip to a second inlet opening, and a second outlet path open at the second free end and extending along the second vial tip to a second outlet chamber, the second outlet path being separate from the second inlet path; a second sealing port for selectively sealing the second inlet opening; a second vent in communication with the second inlet path between the second inlet opening and the second free end; a slidable second piston valve positioned in the second outlet chamber, the second piston valve forming a seal in the second outlet chamber to define a first secondary chamber portion and a second secondary chamber portion, the second outlet path communicating with the first secondary chamber portion; a second outlet connection communicating with said second secondary chamber portion; and a second bypass channel extending between the second outlet connection and a second opening in the second outlet chamber, wherein the second module is coupled to the first module, and the second outlet connector extends through the first sealing port to communicate with the first inlet opening; wherein, in an initial state, the first piston valve is located in a first position, in which the first primary chamber portion is sealed relative to the first bypass channel, wherein, in case of introduction of negative pressure via the first outlet connection, the first piston valve is caused to move to a second position in which the first primary chamber portion is in communication with the first bypass channel, and When the first piston valve is in the second position, the negative pressure is introduced into the second outlet connection via the first outlet path and the first inlet path. 5 . The module combination according to claim 4 , wherein the first vent is covered by the second module when the second module is coupled to the first module. 6 . The module combination of claim 4 , wherein with the second module coupled to the first module, the second vent is exposed and the second sealing port seals the second inlet opening.

7. The modular combination according to claim 4, wherein: When the negative pressure is introduced through the second outlet connection, the second piston valve is caused to move within the second outlet chamber to connect the first secondary chamber portion with the second bypass channel.

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