Components of open liquid drug transfer systems and a robotic system employing them

Abstract

Presented herein are a robotic system that is configured for compounding and preparation of medications comprising non-hazardous drugs and a vented drug vial adapter. The robotic system comprises: a laminar flow cabinet; and at least one robotic arm. The vented drug vial adapter is designed to connect a drug vial to another component of a drug transfer system. The adapter comprises a hydrophobic filter that prevents passage of liquid while allowing air to pass through it and a vent hole to the atmosphere. The vent hole is located above the filter thereby allowing equalization of the internal pressure while preventing the drug from contaminating the atmosphere.

Claims

1. A robotic system for compounding and preparation of medications including non-hazardous drugs, the robotic system comprising: a laminar flow cabinet; at least one robotic arm; and at least one vented drug vial adapter; wherein the at least one vented drug vial adapter and robotic system are configured to allow liquid to be drawn out of a drug vial and inserted into a drug vial; wherein said at least one vented drug vial adapter comprises: a liquid conduit extending at least partially through the at least one vented drug vial adapter; a top part comprising a hollow air chamber at least partially surrounding the liquid conduit, said top part further comprising a vent hole configured to allow fluid communication between the hollow air chamber and an exterior of the at least one vented drug vial adapter; a bottom part connected to the top part; and a hydrophobic venting filter positioned between the top part and the bottom part.

2. The robotic system of claim 1, further comprising: (i) at least two robotic arm assemblies configured to prepare syringes and intravenous (IV) bags comprising a prescribed amount of liquid drug for administration to patients according to their individual prescriptions by moving drug vials to which ventilated vial adapters have been connected and syringes within the laminar flow cabinet, (ii) cameras, and (iii) a system processor comprising software comprising imaging process algorithms that are adapted to provide real-time feedback control of all stages of the compounding process.

3. The robotic system of claim 2, wherein the at least two robotic arm assemblies are configured to move in three mutually orthogonal directions.

4. The robotic system of claim 3, further comprising at least two robotic arm assemblies configured to prepare syringes and IV bags comprising the required amount of liquid drug for administration to patients according to their individual prescriptions by moving drug vials, to which ventilated vial adapters have been connected, and syringes, to which connector sections have been connected, within the laminar flow cabinet and cameras and a system processor comprising imaging process algorithms that are adapted to provide real-time feedback control of all stages of the compounding process, wherein: a) the connector sections each comprise one of: (i) a septum holder comprising two resilient elongated arms that project vertically downwards parallel to each other attached to the side of the body part, each arm having distinctively shaped protrusions on the inner side of the distal ends of the arms; or (ii) a securing actuator section comprising at least one rung formed on the inside wall of the connector section and at least one rotatable gear comprising sprockets peripherally arranged around the gear, a void portion configured to house an anchoring ledge, and a gap formed in the gear such that the void portion is provided with an opening the orientation of which changes with the rotation of the gear; b) the ventilated drug vial adapters each comprise one of: (i) an upwardly projecting portion comprising a membrane at a proximal end and sockets on an outside proximal end, the sockets having a shape and dimensions configured to match those of the distinctively shaped protrusions on the inside of the arms of the septum holder; or (ii) an upwardly projecting portion comprising a membrane at a proximal end and anchoring ledges on an outside proximal end, the anchoring ledges having a shape and dimensions configured to pass through the gap and fit into the void in the gear of the securing actuator section of the connector; thereby allowing the connector sections to be connected only to drug vials connected to ventilated vial adapters comprising compatible sockets or anchoring ledges on the outside surface.

5. The robotic system of claim 4, wherein the distinctively shaped protrusions are on the outside of the upwardly projecting structure of the vial adapter and the matching sockets are on the inner side of the arms of the septum holder in the connector section and holder and on the distal end of the gripper assembly.

6. The robotic system of claim 4, further comprising a spike adapter configured for connection to an intravenous (IV) bag, the spike adapter comprising: a) a body terminating in a spike element at the proximal end of the body, the spike element comprising separate liquid and air channels; b) a standard port for connecting an infusion set at the distal end of the body, the standard port in fluid communication with the air channel in the spike; and c) a longitudinal extension connected substantially at right angles to the body, the proximal end of the longitudinal extension comprising a membrane and configured to be coupled with the connector section, and the longitudinal extension comprising a liquid channel in fluid communication with the liquid channel in the spike; the spike adapter characterized in that the longitudinal extension comprises one of: (i) a socket having a shape and dimensions configured to match those of the distinctively shaped protrusions on the arms of the septum holder; or (ii) anchoring ledges having a shape and dimensions configured to pass through the gap and fit into the void in the gear of the securing actuator section of the connector section; thereby allowing the spike adapter to be connected only to the connector section of claim 4.

7. The robotic system of claim 4, wherein the cameras and software are configured to recognize the sockets, protrusions, the gaps, void portions and anchoring ledges and to warn the user if the wrong components are introduced into the cabinet; and the robotic arm assemblies comprise mechanical features to insure that only the components compatible with an open transfer system are being used.

8. The robotic system of claim 3, wherein the at least two robotic arm assemblies are configured to pick up, move, and release syringes comprise special mechanisms to grip the connector and the syringe in varying orientations and the system requires software configured to deal with various syringes and various orientations, identifying them and reading the right dosage; thereby allowing the system to use conventional syringes from various manufacturers and various shapes and dimensions.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1a and FIG. 1b are schematic cross-sectional views of a prior art apparatus for transferring hazardous drugs without contaminating the surroundings;

(2) FIG. 2 and FIG. 3 show respectively a perspective view and a cross sectional view of a prior art vial adapter that is designed to be a part of an apparatus for transferring hazardous drugs without contaminating the surroundings;

(3) FIG. 4 is a cross-sectional view of the prior art vial adapter of FIG. 2 and FIG. 3 modified to comprise a hydrophobic filter membrane;

(4) FIG. 5a to FIG. 12 are different views showing another embodiment of a prior art vial adapter that is designed to be a part of an apparatus for transferring hazardous drugs without contaminating the surroundings;

(5) FIG. 13 is a cross sectional view showing a prior art spike adapter used in conjunction with fluid transfer apparatus and connector section to transfer a drug to and from an intravenous (IV) bag;

(6) FIG. 14 schematically shows an exploded view of a septum holder for a single membrane seal actuator in a connector section;

(7) FIG. 15a is a cross-sectional view schematically showing a vial adapter that is adapted for use in an open transfer system;

(8) FIG. 15b schematically shows the paths of two-directional flows of liquid and air through the vial adapter of FIG. 15a;

(9) FIG. 16a and FIG. 16b show alternative locations for the vent hole in the vial adapter of FIG. 15;

(10) FIG. 17 shows another embodiment of vial adapter designed for use with an open transfer system;

(11) FIG. 18a shows an open transfer system partially assembled for use;

(12) FIG. 18b shows a cross-sectional view of the open transfer system of FIG. 18a in its blocked configuration;

(13) FIG. 18c shows a connector section in the open transfer system of FIG. 18a;

(14) FIG. 19a shows the open transfer system of FIG. 18a in its fully assembled configuration for transfer of fluids;

(15) FIG. 19b is a cross-sectional view of the open transfer system of FIG. 19a;

(16) FIG. 19c is a zoom-in of section A in FIG. 19b focusing on the vial adaptor and the connected syringe connector;

(17) FIG. 20a and FIG. 20b schematically illustrate the elements that allow connecting together two components of an open transfer system and prevent an open transfer component from connecting with a closed transfer component;

(18) FIG. 21a schematically illustrate a spike adapter for connection to an IV bag;

(19) FIG. 21b is the cross-sectional view of the spike adapter of FIG. 21a;

(20) FIG. 22a is a schematic view of the interior of the safety cabinet of a robotic system for preparing drugs and medications for administration to patients;

(21) FIG. 22b schematically shows vial robotic arm assembly;

(22) FIG. 22c schematically shows the vial gripper assembly;

(23) FIG. 22d schematically shows the syringe pump robotic arm assembly;

(24) FIG. 22e schematically shows the syringe pump;

(25) FIG. 23 schematically illustrates a perspective view of a prior art female connector body;

(26) FIG. 24 is a perspective view of a prior art securing actuator;

(27) FIG. 25 is a cutaway perspective view of the female connector body of FIG. 23 with the securing actuator of FIG. 24 present therein;

(28) FIG. 26 is a cross-section view of an upper part of a prior art male connector;

(29) FIGS. 27a-27c are cutaway perspective views of a prior art male section inserted into the female connector body of FIG. 23 in multiple sequential positions;

(30) FIG. 28 is a cross-section showing the female connector of FIG. 23 where the actuator of FIG. 24 has been pushed up artificially for clarity purposes without inserting a male connector, thus exposing the needles that have passed through the actuator's membrane; and

(31) FIG. 29 shows a cross-section of the male and female connectors of FIGS. 26 and 25, in a position in which they have been brought into close proximity such that their relative membranes press on one another thus preventing liquid leakage, and the needles have perforated both membranes and are located inside the vial, viewed from the front.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

(32) For more than a decade the applicant of the present application has been engaged in development, manufacture, and sales of components of closed system liquid transfer devices designed to provide contamination-free transfer of hazardous drugs. These products are used to reconstitute powdered drugs and to transfer hazardous drugs in liquid form between drug vials, syringes, and IV bags. Some of the products developed and a robotic system that utilizes them for automatic preparation of prescriptions are described in the background section of this application. The present invention relies on the work done to date on the components for closed systems to develop similar components for use in the preparation of prescriptions involving non-hazardous drugs.

(33) Drugs are supplied by the manufacturers in vials as either liquids or powders. If in powder form then it must be reconstituted by addition of a measured amount of liquid diluent to the interior of the vial. In either case the preparation of a prescription involves drawing a measured amount of liquid drug from a vial into a syringe.

(34) FIG. 15a is a cross-sectional view schematically showing a vial adapter 300 that is adapted for use in an open transfer system. Vial adapter 300 comprises two parts a top part 304 and a bottom part 302. The structure of these two parts of vial adapter 300 and the telescopic way in which they lock together when connected to a drug vial is similar in most respects to the corresponding parts of vial adapter 200 described herein above with relation to FIG. 5a to FIG. 12.

(35) In contrast to the closed system vial adapter 200, the vial adapter 300 comprises only one conduitliquid conduit 308that passes through the entire vial adapter from the bottom of septum 322, which rests on septum seat 310 and seals the top of the vial adapter, through upwardly projecting structure 306, to the tip of spike 312.

(36) Vial adapter 300 comprises a hydrophobic filter 316. The filter is made of a thin disc shaped piece of hydrophobic material. A hole is cut through it to allow free passage of liquid through liquid conduit 308. The filter 316 is placed between a plurality of closely spaced supporting ribs from above and below and its outer and inner edges are welded, glued, or mechanically pressed to the top part 304 of vial adapter as described herein above with respect to FIG. 4.

(37) An air channel 314 through the spike terminates in an open space 324 beneath filter 316. The interior of the upwardly projecting structure 306 comprises a hollow air chamber 318 surrounding liquid conduit 308. Air chamber 318 is sealed at the top by septum 322 and at the bottom sealed to prevent the entrance of liquid by filter 316. A vent hole 320 near the top in the side of upwardly projecting structure 306 above filter 316 allows fluid communication between the interior of air chamber 318 and the air outside of the vial adapter.

(38) FIG. 15b schematically shows the paths of two-directional flows of liquid and air through the vial adapter of FIG. 15a.

(39) FIG. 16a and FIG. 16b show alternative locations in vial adapter 300 for the vent hole 320, which can be located at any place proximally, i.e. above or beyond, filter 316. A person skilled in the art can place and shape the venting feature in various places and ways.

(40) FIG. 17 shows another embodiment of vial adapter designed for use with an open transfer system. It is identical to vial adapter 15 shown in FIG. 4 with the exception that the air channel 56 has a vent hole 402 in its side that allows unhindered fluid communication between the interior of air channel 56 and the exterior of vial adapter 400. Vent hole 402 is located above filter 66. Pressure equalization takes place in vial adapter 400 exactly as described for vial adapter 300 described with reference to FIG. 15a and FIG. 15b.

(41) FIG. 18a shows an open transfer system partially assembled for use. The system comprises a vial adaptor 300 (see FIG. 15a) that is attached to a drug vial 16 and a conventional syringe 450 that is attached to an open system connector 452.

(42) FIG. 18b shows the cross-sectional view of the open transfer system of FIG. 18a. Shown in FIG. 18b are: conventional syringe 450, connector 452, and vial 16 with attached vial adapter 300.

(43) Also shown are upwardly projecting structure 306, septum 322, liquid channel 308, and vent hole 320 of vial adapter 300.

(44) FIG. 18c shows connector 452, which is similar to the prior art connector section 14 with the following modifications: (a) the double membrane seal actuator 34 shown in FIG. 1a is replaced with a septum holder 500 (shown in FIG. 14) comprising septum 572 at its bottom; and (b) there is only one needle 454 acting as a liquid conduit within connector 452. Connector 452 is shown in its blocked configuration.

(45) FIG. 19a shows the open transfer system of FIG. 18a in its fully assembled configuration after vial adapter 300 is connected to a drug vial and spike 312 has penetrated the membrane at the top of the vial as described herein above with reference to FIGS. 8-11. The vial adaptor 300 with attached drug vial 16 is connected to the conventional syringe 450 by means of connector 452.

(46) FIG. 19b is the cross-sectional view of the open transfer system of FIG. 19a. The FIG. 19c is a zoom-in of section A in FIG. 19b focusing on the vial adaptor with the connected syringe connector.

(47) Using the open transfer system shown in FIGS. 18a-19c, a drug in powdered form can be reconstituted by filling a conventional syringe 450 with the required amount of diluent, the syringe connector 452, which is connected to the syringe, is then pushed down over the upwardly projecting structure 306 of the open system vial adapter (FIGS. 18a and 18b) until the connection is established as shown in FIGS. 19a through 19c at which time the needle 454 of the connector 452 has penetrated through both the septum 572 of the septa holder in connector 452 and the septa 322 of the vial adaptor and has entered liquid conduit 308 in the vial adapter.

(48) After the connection is established the piston of the syringe 450 can be pushed downward forcing the liquid diluent to flow through needle 454 in the connector and liquid conduit 308 in the vial adapter into the interior of the vial (arrow B). As liquid enters the vial air is displaced and pressure is equalized by air flowing out of the vial through air channel 314 through hydrophobic filter 316 into air chamber 318 and out of the vial adapter through vent hole 320 (arrow C).

(49) To draw liquid out of a drug vial the connected vial and syringe connected as shown in FIGS. 19a-19c are flipped and inverted upside down so that the vial is located above the syringe. Following the inversion the piston of the syringe can be pulled downward drawing the liquid out of the interior of the vial through liquid conduit 308. As the liquid is drawn out of the vial a partial vacuum is created in the vial, which is equalized by suction which draws air into the vial from outside of vial adapter 300 through vent hole 320, air chamber 318, filter 316, and air channel 314.

(50) As mention above, the components of the closed systems can be used when compounding and filling prescriptions of hazardous and non-hazardous drugs; however the components of the open systems can be used only for non-hazardous drugs. In order to prevent interchangeability of the open and closed system components the applicant uses a different configuration of connecting elements to connect the components of each system.

(51) FIG. 20a and FIG. 20b schematically illustrate the elements that allow connecting together two components of an open transfer system and prevent an open transfer component from connecting with a closed transfer component. For illustrative purposes an open system septum holder 600, which is a component of a connector section, is to be connected to the upwardly projecting structure 306 of an open system vial adapter (see FIG. 15a) and the upwardly projecting structure 220 of a closed system vial adapter (see FIG. 6).

(52) Septum holder 600 is identical to septum holder 500 shown in FIG. 14 with the exception of the distal end of the inner facing side of the arms 662 that are connected to the body part of the septum holder. Septum 672 is shown fitted over the septum support. On the outer side of arms 662 are distal enlarged elements 668 and on the inner side of the arms opposite the enlarged elements 668 are distinctively shaped protrusions 602 comprising for example as shown, vertical and horizontal bars in the shape of an inverted letter L. As shown in FIG. 20a, the upwardly projecting structure 306 comprises a socket 604 in the shape of an inverted letter L on its side below septum 622. Socket 604 has a shape and dimensions which match those of the distinctively shaped protrusions 602 on the arms of the septum holder allowing protrusions distinctively shaped 602 to fit into sockets 604 connecting the septum holder to the vial adapter. On the other hand, the components of the closed system comprise protrusions and sockets having other shapes than those of the components of an open system, for example for a closed system, the protrusion on the arms could be a vertical bar and the socket a vertical slot. In this case, as shown in FIG. 20b, the horizontal bar at the top of distinctively shaped protrusion 602 will prevent protrusion 602 from entering vertical socket 606 on the upwardly projecting structure 220 of the closed system vial adapter, thereby preventing connecting the open system septum holder to the closed system vial adapter. It is noted that the shapes of the protrusions and sockets described are for illustrative purposes only and many other distinctive shapes could be used for the same purpose.

(53) FIG. 21a schematically shows a spike adapter 700 used in conjunction with fluid transfer apparatus 10 to transfer a drug to and from an intravenous (IV) bag. Spike adaptor 700 comprises body 762 terminating in a spike element 764 at the proximal end and a standard port 766 for connecting an infusion set at the distal end. Substantially at right angles to body 762 is a longitudinal extension 768. At the end of longitudinal extension 768 are membrane enclosure 770 and membrane 772. On the side of longitudinal extension 768 below membrane enclosure 770 is a socket 604 configured to match with the distinctively shaped projections on the arms of a septum holder in a connector as shown in FIG. 20a. A connector section, e.g. connector 452 (see FIG. 18) with attached conventional syringe can connect to longitudinal extension 768 exactly as described herein above with respect to connection to vial adaptor 300 in FIGS. 19a-19c, thereby allowing insertion of a drug from the syringe into an IV bag or withdrawal of liquid from an IV bag into a syringe to be used for reconstitution of a drug.

(54) FIG. 21b is a cross-sectional view of the spike adapter. In this figure can be seen that the interior of spike adapter 700 comprises two separated channels 774 for liquid and 776 for air. In this open system spike adapter liquid channel 774 passes from the tip of spike element 764 to membrane 772 for use if liquid is to be transferred into or out of the IV bag from a syringe. Channel 776 passes from the tip of the spike to port 766 to transfer liquid from the IV bag to the patient. In an open system for injection or withdrawal of liquid from a syringe to an IV bag there is no need for venting because, unlike a stiff glass vial, an IV bag is flexible allowing it to expand when pressurized or contract when it is evacuated.

(55) The apparatus for securing a male-female connection described with respect to FIGS. 23-29 can easily be modified mutatis mutandis for use with an open drug transfer system. For the open system, the female connector, e.g. the connector section 452 in FIGS. 18a-18c would have only one needle and septum holder 500 could be replaced with the ladders, gears, and other features of female connector 1201. The vial adapters vial adapters of FIGS. 15a and 17 and the spike adapter of FIG. 21a would also be modified such that their upwardly projecting structures 306, 46, and 768 would have smooth sides and two anchoring ledges 1223 on opposite sides near the top.

(56) Referring to FIG. 27a, it can be seen how the components are configured to prevent connection of open and closed system components together. For example, for a closed system the ledge 1223 can be wider than the gap 1406 in gear 1405 of the securing actuator 1401 for an open system, thereby preventing connection of a closed system vial adapter to an open system connector 1201. Alternatively, for an open system the ledge 1223 can be wider than the gap 1406 in gear 1405 of the securing actuator 1401 for a closed system, thereby preventing connection of an open system vial adapter to a closed system connector 1201.

(57) The components of an open system described herein have been developed for use in a robotic system that can be installed in hospital pharmacies to assist in the compounding of medications comprising non-hazardous drugs and to prepare syringes and IV bags comprising the required amount of liquid drug for administration to patients according to their individual prescriptions. The robotic system is similar to the one described in the background section for use with hazardous drugs and shown in FIG. 22. In compliance with regulations the two robotic systems will be kept in separate rooms in the pharmacy.

(58) For non-hazardous drugs the safety requirements are much less restrictive; however, exactly as in the case of the system for hazardous drugs, the system comprises at least two robotic arm assemblies configured to simultaneously move vials and syringes within the cabinet. Each of the robotic arm assemblies comprises three mechanical arrangements configured to independently move either a vial gripper assembly or a syringe gripper assembly and syringe pump in three dimensions along three mutually orthogonal beams. Within the laminar flow cabinet is a plurality of operational stations adapted to perform specific tasks related to the compounding process. The operating stations include: at least one reconstitution module; at least one vial shaker module; at least one vial flipper module; at least one IV bag base module to which the operator of the system can attach IV bags; a syringe magazine; a plurality of cameras each installed at a specific location in the cabinet or on the robotic arm assemblies, and a processor. Each of the cameras is dedicated to provide real time digital images of the stage of the preparation process carried out at its location. Dedicated software and algorithms in the system processor allow almost all steps in the compounding process to be carried out automatically by the robotic arm assemblies without intervention by the operator or a supervisor and the cameras and imaging process algorithms are adapted to provide real-time feedback control of all stages of the compounding process.

(59) One important difference between the robotic system developed for the closed transfer system and one for use in an open system is that the that closed transfer system relies on the use of Equashield syringes that have to be manufactured in perfect orientation and alignment with their connectors. This is important because the Equashield syringes will be gripped and placed when the connector extending shoulders and the extensions on the syringe barrel are always in same position relative to each other and due to this identical orientation only simple griping mechanisms are required and processes of placing and handling the syringes is an easy and fast task to accomplish. Unlike the well aligned Equashield syringes, the open transfer system uses conventional syringes from various manufacturers and various shapes and dimensions, and the connector shoulders on the arms and the extensions on the syringe barrel are seldom in same position relative to each other, a fact that requires special mechanisms integrated into the robot to grip the connector and the syringe in varying orientations. This also requires software that can deal with various syringes, various orientations, identifying them and reading the right dosage.

(60) In using the robotic system, the prescriptions to be filled are entered into the system processor, which prompts the user to insert drug vials containing the required medicines into the cabinet, to load syringes of the required sizes into the syringe magazine, and attach IV bags to the IV bag base modules.

(61) In order for the robotic arms to be able to grab the vials and syringes, the user connects a vial adapter to each vial and a connector section to each syringe before placing them in the cabinet. After the drug vials, syringes, and IV bags are placed in the cabinet, all further operations of compounding the drugs and preparing the required doses in syringes or IV bags for administration to a patient are carried out automatically by the robotic arms as instructed by the processor under supervision of the cameras.

(62) In the open transfer robotic system the cameras and software are configured to recognize the sockets 604 and protrusions 602 on the vial adapter 220 and septum holder 600 in FIGS. 20a and 20b and the gaps 1406 and void portions 1405 in the securing actuator and ledges 1223 on the male connector 1221 in FIGS. 24 and 26 and to warn the user if the wrong components are introduced into the cabinet. Additionally, as a safety feature, the robotic arm assemblies comprise mechanical features, e.g. projecting pins that must fit matching slots on the components to be picked up, to insure that only the components compatible with an open transfer system are being used.

(63) Open transfer components for use with the robotic system constitute two kitsa basic kit will contain a vial adapter and a connector section and an extended kit that additionally contains an IV spike adapter. The kits will come in several embodiments to include vial adapters suitable for different sized vials and connectors have different types of connections, e.g. Luer lock or bayonet connectors to mate with standard needless syringes.

(64) Although embodiments of the invention have been described by way of illustration, it will be understood that the invention may be carried out with many variations, modifications, and adaptations, without exceeding the scope of the claims.