Disposable Volumetric Dosing Pump Kit

Abstract

A novel disposable volumetric pump that meets the stringent requirements for use in sterile environments in the pharmaceutical and / or biomedical industries. A kit comprising a single-acting pump (1) having an inlet (21) connecting line and an outlet (31) connecting line, the connecting line being made of a flexible material that allows the line to be occluded when pinched. A drive system (50) adapted to operate the kit is also provided, in which the pinching means is configured to alternately pinch the connecting line fixed to the inlet and the connecting line fixed to the outlet in synchronization with the movement of the piston (11).

Description

[Technical Field]

[0001] The present invention relates to the field of volumetric pumps, particularly disposable pumps for use in sterile environments. [Background technology]

[0002] Industries such as the pharmaceutical or medical industry use volumetric pumps to fill individual containers with liquid preparations, e.g., medicinal preparations (vaccines) into syringes, solutions into pouches for intravenous administration, etc. It is of utmost importance that the liquid preparation is free of foreign particulates, remains sterile, and that the volume dispensed is very precise, even for very small volumes of less than 1 mL or even less than 0.1 mL.

[0003] To achieve these goals, high-precision positive displacement pumps have been developed in a variety of materials, such as stainless steel or ceramic, the latter being widely used by pharmaceutical manufacturers to eliminate the risk of contamination from chromium often associated with metal pumps.

[0004] These pumps are typically constructed around a central axis defined by a cylinder hollowed out within a casing, with a piston slidably movable longitudinally at a predetermined amplitude to define a metering chamber with a predetermined volume. Such systems are also called piston pumps. Check valves are typically located at the pump's inlet and outlet, as in U.S. Patent No. 5,629,994. In some other cases, known as two-element piston pumps, additional channels are located within the piston that rotate about the axis to alternately connect the metering chamber to the pump's inlet and outlet nozzles, thus functioning as a selector valve. In other cases, known as three-element pumps, the selector valve is incorporated into a separate element also inserted into the cylinder. In this latter case, the piston operates via a sliding element, while the selector valve operates via a separate rotating element. Those skilled in the art are familiar with these pumps, and U.S. Patent No. 5,629,994 discloses how such pumps function.

[0005] The inlet is connected via tubing to a bulk tank of liquid for dispensing, and the outlet is usually connected via tubing to a needle for final dispensing in a final container.

[0006] Volumetric pumps need to be cleaned and sterilized regularly to avoid contamination from various particles, cross-contamination (i.e., contamination between pharmaceutical preparations of different compositions) or bacteriological growth, for example when starting a new manufacturing batch.

[0007] Cleaning procedures must be developed, implemented, and verified for compliance by pharmaceutical manufacturers for all product and used filling equipment that comes into direct contact with such products. This means that cleaning validation documentation must be prepared and testing must be conducted to prove that the defined cleaning method results in the required equipment cleanliness and sterility, and therefore patient safety. Such validation processes typically take several months and must be performed again when the filling equipment or product is changed. This places significant pressure on manufacturers, as it allows for little flexibility and significantly extends product time to market.

[0008] To overcome this problem, disposable pumps have been developed and used by manufacturers for a long time. Disposable pumps allow the validation burden to be shifted to the pump manufacturer rather than the end-product manufacturer. For many years, the most common solution has been the peristaltic pump, which has been widely used by pharmaceutical manufacturers as a disposable alternative to volumetric pumps.

[0009] The challenges of disposable pumps are to combine high precision at small volumes (i.e., volumes less than 0.3 ml) in scale-up manufacturing conditions, compatibility with viscous products, compatibility with biopharmaceuticals (i.e., protein-based products) that occupy the growing gene therapy market, and product quality after filling. Other challenges include installation in isolators while maintaining aseptic operation.

[0010] Therefore, the applicant has determined that there is a need to propose a new disposable volumetric pump that meets the stringent compliance requirements in the pharmaceutical and / or biomedical industry. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] European Patent Application Publication No. 2140892 [Patent Document 2] European Patent No. 3045724 Summary of the Invention

[0012] For this purpose, a kit is proposed, which comprises: a single-acting pump having a piston slidably disposed within a cylinder body, the cylinder body being disposed with an inlet and an outlet that both allow fluid communication between the exterior of the cylinder and a metering chamber inside the cylinder body, said metering chamber being further defined by one end of the piston located within the cylinder body, the other end of the piston protruding from the cylinder body; a connecting line fixed to the inlet; a connecting line fixed to the outlet, The connecting line is made of a flexible material that allows the line to be blocked when pinched.

[0013] Preferably, the end of the piston which projects from the cylinder body is provided with means for fastening to an external machine for driving translational movement of the piston.

[0014] The kit of the present invention represents an assembly of components. The kit is sterile and ready to use. It is a "disposable kit", meaning that it does not undergo any cleaning operations between batches or lots, but is instead discarded and replaced.

[0015] This is preferably provided in a package, such as a sealed double bag, to ensure sterile storage from the manufacturer's site to the point of use.

[0016] The purpose of the kit is to prevent end users from making connections between the pump and connecting lines in a Grade A environment, a delicate operation that poses a contamination risk. Furthermore, these operations are usually performed in an isolator, which is not only sensitive to contamination but also difficult to perform with gloves, and there is a risk that the connection will not be made properly and will fail during pump operation.

[0017] Preferably, the connecting line secured to the inlet comprises a sterile connector for connecting the line to the bulk tank, which maintains the sterility of the filling circuit and protects it from foreign matter.

[0018] Preferably, the connecting line secured to the outlet comprises an end needle for dispensing the liquid into the final container, the end needle preferably being inserted into a protective holster or case to prevent the needle from puncturing the packaging and / or injuring the user.

[0019] In a preferred embodiment, the kit of the present invention comprises several pumps and an equal number of inlet and outlet connection lines, the inlet connection lines being arranged downstream of a single main inlet line. In this configuration, several pumps are arranged in parallel to be supplied from a single supply tank. This means that the main inlet line is divided into several inlet connection lines, each inlet connection line being connected to the inlet of a pump, and each pump having an outlet connection line. This arrangement allows for parallel dispensing into several containers to speed up the process.

[0020] The pump in the kit comprises a cylinder body, which means that the cylinder is closed at one end (except for the inlet and outlet), and the other end is open to allow the piston to slide in. The cylinder body has a cylinder axis.

[0021] In this case, the pump consists of a cylinder hollowed out in a casing and a linear piston that slides longitudinally with a predetermined amplitude to define a metering chamber having a predetermined volume.

[0022] In contrast to the pumps described above in relation to the prior art, the single-acting pump of the present invention does not involve any rotation of the piston within the cylinder housing. The piston is only capable of reciprocating (sliding) movement. This mitigates shear friction induced by rotation around the cylinder axis, which can be detrimental when handling, for example, protein-containing products. Preferably, the pump does not have a dynamic seal between the cylinder and the piston.

[0023] The inlets and outlets are preferably arranged as nozzles protruding from the cylinder body to allow the screwing in of connecting lines, the nozzles having, for example, tubular portions to allow the assembly of such connecting lines.

[0024] In a preferred embodiment, the nozzles are arranged perpendicular to the axis of the cylinder. The nozzles may be contained in the same plane perpendicular to the axis of the cylinder. The nozzles may be aligned or arranged at an angle, for example, a 90° angle, between them.

[0025] If the nozzles are in the same plane, this means that the connecting lines extend vertically from the cylinder body, so when the pump is operated in a vertical position, they are horizontal.

[0026] The connecting lines in the kit of the present invention are made of a flexible material that allows the lines to be blocked when pinched. This means that the pump kit of the present invention is designed to operate by alternately preventing fluid movement in the connecting line fixed to the inlet (inlet line) and the connecting line fixed to the outlet (outlet line). This means that the kit does not have a check valve for operating the pump. The inlet and outlet located in the cylinder body are simply openings, not valves. This significantly reduces the risk of pump malfunction, which could result from valve blockage due to, for example, high viscosity or crystallization or damage to the valve elements.

[0027] The connecting lines are typically silicone-based tubes or hoses.

[0028] In a preferred embodiment, the cylinder body comprises at least two assembled parts which can be made of different materials: a cylinder head, in which the inlet and outlet are located, and a piston housing, in which the piston can slide and which are held together by a joining means.

[0029] The joining means may be a sanitary fitting to maintain proper pump sealing during operation and handling of the pump. Sanitary fittings are well known to those skilled in the art. Such fittings may include a joint placed between two parts to connect them and a clamp to hold the sections together. This may mean that the sections have a specific design incorporating a rim at the connection point. Other types of joining means may also exist.

[0030] In a preferred embodiment, the piston and cylinder housing (at least the piston housing portion of the cylinder body) are made of ceramic.

[0031] If the cylinder body comprises several parts, the cylinder head can be made of a plastic material, for example polypropylene, and the joining means can also be made of polypropylene, or any other suitable material.

[0032] The present invention also relates to a drive system adapted to operate the kit of the present invention, the drive system comprising: a movable arm adapted to engage a fixing means of a piston of the pump and to drive said piston to reciprocate within the cylinder body; - pinching means configured to alternately pinch the connecting lines fixed to the inlet and the connecting lines fixed to the outlet, The movable arm is synchronized with the pinching means so as to close the connecting line fixed to the outlet when the piston moves outside the cylinder body, and close the connecting line fixed to the inlet when the piston moves inside the cylinder body.

[0033] Pinching here is equivalent to squeezing or blocking by applying pressure to the line.

[0034] The pinching means can be any means known to those skilled in the art for occluding a tube or hose.

[0035] The drive system of the present invention may be a single device or machine, or may be different machines connected to a synchronization module.

[0036] The drive system of the present invention may further comprise fixing means for fixing the pump in a fixed position during operation.

[0037] These fixing means comprise at least means for fixing the cylinder body of the pump.

[0038] Advantageously, engagement of the pump within the fixing means allows simultaneous engagement or positioning of the fixing means of the piston relative to the drive arm, which may be accomplished by self-interlocking means or by the action of a further piston locking means.

[0039] In a particular embodiment of the invention, the fixing means is arranged to allow insertion of the cylinder body by movement along the axis of the cylinder body, but not by movement perpendicular to the axis of the cylinder body. As pumps are normally intended to be placed with the axis of the cylinder body in a vertical position, such an arrangement - positioning the pump slightly above its operating position with the inlet and outlet connecting lines positioned above the pinching valve; - making it possible to insert the pump into the fixing means by moving it downwards in a vertical movement inside the fixing means and engaging the inlet and outlet connecting lines with the respective pinching valve elements;

[0040] The pump cannot be pulled any further forward.

[0041] Abutment means may further be envisaged to position the pump at a predetermined height. Further fixing means may also be envisaged to improve locking of the pump in its operating position.

[0042] This configuration offers several advantages.

[0043] First, it allows the use of a simple gripper to place the pump in its operating configuration. Grippers are known in the field of pumps, as they allow the assembled piston to be maintained within the cylinder body. The gripper can be a simple clamp that releases the pump when pulled laterally. Since the pump cannot move laterally, operation is very simple.

[0044] The second advantage is that the connecting lines can be positioned inside the pinch valves before the pump is secured. The lines have some flexibility, which helps absorb stress during the vertical movement of the pump for securing, especially since both pinch valves are open during this step. Positioning the connecting lines is also made easier by using the grippers.

[0045] In a particular embodiment particularly suited for the arrangement and operation of the pump kit of the present invention, the pinch valve comprises a fixed vertical cylindrical pin and a movable vertical cylindrical pin, the movable vertical pin being arranged to move along an arc towards the fixed pin so that the flexible line (connecting line of the kit of the present invention) placed between both pins is pinched until it is completely occluded and then moves away from the fixed pin to unocclude the flexible line. This design, i.e. the fact that the pin is cylindrical and the movable pin moves along an arc, presents the advantage of reducing the stress applied to the tubing and reducing the risk of crushing effects.

[0046] The present invention will be better understood from the following detailed description taken in conjunction with the drawings. [Brief explanation of the drawings]

[0047] [Figure 1] 1 is a schematic diagram of a kit of the present invention. [Figure 2] FIG. 2 is an exploded perspective view of a pump for use in the kit of the present invention. [Figure 3] FIG. 3 is an assembled perspective view of the pump of FIG. 2. [Figure 4] FIG. 4 is a cutaway view of the pump of FIGS. 2 and 3. [Figure 5] 1 is a perspective view of the pump portion of the kit of the present invention in an operating position within the drive system of the present invention; FIG. [Figure 6] FIG. 1 is a perspective view of a pump of the kit of the present invention held by a gripper. [Figure 7] FIG. 6 is an enlarged view of a pinch valve of the system of FIG. 5. [Figure 8] FIG. 1 is a schematic diagram of a kit of the present invention comprising multiple pumps. DETAILED DESCRIPTION OF THE INVENTION

[0048] Referring to Figure 1, the kit of the present invention comprises a single-acting pump 1, an inlet connection line 2 fixed to the inlet 21 of the pump, and an outlet connection line 3 fixed to the outlet 31 of the pump. The connection lines 2 and 3 are tubes made of a flexible material, here for example, pharmaceutical grade silicone, which allows the lines to be blocked when pinched.

[0049] Here, the outlet connection line 3 is equipped with an end needle 4 for dispensing the liquid into the final container. This end needle is preferably inserted into a protective holster. A sterile connector 5 is also envisaged here at the end of the inlet connection line.

[0050] A needle is shown here as an example, and the outlet connection line may terminate in another dispensing means or a connector to a dispensing means installed in the facility.

[0051] Referring to FIGS. 2-3, in which like elements are numbered alike, the pump 10 of the kit has a piston 11 slidably disposed within a cylinder body 12 .

[0052] The cylinder body 12 here comprises two assembled parts: a cylinder head 13 in which the fluid inlet 21 and the fluid outlet 31 are arranged, and a piston housing 14 in which the piston can slide. The piston housing 14 has a larger diameter than the cylinder head 13, so that the piston cannot penetrate into the cylinder head. A sanitary fitting 15 comprising a clamp 151 and a joint 152 fixed with a zip tie (not shown) keeps both parts of the pump together.

[0053] The pump is here made of two materials, the piston 11 and piston housing being made of ceramic and the cylinder head being made of polypropylene.

[0054] The cylinder body has an axis AA'. Both the inlet 21 and the outlet 31 allow fluid communication between the outside of the cylinder and a metering chamber 16 inside the cylinder body. The metering chamber 16 is here further defined by the upper end of the piston 11 within the piston housing.

[0055] The inlet nozzle 21 and the outlet nozzle 31 are here arranged in a plane perpendicular to the axis AA', with an angle of approximately 90° between them.

[0056] The lower end of the piston 11 projects from the cylinder 14 and is provided with means of fastening to an external machine for driving the movement of the piston, these fastening means being here an annular recess 17 facing the end of the piston.

[0057] The piston housing 14 here has, over part of its height, a centrally facing annular recess 18. This recess may be useful for handling the pump and for fixing it in an operating position on a drive system.

[0058] This design allows the pump of the present invention to handle very small volumes of liquid. In fact, the volume of liquid dispensed with each stroke of the piston is determined by the amplitude of the piston's movement within the piston housing. The pump can be designed with very small internal diameters, allowing the dispensing of less than 0.1 mL, for example, 0.08 mL. It is important that the system is free of check valves, as check valves would not allow for consistent accuracy at such small volumes.

[0059] Although the kit of the present invention is suitable for installation in known drive systems with pinched valves, the applicant has further designed a specific system which includes a novel pinching means.

[0060] Referring to Figure 5, the kit of Figures 1 to 4 is mounted on a drive system 50 adapted to operate the kit of the invention, which comprises a movable arm 51 arranged to drive the reciprocating movement of the piston 11 within the piston housing of the cylinder body, and pinching means arranged to alternately pinch the inlet connection line 2 and the outlet connection line 3.

[0061] The drive system 50 further comprises fixing means 53 for fixing the pump in a fixed position during operation. These fixing means here comprise a holder 531 fixed on a stand 54. The holder has a hollow cylindrical portion for receiving or housing the pump's cylinder body, the AA' axis of the pump being intended to be aligned with the axis of the hollow cylinder. This hollow cylinder has a radial opening 532 that allows axial insertion of the pump. The radial opening 532 is designed to prevent lateral withdrawal of the placed pump. A hinged door 533 can at least partially close the radial opening, thereby preventing axial withdrawal of the pump from the housing. A rotary latch 534 is further envisaged for securing the door 533 in a closed position.

[0062] The piston 11 is also fixed to the drive arm. The end of the drive arm 51 also comprises a cylindrical receiving portion with a radial opening 511 into which the end of the piston is inserted. A rotation lock 512 can act to close the radial opening 511. The rotation lock is shaped to be complementary to the recess 17 of the piston so as to act as an abutment means in the locked position, thereby preventing unwanted vertical movement of the piston relative to the arm. This ensures optimal accuracy of volume delivery.

[0063] The two pinching systems 52 and 55 are arranged on the drive above the means for fixing the pump, here below a platform 56 which is also fixed on a stand 54 .

[0064] Pinch valve 52 is here for managing the fluid circulation in inlet line 2. It comprises a fixed vertical post 521 suspended from platform 56 and a movable vertical pin 522, here an upwardly pointing ergot 522 located at the end of a horizontal segment 523, the other end of which is fixed to a pivot 524 hanging from platform 56 and also connected to a motor (not shown). Pivot 524 drives rotation of pin 522 along an arc towards fixed post 521, thereby closing the line. The distance between pivot 524 and pin 522 on segment 523 when the valve is open is such that the inlet connecting line can be positioned between them on the segment.

[0065] Following the same principle, but with a slightly different design, the pinch valve 55 is now for managing the fluid circulation in the outlet line 3. It comprises a fixed vertical post 721 hanging from the platform 56, at the bottom of which extends a horizontal segment 723, at the end of which is an upwardly pointing ergot 722. A movable vertical post 724 hangs down to be discharged from the platform 56 around a pivot 725 connected to a motor (not shown). The pivot 725 drives the rotation of the pressing post 724 along an arc towards the fixed ergot 722, thereby blocking the line 3. The distance between the post 721 on the segment 723 and the ergot 722 when the valve is open is such that the outlet connecting line can be positioned between them on the segment.

[0066] Although pinch valves 52 and 55 are not identical here and have a particular design, those skilled in the art will understand that they may be similar, may be inverted, or any other suitable pinch valve may be used. One advantage of this particular design is that the connecting lines are supported by gravity without further fastening, thereby facilitating installation.

[0067] To place the pump in an operating position, a gripper 60 can be used as shown in Figure 6. Gripper 60 is a conventional gripper that includes a handle 61, a clamp 64 that grips the cylinder head of the pump, a clamp 66 that grips the piston housing, and an ergot 62 that prevents the piston from moving outside the piston housing.

[0068] The pump connection lines are not shown in Figures 2-6 for clarity, but are fixed to the pump in the kit.

[0069] The operator takes the pump by the connecting lines 2 and 3 and holds it in a generally vertical position. He moves the pump towards the drive system, passing the pump head between the two pinch valves 52 until the connecting lines 2 and 3 are respectively above the horizontal segments 523 of the valves. This movement also allows the pump cylinder body to be inserted into the retaining part 531 of the drive system, with the end of the piston 11 being partially positioned in or just above its housing in the drive arm.

[0070] The operator applies a vertical downward movement until the cylinder body 12 rests on the flat surface inside the radial opening 532 of the cylinder holding attachment 53. This also allows the end of the piston 11 to be fully inserted into its recess in the drive arm. The operator can then rotate the lock 512 to secure the piston 11 to the arm 51. With the pump secured laterally, the gripper can be removed by the operator with a horizontal pulling motion.

[0071] The operator can finally close the door 533 and lock it by rotating the latch 534. Advantageously, the door 533 has a shape complementary to the recess 18 in the cylinder body of the pump, which also locks the position of the pump body vertically.

[0072] The operator then simply places the needle end of the outlet line 3 where it should be and connects the inlet line 2 to a reservoir of product to be dispensed. The pump is ready to operate.

[0073] Both the movable arm and the pinching means are electrically driven. They need to operate in sync as known to those skilled in the art. When the piston moves out of the cylinder body, the pinch valve around the outlet connection valve 3 presses against the line, closing it, and the pinch valve around the inlet connection valve 2 opens, allowing liquid from the reservoir to enter the pump. When the piston moves up the cylinder body, the pinch valve around the outlet connection valve 3 opens, and the pinch valve around the inlet connection valve 2 presses against the line, closing it, allowing liquid to flow from the pump towards the dispensing needle.

[0074] 8, the kit of the present invention can also comprise several pumps in parallel, for example five single-acting pumps 81, each having an inlet connection line 82 fixed to the inlet of the pump and an outlet connection line 33 fixed to the outlet of the pump. The inlet connection lines 82 merge into a single line 86 upstream of the pumps at point 84.

[0075] A sterile connector 85 is also envisaged here at the end of the inlet connection line, where a surge bag 87 is further inserted onto the single line 86.

Claims

1. A kit comprising: a pump (1) in which a piston is slidably arranged within a cylinder body, said cylinder body being arranged with an inlet (21) and an outlet (31) both allowing fluid communication between the outside of said cylinder and a metering chamber inside said cylinder body (12), said metering chamber being further defined by one end of the piston being within said cylinder body, the other end of said piston (11) protruding from said cylinder body (12); - a connecting line fixed to said inlet (2), a connecting line fixed to said outlet (3), A kit, wherein the connecting line is made of a flexible material that allows the line to be occluded when pinched.

2. 2. A kit according to claim 1, wherein the connecting line fixed to the outlet (3) comprises an end needle (4), preferably inserted in a protective holster.

3. 3. The kit of claim 1 or 2, which is sterile and further comprises a sterile packaging into which it is inserted.

4. 4. A kit according to any one of claims 1 to 3, wherein the connecting line fixed to the inlet (2) comprises a sterile connector (5) for connecting the line to a bulk tank.

5. 5. The kit according to any one of claims 1 to 4, wherein the inlet (21) and the outlet (31) are arranged with a nozzle protruding from the cylinder body (12).

6. 6. The kit according to claim 5, wherein the nozzle is arranged perpendicular to, and preferably in the same plane as, the axis of the cylinder.

7. 7. The kit according to any one of claims 1 to 6, wherein the cylinder body (12) of the pump (1) comprises at least two assembled parts.

8. 8. A kit according to claim 7, wherein the two parts are a cylinder head (13) in which the inlet and the outlet are located, and a piston housing in which the piston is slidable and both parts are maintained together by joining means.

9. 9. The kit of claim 8, wherein the joining means is a sanitary fixture.

10. 10. A kit according to any one of the preceding claims, wherein the piston (11) and at least a part of the cylinder housing are made of ceramic.

11. 11. A kit according to any one of claims 1 to 10, comprising several pumps (1), each with an inlet connection line (2) and an outlet connection line (3), said inlet connection lines being arranged downstream of a single main inlet line.

12. A drive system (50) adapted to operate a kit according to any one of claims 1 to 11, comprising: a movable arm (51) adapted to hold the protruding end of the piston (11) of the pump (1) and to drive the reciprocating movement of the piston (11) within the cylinder body (12); - pinching means arranged to alternately pinch the connecting lines fixed to said inlet (2) and the connecting lines fixed to said outlet (3); a drive system, wherein the movable arm (51) is synchronized with the pinching means so as to close the connecting line fixed to the outlet (31) when the piston (11) moves outside the cylinder body (12) and close the connecting line fixed to the inlet (21) when the piston (11) moves inside the cylinder body (12).

13. 13. The drive system (50) of claim 12, further comprising fixing means for fixing the pump (1) in a fixed position during operation.

14. the fixing means being arranged to allow fixing of the cylinder body (12) during downward movement along the axis of the cylinder body (12); A drive system (50) according to any one of claims 12 or 13.

15. A drive machine (50) according to any one of claims 12 to 14, further comprising means for locking the piston (11) of the pump (1) to the movable arm (51).

16. 16. A drive machine (50) according to any one of claims 12 to 15, wherein the pinch valve (5) comprises a fixed vertical cylindrical pin and a movable vertical cylindrical pin (522), the movable vertical pin (522) being arranged to move along an arc towards the fixed pin so that a flexible line arranged between both pins is pinched until it is totally occluded and then moves away from the fixed pin to unocclude the flexible line.

17. 12. A method for placing a kit according to any one of claims 1 to 11 into an operational mode, comprising: - positioning said pump (1) slightly above its operating position and positioning said inlet and outlet connecting lines (2, 3) above said pinching valve (52); - moving said pump downwards in a vertical movement inside the fixing means to engage said inlet and outlet connection lines with their respective pinching valve (52) elements.

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