NZ542425A

NZ542425A - A method and device for distribution of a fluid

Info

Publication number: NZ542425A
Application number: NZ542425A
Authority: NZ
Inventors: Christian Neumann
Original assignee: Stedim Sa
Priority date: 2003-03-11
Filing date: 2004-03-05
Publication date: 2007-03-30
Also published as: FR2852259B1; NO20053652L; JP2006524126A; FR2852259A1; BRPI0408122A; CA2517898A1; NO20053652D0; US20060231139A1; CN1756523A; WO2004082829A3; KR20050107507A; MXPA05009672A; AU2004222541A1; WO2004082829A2; EP1608465A2

Abstract

A method and device for distributing a fluid are disclosed. A valve (1) has multiple inlets and outlets and is equipped with a check valve. Connected to the valve are: a fluid sampling and injecting device, such as a syringe (2); a gas (e.g. air) supply conduit; a supply conduit for the liquid to be distributed; and a discharge conduit (6). The method consists of drawing in the liquid to be distributed in order to transfer it to the sampling and injecting device (2), injecting the liquid into the discharge conduit (6), drawing off the gas in order to transfer it into the sampling and injecting device (2), and injecting the gas into the discharge conduit (6) in order to push the remaining liquid into the discharge conduit (6).

Description

542425 1 A METHOD AND DEVICE FOR DISTRIBUTION OF A FLUID The present invention relates to a method and disposable device for sampling and apportionment of liquid, in particular under sterile conditions.

In the fields in particular of food, medicine, pharmaceuticals or biotechnology, there is the problem of the repeated transfer of fluids in particular in a sterile manner, and apportionment of a reproducible, precisely measured volume.

Today, this type of operation is carried out by separate, successive actions which multiply the connection/disconnection operations. The multiplication of these connections/disconnections leads to a high risk of contamination, either by exposure to the air, or because of incorrect handling by the operator.

A standard application is, for example in parenteral nutrition, the preparation of batches of nutritive mixtures to be administered subsequently to the patient, from a certain number of stock solutions such as: a solution of amino acids, a glucose solution, a lipid emulsion, to which are added small volumes of complementary substrates such as trace elements, mineral salts and vitamins.

In paediatrics and neonatology in particular, the composition of these mixtures is varied from day to day as a function of the nutritive state of the patient and the need to ensure that he has a suitable calorie intake.

The need to vary this mixture from day to day does not allow the use of standard mixtures supplied by the pharmaceuticals industry, the composition of which does not vary by definition.

These mixtures must therefore be prepared in the hospital, under perfectly aseptic conditions. This operation is generally carried out on a laboratory table under a laminar air flow.

A standard application is, for example in biotechnology, the repeated taking of samples from a solution in cell culture, throughout this same culture which extends over several days. This repeated sampling makes it Intellectual property office of n.2. 2 8 NOV 2006 RECEIVED Office of nz."""' 2 6 OCT 200S 2 -RECEIVED possible to ensure counting of the cells in a given volume and thus to follow their growth curve, and even to carry out sterility tests on the samples taken in order to ensure the absence of any contamination.

According to the method stage, this operation is generally carried out either on a laboratory table, or under a laminar air flow, or in controlled production zone.

In cell therapy, cells potentialized by genetic engineering have to be apportioned and then cultured in multiple reproducible individual doses, for subsequent administration to the patient (autologous vaccine).

This apportionment requires the reproducibility of each of the doses and the transfer of the latter in sterile mode. This operation is generally carried out on a laboratory table, under a laminar air flow.

It would therefore be desirable to have a simple method which is easy to implement, for distribution and apportionment of a fluid, in particular under sterile conditions.

It is the object of the present invention to overcome or ameliorate one or more of the disadvantages of the prior art, or at least to provide a useful alternative.

In a first aspect, the present invention provides a method for distribution of a fluid, comprising the steps of: a) simultaneously connecting to a multiple inlet and outlet valve equipped with a non-return valve: - a fluid sampling and injection device such as a syringe - an inlet pipe for gas - an inlet pipe for liquid to be distributed, and - an outlet pipe, b) drawing of the liquid to be distributed in order to be transferred into the sampling and injection device, c) injecting the drawn off liquid into the outlet pipe, d) drawing off gas in order to be transferred into the sampling and injection device, e) injecting the drawn off gas into the outlet pipe in order to push the liquid remaining in the outlet pipe. the outlet pipe.

The multiple inlet and outlet valve equipped with a non-return valve is preferably arranged in order to let in the liquid to be distributed, to let it out towards the sampling and injection device, to let it in from the sampling and injection device without the [R:\L1BLL] 19124.doc:lzv 3 possibility of apportionment by the entry of the liquid to be distributed (effect of the nonreturn valve), to let it out towards the outlet pipe. Such non- return valves are well known. For example the valves marketed by the company Filtertek Inc (USA) under the name 3-way check valve can be mentioned.

The inlet pipe of liquid to be distributed is preferably connected to a container containing said liquid to be distributed. This container can be for example a bottle or a pouch. This liquid inlet pipe is preferably equipped with a valve allowing or not allowing communication between the container and said inlet.

The inlet pipe for liquid to be distributed is preferably connected to several 10 containers containing several liquids to be distributed and preferably to a container containing a rinsing liquid.

To this end, said liquid inlet pipe can be supplied by several supply tubes, each preferably being equipped with a valve.

The gas inlet pipe can preferably open directly into the multiple inlet and outlet valve.

The gas preferably originates from a branch pipe provided on the liquid inlet pipe. This branch pipe is itself also preferably equipped with a valve allowing or not allowing communication between the air intake and the liquid inlet pipe.

A filter, preferably a sterilising filter, is preferably provided on the gas inlet pipe. 20 The gas, for example the nitrogen or air coming from this pipe, is therefore sterile.

The fluid sampling and injection device can, for example, be a pump in particular a dosing pump, but is preferably a syringe.

The outlet pipe preferably opens into a collecting container such as flexible pouch and preferably to several collecting containers. To this end, said outlet pipe can 25 preferably be separated into several tubes, each being preferably equipped with a valve.

The collecting container is preferably pre-connected, i.e. the container preferably comprises connections allowing the direct mounting of said collecting container onto the outlet pipes(s).

A fraction of a single liquid to be distributed or a mixture of several fractions of 30 different liquids can preferably be collected.

This outlet pipe is preferably equipped with a branch leading to a waste container, equipped with a valve. In particular a rinsing fluid can thus preferably be eliminated.

The multiple inlet and outlet valve is preferably equipped with a pipe for a 35 rinsing liquid.

[R:\LIBLLJl9124.doc: Izv intellectual property office of n.2. 2 6 OCT 2006 Pimril#r-rN 4 However, the rinsing liquid can preferably be contained in one of the containers of liquid to be distributed. This avoids use of an additional inlet on the multiple inlet and outlet valve.

The multiple inlet valve is preferably connected by a pipe to a rinsing liquid, a 5 rinsing liquid is drawn off in order to be transferred into the sampling and injection device, and it is preferably injected into the outlet pipe in order to be transferred towards a waste-recovery container.

The inlet pipe for liquid to be distributed is preferably supplied for example by one or two, preferably three, and more preferably four or more, containers of liquid to 10 distributed.

The outlet pipe opens, for example, into one or two, preferably three, and more preferably four or more, collecting containers of the liquid or liquids distributed.

Apart from the multiple inlet and outlet valve, the other valves the function of which is to direct the flows of liquid and gas during the implementation of the method 15 can, for example, be taps or preferably reversible clamps.

The above liquid sampling and apportionment method is preferably implemented under sterile conditions, and more preferably, using disposable components.

In a second aspect, the present invention provides a device which can be used in a method as defined above, comprising a multiple inlet and outlet valve equipped with a 20 non-return valve, said multiple inlet and outlet valve being provided with: - an adapter for receiving the fluid sampling and injection device such as a syringe, - an inlet pipe for gas, - with an inlet pipe for liquid to be distributed, and 25 - an outlet pipe.

The above inlet pipe for liquid to be distributed preferably includes an adaptation system for cooperating, with a container containing a liquid to be distributed. This adaptation system can preferably be perforating, self-perforating, be screw or bayonet fitting, have aseptic connections etc.

The gas inlet pipe is preferably a branch from the inlet pipe for liquid to be distributed.

The inlet pipe for liquid to be distributed preferably comprises a shared section on the side of the multiple inlet and outlet valve and more preferably, a set of tubes for several containers containing a liquid to distributed. intellectual property office of n.z. 2 6 OCT 2006 [R:\LIFJLI-] 19124. doc: Izv IRECEIVEDI The gas inlet pipe is preferably connected onto the shared section of the inlet pipe for liquid to be distributed.

The outlet pipe preferably comprises a section on the side of the multiple inlet and outlet valve and moreover a set of tubes for several containers having to contain a liquid to be distributed.

The pipe towards the waste container is preferably connected onto the shared section of the outlet pipe.

In the case of a single stock solution, the inlet pipe is also preferably the supply tube, advantageously in a single piece.

The method for distributing a fluid, which is the subject of the present invention has very useful qualities. In a preferred form made from plastic, which is sterile and disposable: it minimizes the number of connections under aseptic conditions and therefore reduces the risk of contamination by contact with the operator; it implements the concept of the closed system, independent of the ambient air and therefore reduces the risk of bacterial contamination; it is disposable, thus eliminating any risk of cross-contamination, batch by batch; it allows the precise measurement of the volume sampled or transferred; it allows the reproducibility of the volume transferred.

These qualities justify the use of the method for distributing a fluid described above in the applications referred above.

The preferred embodiments for implementing the methods described above also apply to the other aspects of the invention referred to above, in particular to the devices for implementation of the methods.

The invention will be better understood with reference to the attached drawing (Figure 1) which is a diagrammatic representation of an example of an assembly of the invention with multiple inlets and outlets.

In Figure 1 it is possible to discern the central element of the method and device according to the invention, a valve 1 with multiple inlets and outlets equipped with a nonreturn valve. This non-return valve allows the introduction of the liquid drawn off into the rigid body of a syringe 2 and its transfer, without returning downstream, towards the apportionment line.

[R:\LlBLLJ19124.doc: lzv intellectual property office of n.2. 2 6 OCT 2006 6 It is then possible to discern from upstream to downstream in the circulation of the liquids: 1) Upstream, an inlet line with multiple tubes 3 provided for connecting to flasks, one or more pouches, a reactor or a tank, containing the stock solution or solutions to be filled (not represented). They join together into an inlet pipe 4 in the valve 1 with multiple inlets and outlets, and constitute a shared section. 2) The valve 1 with multiple inlets and outlets. 3) The syringe 2 - which may or may not be pre-connected - with a capacity for [R:\LIBLL] 19124.doc: !zv intellectual property office of n.z. 2 6 OCT 2006 .received example of 10 ml to 500 ml allowing the precise measurement (with a tolerance close to the measurement on the syringe body) of the volume drawn off. 4) Downstream, a distribution line with multiple tubes 5 allows the transfer and 5 apportionment of the fluid drawn off towards the collecting pouches. They join together into an outlet pipe 6 of the valve 1 with multiple inlets and outlets, which constitutes a shared section.

) One or more collecting pouches 7 pre-connected or not pre-connected to the distribution line, allowing the collection of the volumes of stock solutions transferred. 6) On the inlet line, upstream, a sterilizing hydrophobic filter 8 is pre-connected in a branch. Its function is to allow the introduction of filtered air into the device and to evacuate all of the dead volume of liquid which could remain there. The dead volume of this closed system being constant, purging it makes it possible to reproduce the drawing-off and transfer operation as many times as desired, in reproducible manner. 7) On the distribution line, downstream, a waste pouch 9 pre-connected to a branch, with a volume for example of 1 to 5 litres, makes it possible to collect either air, or part of the liquid transferred serving as rinsing liquid between each transfer, if necessary. 8) Reversible sealing clamps. On all the branches of the device, a reversible sealing clamp 10 is installed wherever necessary in order to direct the flow of liquid or air during use (10S means that the clamp is installed on an outlet tube, 10E that the clamp is installed on an inlet tube, 10F that the clamp is installed on the filter tube and 10R that the clamp is installed on the waste pouch tube).

The above device can be used according to the following method: 1) The clamp on the desired inlet line is opened, the desired volume of stock solution is drawn off by aspiration into the syringe 2, measuring this volume on the body of the syringe. 2) The clamp 10E on the inlet line is closed, the clamp 10S on the apportionment line is opened, the measured volume of stock solution is transferred into the 8 apportionment line as far as the collection pouch 7. 3) The clamp 10E on the inlet line is closed, the clamp 10F downstream of the hydrophobic filter 8 is opened, air is drawn through the filter 8, using the syringe 2. 4) The stock solution trapped in the dead volume is pushed by means of the filtered air introduced up to the apportionment line is emptied into the collection pouch 7.

) The clamp 10E on the inlet line is opened, a volume of stock solution is drawn into the syringe 2. 6) The clamp on the distribution line is closed, the clamp 10R of the waste pouch is opened, the volume of stock solution is transferred into the waste pouch 9, in order to rinse the pipes.

The above sequence is recommenced as many times as necessary in order to ensure the repeated and reproducible transfer of the 15 measured volume of stock solution.

As may be understood by a person skilled in the art, a device such as that above can be produced in modules from separate optionally multipurpose elements. In addition to the valve 1 with multiple inlets and outlets, pipes can be found which are equally suitable for the inlet and the outlet, 20 branched or not branched. For example the same type of branched pipes is equally suitable for mounting the filter and the waste pouch. Moreover a pipe suitable for the inlet and the outlet can be mounted on a piece provided with a set of channels allowing the same number of tubes to be mounted.

This is why a subject of the present Application is a fluid 25 distribution unit characterized in that it comprises a multiple inlet and outlet valve equipped with a non-return valve, said valve being equipped with a fluid sampling and injection device such as a syringe or an adapter such as a cone for attaching a syringe, and two pipes, one being equipped with a branch (Y-shaped pipe), or four 30 pipes and a branch end piece (3 pipes connected onto a branch end piece corresponding to a pipe equipped with a branch).

Claims

9 WE CLAIM:

1. A method for distribution of a fluid, comprising the steps of: a) simultaneously connecting to a multiple inlet and outlet valve equipped with a non-return valve: 5 - a fluid sampling and injection device, - a gas inlet pipe, - a liquid inlet pipe for liquid to be distributed, and - an outlet pipe, b) drawing off the liquid to be distributed in order to be transferred into the 10 sampling and injection device, c) injecting the drawn off liquid into the outlet pipe, d) drawing off gas in order to be transferred into the sampling and injection device, e) injecting the drawn off gas into the outlet pipe in order to push the 15 liquid remaining in the outlet pipe.

2. A method according to claim 1, wherein the liquid inlet pipe is connected to several containers containing several liquids to be distributed. 20

3. A method according to claim 1 or 2, wherein the liquid inlet pipe is connected to a container containing a rinsing liquid.

4. A method according to one of claims 1 to 3, wherein the liquid inlet pipe is supplied by several supply tubes, each being equipped with a valve. 25

5. A method according to one of claims 1 to 4, wherein the gas originates from a branch pipe provided on the liquid inlet pipe.

6. A method according to one of claims 1 to 5, wherein a filter is provided 30 on the gas inlet pipe.

7. A method according to one of claims 1 to 6, wherein the fluid sampling and injection device is a dosing pump or a syringe. [R:\LIBLL] 19124.doc:lzv intellectual property office of n.2. 2 6 OCT 2006 RECEIVED 10

8. A method according to one of claims 1 to 7, wherein the outlet pipe opens into one or more collecting containers.

9. A method according to one of claims 1 to 8, wherein the outlet pipe 5 separates into several tubes, each being equipped with a valve.

10. A method according to claim 8, wherein the collecting container(s) is pre-connected.

11. A method according to one of claims 1 to 10, wherein a mixture of several fractions of different liquids is collected.

12. A method according to one of claims 1 to 11, wherein the outlet pipe is equipped with a branch towards a waste container, equipped with a valve.

13. A method according to one of claims 1 to 12, wherein the multiple inlet valve is connected by a pipe to a rinsing liquid, a rinsing liquid is drawn off in order to be transferred into the sampling and injection device, and the drawn off rinsing liquid is injected into the outlet pipe in order to be transferred towards a waste-recovery container.

14. A method according to one of claims 1 to 8, wherein the inlet pipe for liquid to be distributed is supplied by at least three containers for liquid to be distributed.

15. A method according to one of claims 1 to 14, wherein the outlet pipe opens into at least three collecting containers of the liquid(s) distributed.

16. A method according to one of claims 1 to 15, implemented under sterile conditions. 30 17. A device which can be used in a method as defined in one of claims 1 to 16, comprising a multiple inlet and outlet valve equipped with a non-return valve, said multiple inlet and outlet valve being provided with: - an adapter for receiving the fluid sampling and injection device, - a gas inlet pipe, 35 - a liquid inlet pipe for liquid to be distributed, and

[R:\LIB LL] 19124.doc :lzv 15 20 intellectual property office of n.z. 2 6 OCT 2006 RECEIVFn - an outlet pipe. 11

18. A device according to claim 17, wherein the outlet pipe is equipped with a branch towards a waste container. pipe comprises an adaptation system for cooperating with a container containing a liquid to be distributed. 20. A device according to one of claims 17 to 19, wherein the liquid inlet pipe comprises a shared section on the side of the multiple inlet and outlet valve and a set of tubes for several containers containing a liquid to be distributed. 21. A device according to claim 20, wherein the gas inlet pipe is connected onto the shared section of the liquid inlet pipe. 22. A device according to one of claims 17 to 21, wherein the outlet pipe comprises a shared section on the side of the multiple inlet and outlet valve and a set of tubes for several containers having to contain the liquid distributed. 23. A method for distribution of a fluid, said method substantially as hereinbefore described with reference to the accompanying drawing. 24. A device which can be used in a method for distribution of a fluid, said device substantially as hereinbefore described with reference to the accompanying drawing.

19. A device according to one of claims 17 and 18, wherein the liquid inlet Stedim S.A. By the Attorneys for the Applicant SPRUSON & FERGUSON intellectual property office of n.z. 2 6 OCT 2006 RECEIVED