GB2190901A - Dispensing device - Google Patents

Abstract

A device for dispensing sterile fluid comprises a chamber (73) which is selectively, sealingly, connectible with one of a first (59) and a second receiving station, a fluid inlet pipe (37) contiguous with a bellows chamber (83), a nozzle (77) contiguous with the other end of the bellow chamber (83) and a valve means (85) housed therein. The nozzle is movable between a retracted position out of sealing contact with the receiving station and an extended position to dispense fluid to the receiving station. The nozzle is biased to the retracted position and movable to the extended position in response to a first predetermined pressure in the sterile fluid being dispensed, and the valve means is openable by a second predetermined fluid pressure, greater than the first predetermined fluid pressure. The receiving station (59) comprises a block within the neck (61) of a bag (1) to be filled is clamped. The chamber (73), nozzle (77) and accessible exterior of block (59) are sterilised by microwaves. <IMAGE>

Description

SPECIFICATION Dispensing device The present invention relates to apparatus for dispensation of fluid, and also to apparatus combining the sterilisation and dispensation offluid with a minimal risk of contamination.

Sterile solutions intended for medicinal purposes are currently prepared by one of two methods. These two methods are terminal heat sterilisation, and aseptic processing.

Terminal heatsterilisation involves the preparation ofthe solution which is then distributed into containers, from which it will be dispensed, via a suitable filtration system. The containers are then sealed, and the filled containers are sterilised by heating at a given temperature forthetime required to sterilise the containers and their contents. This process is relatively safe, because the heat sterilisation of the final product in the dispensing containers gives a very low risk of contamination of the product, and a high degree of assurance that when the product is issued for administration it is sterile. However, the process is limitedforseveral reasons. The container must be capable of withstanding the heat sterilisation process whilst maintaining its integrity throughout.Thus, resilient and therefore relatively expensive materials must be used in the manufacture of such containers. Many products requiring sterilisation for medicinal purposes are not suitable for such heat sterilisation processes, for example, because they are unstable at high temperatures maintained for relatively long periods. There further has to be careful choice ofthe container, in relation to the liquid which it is to hold, to ensure that deterioration of the solution during sterilisation will not occur due to interaction between the material ofthe solution and the material of the container at high temperature. Finally, the heat sterilisation of fluid products in their containers is a complex and expensive process, and by nature cannot be a continuous one. Thus, the containers of solution must be made up and sterilised in batches.

Aseptic processing involves passing the solution to be sterilised, via a steriiising filter, into a previously sterilised bulkcontainer, under relatively sterile conditions. The fluid is then distributed from the bulk container into the sterile distributing containers in a carefully controlled "aseptic" environment, so that the risk of losing sterility during the time when the product is exposed to the environment, i.e. the time between leaving the bulk container and being sealed in the dispensing container, is minimised. This process has an advantage over the process of terminal heat sterilisation, in that all types of container, solution, and combination of container and solution, can be used, because there is very u n I ikely to be degradation or deterioration due to heat.However, the container used must be amenable to manipulation during the aseptic filling process.

Advanced clean room technology is required to provide the necessary standards in the "aseptic" filling environment. For example, airwhich has been filtered to exclude microorganisms should be provided, at standard temperature and humidity, both in the cleanroom (where the aseptic transfer of liquid occurs) itself, and also, independently, atthe place where the original filling operation of the bulk container takes place. Special cleanroom clothing must be provided to protect the productfrom contamination spread by the operatives involved in the process. This clothing has to be washed, sterilised and double wrapped prior to its re-use.

Highly skilled personnel, who undergo regular training, must be provided, and the success of the filling operation is often largely dependent upon their expertise. All these factors increase the cost of such a technique, and the number ofvarious factors involved increases the number of errors that may occurs. Thus, the risk of contamination during aseptic processing is high, often about 1 non-sterile container in 1 0~3, that is 1 in 1000. The degree of assurance of sterility provided by the standard terminal heat sterilisation processes is at least 1,000 times better than the assurance of sterility provided by aseptic processing, that is, a risk of contamination of less than 1 in 1000,000.

According to the present invention there is provided a device for dispensing sterilefluid comprising (a) a chamber, which is selectively, sealingly, connectible with one of a first and a second receiving station, and (b) within said chamber, dispensing means, comprising a passage forfluid, said dispensing means being movable between a retracted position out of sealing contact with either of said receiving stations and an extended position to dispense fluid to said first or second receiving station, said dispensing means being biased to said retracted position and movable to said extended position in response to a first predetermined fluid pressure, and valve means, disposed in said passage, said valve means being openable by a second predetermined fluid pressure, greaterthan said first predetermined fluid pressure, and (c) means for sterilising said chamber and said dispensing means.

Preferably the first receiving station comprises a chamberfor holding at least part of a receptacle for the sterile fluid. Preferably the receptacle itself is sterile and most preferably is a sterile bag. The first receiving station may contain a sterile elongate neck of the receptacle. The first receiving station preferably includes means for maintaining the sterility of the receptacle, such as a sealing membrane across the entrance of the receiving station. This membrane may be punctured when the sterile end ofthe dispensing means is inserted into sealing contact with the first receiving station,thus maintaining the sterility of the receptacle at all times during the dispensing procedure. In a particular embodiment of the present invention, the sealing membrane is disposed across the entrance to the receptacle.

In one embodiment of the invention, the membrane is not punctured by the actual entrance of the dispensing means into the receiving station but only at the time of dispensation of the fluid, preferably by the action of the opening of the valve.

The sterility ofthe receptacle may be further ensured by sterilising the outside ofthe receptacle and sealing the fully sterile receptacle inside a larger, also sterile receptacle, e.g. a bag.

Both the receiving stations may be enclosed in a block. The dispensing chamber may move thus allowing the dispensing chamberto be selectively in sealing contactwith either receiving station. Each receiving station may be brought into sealing contactwith the dispensing chamber by either linear or rotational motion. Preferably the receiving station not in sealing contact with the dispensing chamber is sealed from the environment. The receiving station maybe positioned linearlyon a rectangular or circular blockface. It may be in the bore of a cylinder, functioning as a rotational valve arrangement, the movement being either linear or rotary.

The dispensing means may be moved from the retracted position to the extended position by means of a pressure-expandablechamberincorporated in the dispensing device. This is preferably an axially extendible chamber, such as a bellows chamber.

The valve means ofthe dispensing device is preferably a valve biased into the closed portion by the action of a spring,the force ofwhich spring is less than the force exerted upon the valve in the opposite direction by said second predetermined fluid pressure. Therefore at the second predetermined fluid pressure, the valve will be forced open againstthe action of the spring and thus allow passage of the fluid through the dispensing device. Most preferably, the valve is situated at the end ofthe dispensing means which comes into contact with the receiving station.In such a case if the first receiving station contains a receptacle which has a neck, through which filling takes place, across the open end of which neck is a sealing membrane, thevalve,when open, may project from the end of the dispensing means and thus may break the membrane and allow passage of fluid therethrough.

When the chamber is not sealingly connected to the second receiving station the second receiving station may be sealed by a piston biased to close the opening to the receiving station by the action of a spring. This spring exerts aforce in the direction of the opening to the second receiving station less than that exerted bythe sealing valve projecting from the end ofthe dispensing means. Thus, when the dispensing means is in contact with the second receiving station in this embodiment, the valve is forced from the end of the dispensing means by the second predetermined fluid pressure, and forces the sealing piston away from the opening to the second receiving station against the action of the sealing spring, thus opening the entrance to the second receiving station and allowing passage of fluid out of the dispensing device, and into the second receiving station.

Preferably the chamber, the end ofthe dispensing means protruding into the chamber, and those parts ofthe receiving stations in contact with the chamber, are all sterilised by means of a plasma. Preferably, this plasma is initiated by the use of microwaves.

Microwaves maygeneratethesterilising plasma, for example, by spontaneous breakdown in field strength, or by some of the electrons produced by a hot filament, inducing breakdown. More preferably, this plasma is maintained whilst the dispensing means moves into contact with one or other ofthe receiving stations, thus ensuring the sterility of the surroundings until sealing contact has been made.

Preferably, the interior ofthe passage forming part of the dispensing means is sterilised by passing a fluid ofsufficienttemperature through said dispensing means passage into the second receiving station for a time sufficient to sterilise the interior of the dispensing means, and preferably also the interior ofthe second receiving station. This fluid preferably comprises water, and the temperature to which it is heated is preferably above 1500 Centigrade.

Preferably, the dispensing device comprises a nozzle, the passage within which is sealed buy a sealing valve at the open end of the nozzle. More preferably, the nozzle, when not in use, is partially retracted from the chamber.

In one embodiment the dispensing device comprises a nozzle, in the open end of which is situated a poppetvalve opened by the second predetermined pressure, and a pressure-actuable expandable chamber activated bythefirst predetermined pressure.

The dispensing device of the present invention is activated by the pressure of the sterile fluid which it is to dispense. The fluid is forced into the device, thus increasing the pressure within the device. When the fluid pressure builds up to a first predetermined value, the dispensing means is forced, by the pressure, towards the receiving station, until it is in sealing contact with the receiving station. In this position,the increase in fluid pressure can no longer be relieved by movement ofthe dispensing device and thus the fluid pressure within the device continues to rise to a second predetermined value.

At this value, the valve within the dispensing means is forced open and fluid is forced out ofthe dispensing means by the fluid pressure. The dispensing means, the chamber in which they are positioned, and the exterior and accessible interior of the receiving station, are all sterilised, prior to use, with a plasma, and this sterilisation continues until the dispensing means and the receiving station are in sealing contact, thus preventing any possibility of contamination entering either the interior of the dispensing means or the fluid which it is to dispense.

Since, during dispensation, the device is positioned securely in sealing contact with the receiving station by a first predetermined pressure lowerthan the second predetermined pressure required to open the valve and allow fluid to leave the dispensing means, fluid cannotflowfrom the dispensing means unlessthe dispensing means is first in sealing contact with one of the receiving stations. Thus, when fluid is flowing into the receiving stationsthere is no access to the external environment.

Preferably, the receptacle receiving the sterile fluid is sealed before the sealing contact between the first receiving station and the dispensing means is broken.

The device ofthe present invention has a number of advantages over the existing devices:- For example, the liquid is sterilised prior to dispensation and there is therefore no need for sterilisation ofthe dispensed fluid within a receptacle. Thus, a receptacle of material, such as flexible plastics material, which would melt were it subjected to heat to sterilise the fluid within it, may be used with the device of the present invention. Although this advantage accrues, theoretically, from the aseptic technique currently used, the dispensation offluid in that technique necessitates the fluid being in direct contact with the air of a large, supposedly sterile environment.In the device of the present invention, the chamber is a small space, sealed from the exterior of the device, and thus the probability of this space being sterile, after sterilisation with a plasma, is greaterthan if the space was larger, for example, a cleanroom. Furthermore, thefluid being dispensed is protected by the device, from even this small environment, at all times during the dispensation process, thus further reducing the possibility of contamination of the fluid. Thus, with the present invention, any sterile fluid may be placed into a receptacle without limitation to receptacles made from materials which can be heatsterilised, butwith, at the very most, the same risk of contamination as in the present heat sterilisation technique.

According to the present invention, there is further provided an apparatus for sterilising and dispensing fluid, comprising a firstfluid inlet, a secondfluid inlet, means for selectively receiving the flow of fluid from eitheror both ofthefirstfluid inletorthe second fluid inlet, pumping means, fluid sterilising means, means for maintaining fluid pressure within the apparatus, de-aeration means, and a dispensing device according to the present invention.

Preferably the apparatus further comprises a heat exchangerto equilibriate the fluid temperature either side of the fluid sterilising means. Preferably it further comprises a fluid cooler between the fluid sterilising means and the dispensing device according to the present invention, The apparatus may also comprise composition sensors, positioned to detect the composition of the fluid flowing into the dispensing device.

Preferably, the pump means is an electric pump, and more preferably, it is a metering pump.

Preferably, the fluid steriliser is a heat steriliser.

In one embodiment of the present invention, the means for maintaining pressure and the de-aeration means are combined in a single pressurising reservoir and de-aerator. This may comprise a spring operated piston slidable in a chamber and acting upon the fluid in the reservoir to maintain pressure on the fluid in the pressurising reservoir and de-aerator, and therefore in the whole apparatus. In one embodiment, the piston includes a bore extending therethrough, said bore having a valve to allowthe escape of any gas collecting in the pressurising reservoir and de-aerator.

Preferably, the first fluid inlet is an inletforthefluid to be dispensed, and the second fluid inlet is an inlet for a second fluid; this fluid is preferably water.

Preferably, the means for directing fluid flowfrom eitherthefirstfluid inlet orthe second fluid inlet is a changeovervalve.

Preferably the apparatus is sterilised by the second fluid from the second fluid inlet. To sterilise the apparatus, this fluid is heated to a temperature and for a time sufficient to sterilise the apparatus.

Preferably, the fluid to be dispensed is medicinal, e.g. saline solution, and more preferably it is dispensed into a sterile receptacle, such as, for example, a sterile plastic bag. In such embodiments, the apparatus further comprises means for sealing the receptacle in a sterile manner, preferably when the dispensing means and first receiving station of the dispensing device are still in sealing contact. If the receptacle is a sterile plastics bag, it is preferred that the sealing means comprises meansforheat sealing said bag.

Preferably, the second receiving station may direct the flow of fluid either to a drain or back into the apparatus through a third fluid inlet positioned between the first two inlets and the pumping means.

The composition sensor may be further connected to printing means, forthe purpose of printing a detailed label (in response to a signal from the sensor) for the receptacle into which the fluid being measured is flowing. Such details includethe amount of fluid in the receptacle, and its composition. Alternatively, the receptacle may be labelled priorto filling independently of the sensor.

Prior to use the apparatus may be sterilised by heating the second fluid and passing it th rough the apparatus at a temperature and for a time sufficient to sterilise the apparatus. The second fluid is then replaced by the fluid to be dispensed, which is itself then sterilised by the fluid sterilising means. Once sterilised, thefluid is then dispensed as described above, the fluid pressure in the apparatus being raised to the first and second predetermined values by the pumping means.

The major advantages of this apparatus may include one or more ofthefollowing :- (1 ) the fluid being subjected to heat sterilisation for a shorter time than in the currently-used thermal sterilisation technique which is aided if a cooler is also present and therefore the fluid is less likely to deteriorate, (2) The fluid may be more rapidly heated bythe presence of a heat exchanger positioned before the sterilising means to warm fluid prior to sterilisation.

The apparatus is made sterile, and is then filled with sterile fluid at all times during the dispensation process, (3) The fluid is sealed from the external environment, thus preventing contamination, (4) Fluid pressure within the apparatus is maintained at a level slightly higherthan atmospheric, so that, if the integrity of the apparatus is breached at any point, the fluid will flow out and thus prevent contamination entering the apparatus, (5) When dispensation is actuallytaking place, the dispensing device is in sealing contact with the first receiving station and, with the fluid sterilising means and thus, as both the apparatus and the receptacle are, atthat point preferably sterile, it is possible to sterilisefluid and dispense it without access to the external environmentandthereforewithoutgreat riskofcontamination ofthefluid, (6) The receptacle may then be sealed while the integrity of the sterile fluid-pathway provided bythe apparatus is still intact, and thus the risk of contamination of the fluid within the receptacle is minimal, (7) The apparatus is flexible in its possible uses and is also suitable for small runs of differing composition as opposed to apparatuses for executing present methods, which are only used in large batch production, (8) The apparatus of the present invention is compact and does not require excessive maintainance, whilstthe apparatus used in the present methods require large plants and skilled operators.

The present invention sterilises individual quantities of fluid by a heat process immediately priorto filling. With reference to the printing/labelling referred to above, it is possible for thesensortocomputethe Fvalueforeachvolume being dispensed and to print this value either directly on to the container or as part of a print-outforthe operation ofthe apparatus over a period of time. In contrast thereto, conventional autoclaving (heat sterilisation) processes rely upon a time-temperature chart of the conditions with the autoclave.

An assembly of pipes, for example of stainless steel, can of course be sterilised by passage of water or an aqueous solution through them at a suitable temperature and for an appropriate time. This procedure has been carried out, for example at 1 350C for 3 minutes but in conventional systems it has only been done once, namelyatthestartof a batch run.

Therefore it has not previously been possible to guarantee complete sterility, so thatautoclaving afterfilling has been necessary. In the present invention however, the complete filling circuit, including the internal surfaces, is heat sterilized before every filling operation.

As referred to hereinabove, plasma may be used in the present invention for sterilisation. In the present invention it is desired to sterilise the diaphragm which seals an already sterile container priorto penetration bythefilling nozzle, the interior of which is heat sterilised and the surface of which is itself sterilised bythe plasma actually during the penetration of the membrane. Thus the outer surface, including the sealed filling nozzle, is sterilised before the seal is penetrated.

In known processes, a bag isfirstfilled and then sealed, as a separate operation after detaching it from thefilling head. Such a procedure meansthat the contents of the bag are exposed to the atmosphere with possible risk of microbial contamination. It has therefore again been necessary to autoclave afterfilling/sealing. However in the present invention, no such exposure can occur since the filling nozzle remains in sealed contact until the tube or neck of the bag is sealed by crimping/welding.

The two compartment outer wrapper for the sterile bag which is one feature of the present invention, providesforthe sealed filling tube to be maintained in a sterile environment until just before use thereby reducing the problem of microbiological contamination to a mini mum. Also the filling and sealing process leaves the second compartment in a sterile condition.

It is well recognized that it has been difficultto achieve the highly desirable sterility ofthe outer surfaces of containers for liquids such as intravenousfluids. In the autoclaving of such filled containers or bags, some vapour from the liquid diffuses either out of the bag itself orthrough the wall of the outer container, into the space therebetween. Such vapour condenses on the subsequent cooling and thereby obscures the contents of the bag. It has therefore been difficultto inspect the cooled, autoclaved bag visuallyfor particles, cloudiness or the like before use. Such a problem is overcome by means of the present invention.

The risk of contamination, using the apparatus of the present invention is, at worst, no greaterthan the risk of contamination inherent in the heat sterilization process currently used. Indeed, the risk of contamination appears to be even less, probably less than 1 in 1 06 as a result of the various factors taken into account in the present invention, particularly: (a) the sterility of the sealed container, (b) the sterility of the fluid to be dispensed, (c) the sterility of the exposed surfaces, especially the filling nozzle and thefillertube, (d) the operation of the filling nozzle.

The present invention will now be further described by way of example, with reference to the accompanying drawings, in which: Figure 1 shows schematically an apparatus according to one embodiment ofthe present invention, in a first position, Figure2shows, schematically,theapparatus of Figure 1, in a second position, Figure 3 shows a vertical cross-section of pressurising reservoir and de-aeratoras used in the apparatus ofthe present invention, Figure4shows a vertical cross-section of dispensing device according to one embodiment of the present invention in sealing contact with the elongate neck of a sterile receptacle.

Figure 5shows a vertical cross-section of a dispensing device according to the present invention, in a sealing contact with a second connecting means, in a closed position, Figure 6shows the dispensing device of Figure 5 in an open position.

Figure 1 shows, schematically, a system according to one embodiment of the present invention, for sterilising a liquid and introducing it, under sterile conditions, into a sterile container, in this case a sterile plastic bag 1. The system comprises a liquid-product inlet 3 and a water inlet 5, both of which lead into a first change-overvalve 7. The use ofthechange-overvalve 7 allows introduction of only one ofthe liquid-product and water into the system from their appropriate inlets 3,5. A metering pump9 isconnected bya pipe 11 tothefirst change-overvalve 7. The metering pump 9 is, in turn, connected to a second change-overvalve 13 by a pipe 15.Thesecond change-overvalve 13feeds, into pipe 17, liquid received from either pipe 15, which leads from metering pump 9, or from another pipe 19.

Pipe 17 leads to a steriliser 25 which comprises a tank 29 and a heater 31. A pipe leads from the steriliser 25 to a pressurising reservoir and de-aerator 33. The construction of the pressurising reservoir and de-aerator 33 is described in greater detail in connection with Figure 3.

A pipe 35 having recirculation pump 21 therein (see description of Figure 4 hereinafter) leads from the pressurising reservoir and de-aerator 33 and passes around part 23 ofthe pipe 17 sothatthe part 23 and that part 27 of pipe 35 which is disposed around pipe 17 are in heat exchange relationship such that liquid in the pipe 27 servesto warm the liquid in pipe 23 priorto entering the steriliser 25. The heat-exchange pipe 27 continues as pipe 37 which leads to nozzle block 39. Around pipe 37 is a cooler tube 41 and between the coolertube 41 and the nozzle block 39 are positioned composition sensors 43 which surround pipe 37 and extend into the interior of pipe 37. There is also a cylindrical sterilising cavity 73 (see description of Figure4 hereinafter).Controlling the cooler 41 is a variable flow valve 45. The pipe 37 is flexible and is notfully extended in the first position as shown in Figure 1.

Adjacent nozzle block 39 is a closure element or block 47. Disposed opposite nozzle block 39 is a connecting block 49, which comprises a connection port or space 53 leading to a pipe 51. The pipe 51 leads to a third change-over valve 55. This third change-overvalve 55 selectively directs fluid flow from pipe 51 into either drain pipe 57 or into pipe 19.

Pipe 19 in turn, leads to the second change-over valve 13 as stated above. Adjacent connecting block 49, on the opposite side from third change-over valve 55, is clamping block 59. Neck 61 of a bag 1 to befilled is clamped within theclamping block59.

With the apparatus in the position shown in Figure 1, a system circuit is defined comprising the circuit including pipe 17, steriliser 29, pressurising reservoir 33, pipe 37, nozzle block 39, connecting block 49, third change-over valve 55, pipe 19, second change-overvalve 13, and pipe 17.

A microwave generator 63 is provided with a wave guide 65, and gas e.g. argon, may be fed, via pipe 67, into wave guide 65from an argon cylinder 69. The flow of argon can be controlled by control valve 71.

Although not shown, wave guide 65, which is flexible, extends to the sterilising space 73 of nozzle block 39 to convey the microwaves thereto.

Blocks 47 and 39 are movable, as a unit, relative to a unit of blocks 49 and 59, from the first position shown in Figure 1 to a second position, as shown in Figure 2, in which block 39 is opposite clamping block 59, and block 47 is opposite connecting block 49. Blocks 47 and 39 move, ratherthan blocks 49 and 59. Between blocks 47 and 39, and blocks 49 and 59 are PTFE bearings 38,40 which seal the gaps between the two units of block 47,39 and 49,59.

When not in use, the system is in storage mode. In such a mode blocks 47 and 39 are in the position as shown in Figure 1.

Figure 3 shows a vertical cross-section through the pressurising reservoir and de-aerator 33 of Figures 1 and 2. The reservoir and de-aerator 33 comprises a thick-walled tubular stainless steel pressure vessel 93, in one end ofwhich are positioned an inlet nozzle 95 and an outlet nozzle 97. A piston 81 is slidable within the pressure vessel 93, and is biased towards the end containing nozzles 95 and 97 by means of a compression spring 99 extending between the piston and the end ofthe vessel remote from the nozzles 95 and 97. Two O-ring seals 101 and 103 are provided between the piston 81 and the inner wall of the vessel 93, the rings 101,103 which surround the piston 81, being located in annular grooves 105 and 107 respectively.Extending axiallythrough the middle of the piston 81 is a non-return valve 109, comprising a bore 111 extending through the piston 81, and including a frusto-conical valve seat 113, on which valve seat 113 is positioned a spherical valve member 115, held in place bya valve spring 116.

Excessive pressure on the lower side of the piston as shown in Figure3will movethevalve member115 against the force of the valve spring 116, offthe valve seat 113,thus allowing fluid flow around the valve member 115 from the lower side of the piston 81 as shown in Figure 3 to the upper side ofthe piston 81.

However, if the pressure is greater on the upper side ofthe piston 81, then upon the lower side ofthe piston 81 the valve bearing 1 will merely be forced against the valve seat 113, causing a tighter seal in the valve 109 than under normal conditions.

Contiguous with the outlet of the valve 109 on the upper side ofthe piston 81 is aflexible capillarytube 117. This capillary tube 117 extends to a second outlet nozzle 119, which is positioned at the opposite end ofthe pressurising reservoir and de-aerator 33 from the first outlet nozzle 97.

The pressurising reservoir and de-aerator33 has several functions. It acts as a reservoir with a variable capacity, thus allowing fluid volume changes within the circuit to be accommodated. An increase in volume of liquid in the circuit will cause the pressure within the ci rcuit to increase, and this will force the piston 81 towards the second outlet nozzle 119, compressing the spring 99. The spring 99, forcing the piston 81 towards the inlet nozzle 95 and the outlet nozzle 97, causes pressure within the circuit at all times. Thus, even when the system is at storage temperature (about 2" Centigrade) and storage volume, the pressure within the circuit is maintained at a level higher than atmospheric (PO)- The device 33 also acts as a de-aerator. When the heater 31 raises the temperature in the system, the increase in the temperature of the liquid within the cylinder 93 causes the gas dissolved within the liquid to come out ofsolution. The gas bubbles thus formed, rise and coalesce around the valve 109, until the pressure ofthe airgathered aroundvalve bearing 115is sufficient to force the valve member 115 away from the valve seat 113 towards second outlet nozzle 119.

The gas escapes through the gap between the valve bearing 115 and outlet valve seat 113, via the capillarytube 117 and out of the outlet nozzle 119.

This de-aeration occurs during the sterilising cycle (see later description) when the temperature ofthe liquid risesto 1 50"C. Because ofthe high temperature, some superheated steam may also coalesce with the air around the non-return valve 109. Any superheated steam which may leavethe pressurising reservoir and de-aerator by means of valve 109, condense in capillarytube 117 and run backto the valve 109 will not re-enter the pressurising reservoir since the valve is one-way and onlyopenswhenthe pressure is sufficientto blow away such condensed steam.No bubbles are carried in the liquid flow through the outlet nozzle 97, as the downward transit time for liquid from the reservoir to the outlet nozzle 97 is greaterthan the upward drift rate, and thus bubbles will tend to move towards the non-return valve 109. The outlet nozzle 97 has a large diameter to reduce outflow velocity.

Figure 4 shows a detailed section through the nozzle block 39 in a second position, adjacent the clamping block 59. The nozzle block 39 comprises the pipe 37, through which liquid product enters the block, and which connects with bellows 83 contained in a bellows cavity 121. Contiguous with the bellows 83 is an elongate outer member 76 of a nozzle 77. The outer member 76 has a frusto-conical sealing face 78 and the nozzle is constrained to move longitudinally in the nozzle block 39 by a cylindrical polytetrafluoroethylene (PTFE) bearing 122. The nozzle 77 extends into a cylindrical sterilising cavity 73. The nozzle further comprises a valve stem 85, which is able to move longitudinally within the elongate member76 by virtue of annular bearings 123 and 125.A spring 89 is disposed around the valve stem 85 between one face of the bearing 125 and a thickened end 84 of valve stem 85.

Atthe opposite end of the valve stem 85 to the thickened end 84, the valve stem is widened at 133 to provide a valve head which is biased by the spring 89 into sealing engagement with a frusto-conical valve seat 87 formed on the outer member 76 of the nozzle 77.

The clamping block 59 comprises a conventional heat sealer and cropper mechanism 91 and a cylindrical adaptor cavity 127 which, in the position shown in Figure 4, is open to sterilising cavity 73 of nozzle block 39. A neck groove extends from the adaptor cavity 127 to a bag cavity 129 (see Figures 1 and 2). In operation a sterile bag 1 is positioned in the bag cavity 129 with neck 61 in the neck groove. A filling-tube adaptor 131 is disposed within the bag neck 61 and produces a widened section in the bag neck 61 within the adaptor cavity 127. Across the open end of the filling-tube adaptor 131 is a sealing membrane, (not shown), which ensures the sterility of the inside of the sterile bag 1 and the bag neck 61 atthestartofthefilling operation.

In Figure4the nozzle 77 is shown in use, filling a bag 1 with liquid-product, as will be described. When the nozzle 77 is not in use, i.e., when the pressure in the system is low, the bellows are contracted, and the whole nozzle 77 retracts towards pipe 37 and out ofthe sterilising cavity 73. Also, the spring 89 acting againststem end 84forcesvalvestem 85 against valve seat 87 thus sealing the nozzle 77. In this condition the nozzle 77 is both closed and retracted.

When the nozzle 77 is to be used, the pressure in the circuit is caused to increaseto a predetermined value P1. This pressure expands the bellows 83 to theirfull extent, thereby moving the nozzle 77 to the left, as shown in Figure 4, into the sterilising cavity 73. In this intermediate position the nozzle 77 is in sealing contact with the entrance of the filling-tube adaptor 131, within the adaptor cavity 127, with the sealing member having been ruptured bythe widened valve head 133 of the stem 85.

Atthe same time as the bellows 83 are expanding, a plasma generated by microwave generator 63 is conveyed by wave guides 65to sterilising cavity 73, sterilising the cavity 73, the nozzle 77 and the accessible exterior of the opposite block 59. The generator 63 is stopped when the nozzle 77 is in place.

Increasing the pressure within the circuit by either metering pump 9 or recirculation pump2l,ora combination of both, to a value P2, which is higher than P1, causes the force exerted on the stem end 84 towards the valve seat 87 to be greater than the force ofthe spring 89 on the stem end 84 away from the valve seat 87. Thus the stem end 84 is forced towards the valve seat 87 of the outer member 76 againstthe force of spring 89, compressing spring 89. The valve 133/87 is thus opened, allowing fluid flowthrough the nozzle 77 and into the bag 1.

When the filling operation is complete, the metering pump 9, or recirculation pump 21,or both, are turned off and the pressure within the circuitfalls to a value P1. This pressure exerts a force upon the stem end 84 which is less than the force in the opposite direction exerted by the compressed spring 89, and the valve 133/87 closes, thereby preventing furtherfluid flowthrough the nozzle 77. As the pressure in the circuit falls still furtherto a value below that required to expand the bellows 83, the bellows 83 contract, thus pulling the nozzle 77 through the PTFE bearing 122 and towardsthe bellows cavity 121.Thus, before use, the nozzle 77 must be sterilised as it is extended into the sterilising cavity 73 to sterilise those parts of the nozzle 77 which are covered by the PTFE bearing 122 when the nozzle 77 is not in use. It should be noted thatthe nozzle77 will only open tofluid flow, (by means of moving the head 133 ofthe valve stem 85 of the valve seat 87) once the nozzle 77 is in sealing engagement with the filling-tube adaptor 131 of the neck 61 ofthe sterile bag 1. This ensures that no contamination can enter the nozzle 77, and thus the sterilisation circuit, from outside the nozzle 77, the circuit, orthesterile bag 1, except, possibly, via the sterilising cavity 73, which is thus sterilised before and after use, with plasma, to prevent such contamination.

Operation ofthe nozzle 77 when the nozzle block 39 is opposite the connecting block 49 is similarto that described above and Figure 5shows, schematically, the nozzle 77 in the intermediate position (i.e. with the valve 133/87 in closed position but with the nozzle extended) with the end of the nozzle 77 within the connecting block 49. In this position, the pressure in the circuit is such thatthe bellows 83 have expanded, extending the nozzle 77 into sealing contact with the connecting block 49, but the pressure is notsufficienttoforcethe head 133 of the valve stem 85 from valve seat 87, and thus the nozzle 77 is not open for flow of fluid therethrough.

A sealing ring 137 provides a seal between the nozzle 77 and the connecting block49. A piston 139 is slidablymountedto an annularPTFE bearing 141 within the connecting block 49, the bearing 141 allowing movement of the piston 139 laterally within connecting space 53. Within the piston 139 is a spring 143 which biases the piston 139 to the right as shown in Figure 5, forcing the face 147 of the piston 139 against a shoulder 145 defining one end ofthe connecting space 53. In this position the interior of the connecting space 53 is sealed from the exterior by the sealing O-ring 135 positioned around the end face 147 of the piston 139. The end face 147 of piston 139 has a conical recess 149, which is contiguous with an entrance 151 to the connecting space 53 formed in the end wall of the connecting block 49.

The conical opening formed by the entrance 151 to the connecting space 53 and the conical recess 149 receives the conical end of the nozzle 77 comprising the frusto-conical face 78 of the outer member 76, and the valve head 133.

When the pressure in the circuit rises above a predetermined level P2 the stem end 84 is moved againsttheforce of spring 89, thus forcing valve stem head 133 away from valve seat 87 and opening the valve 133/87. This causes the piston 139 to be moved to the left, as shown in Figure 5 againstthe force of spring 1 43. This will allowflowoffluidfrom the interior of the nozzle 77, through the valve 133/87 into the connecting space 53, and through connecting space 53, between the piston 139 and the block 49, around the PTFE bearing 141, into pipe 51 (see Figure 1). This position, with the nozzle 77 open and the piston 139 forced back into connecting space 53 against the force of spring 143 is shown in Figure 6.

When nozzle 77 is sealed and withdrawn towards the bellows cavity 121, the interior of the connecting space 53 is sealed from the exterior of block 49 by the sealing O-ring 135forming aseal betweentheend 149 of piston 139 and the end 147 of the connecting space 53. When the nozzle 77 is in sealing contact with block 49 and is open to fluid flow through the nozzle 77 and into the connecting space 53, theflow is uncontaminated because the connection between the nozzle 77 and block49 is sealed by the action of O-ring 137.

The circuit, in storage mode, is filled with sterile water. Argon gas is bled from cylinder 69 through pipes 67 and 65 into the sterilising space 73, thus maintaining the sterility of the sterilising space 73.

The pressure of the sterile water in the circuit is slightly higher than atmospheric and is defined as PO.

There is no circulation ofwaterthrough the system as nozzle 77 is retracted into bellows cavity 121, away from connecting space 53, and thus there is a break in the circuit between the sealed nozzle 77 and the sealed connecting space 53.

At the start of the operation the nozzle block 39 is adjacent and in sealing contact with the connecting block49. To prepare the system for use, the heater 31 is activated. This heats the water in the circuit. As the heated water expands into the pressure vessel 93 of the pressurising reservoir and de-aerator33, it forces the piston 81 away from inlet nozzle 95 and increases the pressure in the circuit to a value P1, higherthan PO the resting pressure. This pressure P1 expands the bellows 83 in nozzle block 39. This expansion of the bellows 83 moves the nozzle 77 into the sterilizing space 73 and sealingly engages the nozzle 77 with the connecting space 53 in block 49, as shown in Figure 5.When the nozzle 77 is so engaged, the recirculation pump 21 is activated in orderto increase the pressure to a value P2, opening the nozzle 77 allowing water to be pumped round the, now, completed circuit. The action ofthe recirculation pump 21 further increases the pressure in the system to a value Pd22. This pressure opens the valve 133/87 and thus allows the water to flow around the circuit, driven by the recirculation pump 21. The temperature of the water increases to 1500 Centigrade, and is kept at that temperature for such time as is necessary to sterilise the entire circuit. The heater is then switched off and the water cools.

Once the circuit has been sterilised, it is flushed, that is to say, liquid-product is pumped into the system by switching of change-overvalve 7, and displaces the sterile water. The heater 31 is turned on as isthe pump 21. The metering pump 9 pumps the product into the system and the product displaces the sterile water, which is pushed through the system into the third change-overvalve 55 which is adjusted to directthe water into the drain pipe 57 and thence to waste. The cooler 41 is put into operation and is controlled by the variable flow valve 45to maintainthetemperatureoftheliquidpassing through the nozzle block 39 at 95" Centigrade.Once the volume of product that has been delivered by the metering pump 9 exceeds the system volume, the second change-overvalve 13 is switched so that it directsflowfrom pipe 19to pipe 17, and the third change-overvalve 55 is also switched so that it directs flow from pipe 51 into pipe 19, thus recompleting the circuit. During this stage, an operator places the neck 61 of a sterile bag 1 into clamping block 59, and the bag 1 into the bag cavity 129.

The liquid-product in the circuit is then sterilised.

Recirculation pump 21 circulates the liquid-product around the circuit and the heater 31 heats the liquid-productto 1500 Centigrade for such time as is sufficientto sterilise the liquid without degrading the liquid-product. During this stage, the cooler 41 is not in operation. During the heating of the liquid-product by heater 31 the liquid-product de-aerates, and the escaping air, together with superheated steam, is released from the pressurising reservoir and de-aerator 33 via outlet 119. As soon as the time required to sterilise the liquid-product has elapased, the heater31 is turned off and the cooler 41 is activated. The variable flow valve A5 controls the operation of the cooler 41 to cool the fluid in the circuit to 950 Centigrade. The recirculation pump is then turned on and the pressure in the ci rcuit falls to P1, at which point valve 133/87 is closed by the action ofthe spring 89.

The pressure then falls steadilyto the value P,, which is slightly greater than atmospheric, as the temperature in the circuit falls correspondingly. This pressure drop causes the bellows 83 to contract, thereby withdrawing the nozzle77fromthe connecting space 53 of block49. Blocks 47 and 39 are then moved into the second position in which block 39 is opposite to block 61 and block 47 is opposite block 49, sealing the connecting space 53. This second position is the filling position.

The filling stagethen commences. The sterilising cavity 73 is first purged with argon from the argon cylinder 69. The microwave generator 63 is then activated, and the resulting microwaves produce a plasma in the filling cavity 73. This plasma sterilises the filling nozzle 77 and the membrane covering the bag neck 61. Once the exposed surfaces ofthefilling cavity 73 and the exterior of the clamping block 61 have been sterilised, the metering pump 9 is turned on and the second change-overvalve 13 is switched to connect pipe 15 with pipe 17. This causes liquid-product to be pumped into the circuit, thus raising the pressure in the circuitto a value P1.This increased pressure expands bellows 83 which move the nozzle 77 into sealing contact with the fil I i ng-tu be adaptor 131, breaking the sealing membrane (not shown), which is stretched across the open end of the filling-tube adaptor 131 in the neck 61 ofthe sterile bag 1. At this point the microwave generator 63 isturned off. The metering pump 9 continues to pump liquid-product into the circuit, thereby raising the pressure still furtherto the value P2. This pressu re is sufficient to force the stem end 84 of the valve stem 85, in the nozzle 77, towards the open end ofthe nozzle 77, against the force of the spring 89, thus opening the valve 133/87.Sterilised liquid-product isforced from the system, through the nozzle 77 bythe pressure of new unsterilised liquid being pumped by metering pump 9 into the steriliser 25, dispiacing the sterile liquid in the system. The sterile fluid flows through nozzle 77 into the neck 61 of the sterile bag 1 and then into the bag 1. The temperature of the sterile liquid flowing from the steriliser 25 into the bag 1 is controlled by the cooler 41.The sensors 43 check the composition ofthe liquid. As the metering pump 9 pumps liquid around the system at a specific rate, the pump 9 is automaticallyturned off after sufficient time has passed forthe sterile bag 1 to have been filled with sterile product-liquid. The second change-overvalve 13 isthen switchedto connect pipes 19 and 17.

The heat sealer 91 is then activated. This seals the neck61 ofthesterilebag 1 andseverstheneck61 ata pointtothesideofthenewlyformed heatseal nearestthe nozzle 77. Once the neck 61 has been sealed, the recirculating pump 21 is deactivated and the pressure in the system falls. Thisfall in pressure first causes valve 133/87 to close and then allows the bellows 83to contract,thus causing the nozzle 77to bewithdrawn from the clamping block 59. The blocks 39 and 47 are then moved to the first position where the nozzle 77 is aligned with the connecting space 53 of block 49. The bag 1, now full and sealed, is removed and the remainder of the neck 61 is removed from the clamping block 59.The sensors 43 feed the information of the composition ofthe liquid-product being dispensed into a computer and printer (not shown), which prints the information onto a label for the bag 1.The label is then affixed to the bag 1. A new sterile bag 1 is then placed with its neck 61 in the clamping block 59 and the cycle returnsto the stage of sterilising the circuit (stage 3).

Once the final sterile bag 1 has been filled with liquid-product, the system is shut down. The blocks 47 and 39 are moved to the first position, where block 39 is opposite block 49. The second change-over valve 13 is adjusted to direct the liquid flow from pipe 15 into pipe 17, the first change-overvalve 7 is adjusted so that water flows from pipe 5 into pipe 11, and the third change-over valve 55 is adjusted so that liquid flows from pipe 51 into drain pipe 57. The metering pump 9 is then activated, and sterile water is pumped through the system, displacing liquid-product in th system, so that the liquid-product is flushed from the system and out of drain pipe 57.When the delivered volume of sterile water has exceeded the volume of the circuit, the second change-overvalve 13 is adjusted to direct fluidflowfrom pipe 19to pipe 17,thethird change-overvalve 55 is adjusted to direct fluid flow from pipe 51 into pipe 19, thus completing the circuit within the system, and the metering pump 9 is de-activated. The heater 31 is then switched on so that the temperature of the water in the circuit increases to 1500 Centigrade. At the same time the sterile water is circulated by means of the pump 21.

This process continuesforthe calculated time required to sterilise the water in the circuit. The heater31 and the pump 21 are then turned off. Asthe fluid cools, the piston 81 in the presurising reservoir and de-aerator 33 is pushed towards the inlet nozzle 95 (as shown in Figure 3). In this state the system is in storage mode as described above.

The pressure in the system in storage will equilibriate ata value PO P0 isslighly higherthan atmospheric pressure, but it is not high enough to expand the bellows 83, and thus to cause the nozzle 77 to extend into the sterilising space 73, and thus it is not high enough to cause the nozzle 77 to open.

When the circuit is not in use, thefactthatthe pressure P0 within the circuit is slightly higherthan atmospheric allows an automatic checkto take place beforethesystem is used again, in that, if pressure in the circuit has fallen below the va lue P,, it is an indication that circuit integrity has not been maintained.

Claims (42)

1. A device for dispensing sterile fluid comprising a chamber, which is selectively, sealingly, connectible with one of a first and a second receiving station, and within said chamber, dispensing means, comprising a passage for fluid, said dispensing means being movable between a retracted position out of sealing contact with either of said receiving stations and an extended position to dispense fluid to said first or second receiving station, said dispensing means being biased to said retracted position and movable to said extended position in response to a first predetermined fluid pressure, and valve means, disposed in said passage, said valve means being openable by a second predetermined fluid pressure, greaterthan said first predetermined fluid pressure, and meansforsterilising said chamber and said dispensing means.

2. A device for dispensing sterile fluid as claimed in claim 1, wherein said first receiving station comprises a chamberfor holding at least part of a receptacle for the sterile fluid, which receptacle itself is sterile and comprises a sterile bag, said first receiving station is capable of containing a sterile elongate neck of said receptacle and includes means for maintaining the sterility ofthe receptacle comprising a sealing membrane, said membrane being punctured when the sterile end of said dispensing means is inserted into sealing contact with said first receiving station, thereby maintaining the sterility of the receptacle at all times during the dispensing procedure.

3. A device as claimed in claim 2, wherein the sealing membrane is disposed across the entrance to the receptacle.

4. A device as claimed in claim 2 or claim 3, wherein said membrane is not punctured by the actual entrance of said dispensing means into said first receiving station but is punctured only at the time of dispensation of said sterile fluid by the action ofthe opening of said valve means.

5. A device as claimed in any one of claims 2 to 4, wherein the outside of said receptacle is sterilised and the fully sterile receptacle is sealed inside a larger, also sterile receptacle.

6. A device as claimed in any one of the preceding claims, wherein both said receiving stations are enclosed in a block and said dispensing chamber is movable to thus allow a selectively, sealing contact with eitherofsaid receiving stations, each of said receiving stations being brought into sealing contact with said dispensing chamber by either linear or rotational motion and the receiving station not in sealing contactwith said dispensing chamber is sealed from the environment.

7. A device as claimed in any one of the preceding claims, wherein the dispensing means is movable from said retracted position to said extended position by means of a pressure-expandablechamberincorporated in said dispensing device.

8. A device as claimed in claim 7, wherein said pressure-expandable chamber comprises a bellows chamber.

9. Adeviceasclaimed in any one ofthe preceding claims, wherein said valve means of said dispensing device comprises a valve biased into a closed position by the action of a spring, the force of which spring is less than the force exerted upon the valve in the opposite direction by said second predetermined fluid pressure.

10. Adevice as claimed in anyoneofthe preceding claims, wherein said valve is situated at the end of said dispensing means which comes into contact with said first receiving station.

11. A device as claimed in any one of the preceding claims, wherein said first receiving station contains a receptacle which has a neck, through which filling takes place, across the open end of which neck is a sealing membrane, the valve, when open, projects from the end of said dispensing means and thereby breaks the membrane and allows passage of fluid therethrough.

12. A device as claimed in any one of the preceding claims, wherein when said chamber is not sealingly connected to the second receiving station said second receiving station may be sealed buy a piston biased to close the opening to said second receiving station by the action of a spring, which spring exerts a force in the direction ofthe opening to said second receiving station less than that exerted by slid sealing valve projecting from the end of said dispensing means.

13. A device as claimed in any one of the preceding claims, wherein said chamber, the end of said dispensing means protruding into said chamber, and those parts of said receiving stations in contact with said chamber, are all sterilised by means of a plasma.

14. A device as claimed in claim 13, wherein said plasma is initiated by the use of microwaves.

15. Adevice as claimed in claim 13 orclaim 14, wherein said plasma is maintained whilst said dispensing means moves into contact with one or other of said receiving stations.

16. A device as claimed in any one of the preceding claims, wherein the interior of said passageforming partofsaid dispensing means is sterilised by passing a fluid ofsufficienttemperature through said dispensing means passage into said second receiving station for a time sufficient to sterilise said interior of said dispensing means, and also sterilise the interior of said second receiving station.

17. A device as claimed in claim 16, wherein said fluid comprises water, which is heated to above 1500 Centigrade.

18. Adeviceasclaimed inanyofthepreceding claims, wherein said dispensing device comprises a nozzle, the passage within which is sealed by a sealing valve at the open end of the nozzle, which when not in use, is partially retracted from the chamber.

19. A device for dispensing sterile fluid comprising a first fluid inlet, a second fluid inlet, means for selectively receiving the flow offluid from either or both of the first fluid inletorthesecondfluid inlet, pumping means,fluid sterilising means, means for maintaining fluid pressure within the apparatus, de-aeration means, and a dispensing device as claimed in any one of the preceding claims.

20. A device as claimed in claim 19, wherein the apparatus further comprises a heat exchanger to equilibriate the fluid temperature either side of said fluid sterilising means and a fluid cooler between said fluid sterilising means and said dispensing device.

21. A device as claimed in claim 19 or claim 20, wherein said apparatus also comprises composition sensors, positioned to detect the composition ofthe fluid flowing into said dispensing device.

22. Adevice as claimed in anyone of claims 19to 21,wherein said pump means comprises an electric metering pump.

23. A device as claimed in any one of claims 19 to 22, wherein said fluid steriliser comprises a heat steriliser.

24. Adevice as claimed in any one of claims 19to 23, wherein said means for maintaining pressure and said de-aeration means are combined in a single pressurising reservoir and de-aeratorwhich comprises a spring operated piston slidable in a chamber and acting upon said fluid in said reservoir to maintain pressure on said fluid in said pressurising reservoirand de-aerator, and in the whole apparatus.

25. A device as claimed in claim 24, wherein said piston includes a bore extending therethrough, said bore having a valve to allowthe escape of any gas collecting in said pressurising reservoir and de-aerator.

26. Adevice as claimed in anyone of claims 19to 25, wherein saidfirstfluid inlet is an inletforsaid fluid to be dispensed, and said second fluid inlet is an inlet for a second fluid, said second fluid being water and the means for directing fluid flow from either said first fluid inlet or said second fluid inlet is a changeover valve.

27. Adeviceas claimed in any one of claims 19to 26, wherein said apparatus is sterilised by said second fluid from said second fluid inlet, which fluid is heated to a predetermined temperature for a time sufficienttosterilisesaid apparatus.

28. A device as claimed in any one of claims 19to 27, wherein said sterile fluid is dispensed into a sterile receptacle comprising a sterile plastic bag.

29. A device as claimed in claim 28, further comprising means for sealing said receptacle in a sterile manner when said dispensing means and first receiving station of said dispensing device are still in sealing contact.

30. A device as claimed in any one of claims 19to 29, wherein said second receiving station directs the flow of said fluid either to a drain or back into said apparatus through a third fluid inlet positioned between said first two inlets and said pumping means.

31. A device as claimed in any one of claims 21 to 30, wherein said composition sensor is connected to printing means, forthe purpose of printing a detailed label for said receptacle into which said fluid being measured is flowing.

32. A nozzle for dispensing fluid comprising an elongate outer member, valve means and biasing means such thatthe valve is biased into a closed position and openable in response to predetermined fluid pressure within said nozzle.

33. A nozzle as claimed in claim 32, wherein said valve means is disposed at the dispensing end of said elongate outer member and is movable longitudinally within said elongate outer member.

34. A nozzle as claimed in claim 32 or 33, wherein said valve means is movable by virtue of a plurality of annular bearings located within said elongate outer member.

35. A nozzle as claimed in any one of claims 32 or 33, wherein said valve means comprises a valve stem, which is widened at each end to form a valve head and a widened stem end.

36. A nozzle as claimed in any one of claims 32 to 35, wherein said biasing means comprises a compression spring.

37. A nozzle as claimed in claim 36, wherein said compression spring is located between said widened stem end and one of said plurality of annular bearings.

38. A nozzle as claimed in any one of claims 32 to 37, wherein the valve end of said elongate outer member is formed intoafrusto-conicalvalveseat and said valve head is formed to provide sealing engagement thereto.

39. Anozzleasclaimed in anyoneof claims32to 38, wherein the end of said elongate outer member remote from said dispensing end is contiguous with an axially extendible chamber.

40. A nozzle as claimed in claim 39, wherein said chamber comprises a bellows chamber.

41. Apparatus for dispensing sterile fluid substantially as hereinbefore described with reference to and as illustrated in the accompanying drawings.

42. A nozzle for dispensing fluid substantially as herein before described with reference to and as illustrated in the accompanying drawings.