Method and apparatus for generating a sterile infusion fluid

Description of equivalent WO 0232476 A2

METHOD AND APPARATUS FOR GENERATING A STERILE INFUSION

FLUID

0003Cross-Rcfcrcncc to Related Application

0004This application claims the benefit of U.S. patent application serial No. 60/241,662, filed October 19, 2000, and which is hereby incorporated by reference in its entirety.

0005Field of the Invention

0006The present application relates to the production and supply of sterile fluids in general and, more particularly, to a device for generating sterile infusion fluid "on

0007site" for blood-cleansing applications, such as hemodialysis, hemofiltration,

0008hemodialfiltration, or peritoneal dialysis, to name a few.

0009Background of the Invention

0010Sterile infusion fluid is used in various medical applications, particularly in

0011blood-cleansing applications such as hemodialysis, hemofiltration, hemodiafiltration,

0012or peritoneal dialysis treatments. In hemodialysis, for example, the infusion fluid is

0013generally used to prime an extracorporeal circuit of a blood-cleansing machine, prior to connecting a patient to the machine, and to rinse back the patient's blood at the end

0014of the treatment. Sterile fluid may also be administered to patients in the form of a

0015bolus, which may improve the patient's fluid status, blood pressure, etc. In the

0016practice of hemodiafiltration, plasma water is removed by filtration from the blood as

0017it traverses through the hemodialyzer cartridge and certain toxins or other material diffuses from the patient's blood. To compensate for this loss of plasma water, sterile fluid must be added either upstream^" or downstream of the hemodialyzer cartridge.

0018The sterile fluid used in these applications is generally a normal saline solution (e.g., a

0019solution having a sodium chloride concentration of 0.9 percent by weight) which is supplied pre-sterilized in one or two liter flexible bags. In some cases a Ringer's

0020Lactate Solution might be used. In peritoneal dialysis, sterile dialysate packaged in

0021flexible bags is typically infused into and subsequently emptied from the patient's

0022peritoneal cavity.

0023In dialysis clinics that have multiple dialysis stations, the clinic must purchase and store large volumes of sterile fluid. The costs involved in buying and storing the

0024pre-packaged sterile fluid may be significant. Further, peritoneal dialysis patients are

0025typically treated at home and thus, the cost and storage capacity for the required

0026amounts of sterile fluid, as much as 12 liters per day, become even more significant.

0027Summary of the Invention In one aspect, it is an object to generate a sterile fluid "on-site", thereby to

0028reduce or eliminate the costs associated with purchasing and storing large volumes of

0029sterile fluid.

0030There are a variety of machines that are designed to produce non-sterile fluids.

0031For example, one such machine is a dialysis machine that, in normal operation,

0032proportions dialysate concentrates and water to generate a dialysate fluid (a non-sterile

0033fluid). The dialysate fluid contains various electrolytes (e.g., sodium ions, chloride

0034ions, potassium ions, magnesium ions, etc.) at concentrations compatible with the patient's blood. Although in the practice of hemodialysis, the dialysate fluid must meet certain quality requirements, it is not necessary that the dialysate fluid be sterile.

0035The non-sterile fluid is acceptable because, during the dialysis process, the patient's

0036blood is protected by a dialyzer membrane which acts as a sterile barrier between the dialysate fluid and the blood.

0037The present application is directed to a method and a device for generating a

0038sterile infusion fluid. The method and device can be implemented in a number of ways, depending on particular needs. In accordance with one embodiment, the sterile

0039fluid generating device is an ancillary device designed to operate in conjunction with an existing dialysis machine, e.g., when the machine is not performing hemodialysis

0040treatments or used in other treatment or cleaning operations. In this embodiment, the

0041dialysis machine serves as a source of non-sterile dialysate fluid. This dialysate fluid

0042is supplied to the ancillary device which filters the dialysate fluid in accordance with a method recited herein, whereby dialysate fluid is filtered in a safe manner to render a

0043sterile and non-pyrogenic fluid which meets predetermined requirements to make it of

0044injectable quality. The sterile fluid produced by the present invention may be

0045designed to replace any type of sterile fluid used in medical processes, e.g. as a normal saline solution, peritoneal dialysate fluid. Ringer's lactate solution, etc., depending on the application.

0046It will be appreciated by persons skilled in the art that the present invention is

0047not limited to the particular sterile fluid applications described herein, namely,

0048hemodialysis, hemofiltration, hemodialfiltration, and peritoneal dialysis. The sterile

0049fluid generated by the methods and devices of the various embodiments disclosed herein can be suitable for use in any other application that may benefit from the

0050advantages described herein.

0051Brief Description of the Drawings

0052Fig. 1 is a schematic illustration of a fluid sterilization system in accordance

0053with a first embodiment, used in conjunction with a machine that produces a non- sterile fluid that is then filtered using the fluid sterilization system;

0054Fig. 2 is a schematic illustration of a fluid sterilization system in accordance

0055with a second embodiment, used in conjunction with a machine that produces a non- sterile fluid that is then filtered using the fluid sterilization system;

0056Fig. 3 is a schematic illustration of a fluid sterilization system in accordance

0057with a third embodiment in which the fluid sterilization system of Fig. 2 is modified

0058to include an overflow mechanism associated with a fluid reservoir;

0059Fig. 4 is a schematic illustration of a fluid sterilization system in accordance

0060with a fourth embodiment in which a control unit is added to the fluid sterilization system of Fig. 3;

0061Fig. 5 is a schematic illustration of a fluid sterilization system in accordance

0062with a fifth embodiment, wherein a hydrophobic sterile filter and a rinse fluid

0063collection container are used as aids to prime and rinse a sterilizing filter; and

0064Fig. 6 is a schematic illustration of a fluid sterilization system in accordance with a sixth embodiment similar to the embodiment of Fig. 3. Detailed Description of the Invention

0065Reference is made to Fig. 1 which illustrates a first embodiment. In this embodiment, a machine 40 is used as source of non-sterile fluid. The machine 40 can

0066be of any number of types of machines that produce non-sterile fluid. For example,

0067one such machine 40 is a dialysis machine that produces non-sterile dialysate fluid.

0068Suitable dialysis machines 40 may include but are not limited to the Fresεnius 2008E or 2008FI, available from Fresenius of Lexington, MA, the Althin System 1000,

0069available from Baxter/Althin of Miami Lakes. FL, the Cobe Centrysystem 3, available

0070from Gambro/Cobe of Lakewood, CO. Dialysis machine 40 includes a proportioning

0071system 11 that mixes water 44 and dialysate concentrates 42 at a suitable proportion to produce a dialysate solution 13 of a predetermined concentration. Dialysis machine 40 preferably includes a fail-safe mechanism which ensures that the final

0072concentration of the dialysate solution delivered to a dialyzer is within physiologic

0073limits (i.e. compatible with the ionic concentration of blood). This may be

0074accomplished by placing a conductivity sensing device 17 in the dialysate stream 31 followed by a series of valves 19, 21, and 23 and a bypass conduit 33. In the event

0075that the conductivity as measured by the conductivity sensing device 17 is outside

0076predetermined limits, valves 19 and 23 are closed while valve 21 is opened to redirect

0077the improperly proportioned dialysate fluid through the bypass conduit 33.

0078Additionally, dialysis machine 40 preferably includes a fluid balance system

007915 (flow balancing system), which controls the flow rates or volumes of the dialysate

0080fluid leaving the dialysis machine 40 though conduit 48 and the dialysate fluid

0081returning to the dialysis machine 40 via a dialysate return conduit 54. According to this first embodiment, a dialysate supply connector 50 and a dialysate return connector 52 of the dialysis machine 40 are connected to a dialysate inlet connector 62 and

0082dialysate outlet connector 72 associated with the sterilization system.

0083Between connectors 62 and 72 is a fluid conduit 60, that includes a first branch

0084or tee connector 64, a one way check valve 66 or similar type valve, and a second branch or tee connector 68. The first branch connector 64 is used to conduct a portion of the fresh non-sterile dialysate fluid to a filtration assembling including sterilizing

0085filters 93 and 95, while the second branch connector 68 is used to conduct a similar

0086amount of fluid into the fluid conduit 60 from an external source so as to satisfy the dialysis machine fluid balance system. According to this embodiment, the sterilizing

0087filters 93 and 95 preferably contain semi-permeable membranes 81 and 89, respectively. Each of the membranes 81, 89 preferably has a relatively high water

0088permeability property and a molecular weight cut-off small enough to retain bacteria,

0089endotoxin, and other potential particulate that may be present in the non-sterile dialysate fluid. A desirable range for molecular weight cut-off for the sterilizing

0090filters is about 5K - 35K. Daltons; however, this will depend upon the precise

0091application. The sterilizing filters 93, 95 may be medium or high flux dialyzers,

0092hemofilters, or other commercially available fluid sterilizing filters, such as used to sterilize pharmaceutical solutions and the like by conventional filtration methods.

0093Examples of dialyzers and hemofilters that can be used as sterilizating filters include

0094Fresenius dialyzers F40, F50, F60, F70, F80, F60M. F80M, available from Fresenius

0095of Lexington, MA, Baxter dialyzers CT HOG, CT190G, Syntra 160, available from

0096Baxter of Deerfield, IL, Althin Altraflux dialyzers 140, 170, 200, available from Baxter/Althin, Miami Lakes, FL, Ffospal dialyzers Filtral 12, 16, 20, available from

0097Hospal of Meyzieu, France, and Minntech hemofilters Memocor HPH 400, 1000,

00981400, available from Minntech Corporation, Minneapolis, MN. Other available filters

0099that may be used as sterilizing filters include Amicon hollow fiber membrane

0100cartridges H15P10-43, H15P30-43, available from Millipore, Bedford, MA.

0101A method of generating a sterile fluid in accordance with the embodiment of

0102Fig. 1 is described below. Fresh water 44, meeting the water quality requirements

0103described per the AAMI Standards for Hemodialysis Systems RD5-1992, is supplied

0104to the dialysis machine 40. Precautions concerning machine disinfection and rinsing should be done in accordance with dialysis machine operation instructions. Once the machine 40 has been adequately rinsed, dialysate concentrates 42 are supplied to the

0105dialysis machine 40 with the machine 40 set to produce a desired flow rate of

0106dialysate fluid. The machine 40 is then placed in a mode that begins to draw in the concentrates 42 and the fresh water 44 at predetermined proportions per the proportioning system 11, resulting in a dialysate fluid 13 that is compatible with

0107human blood but may not be sterile and may not be non-pyrogenic at this point. This

0108mode may be a set-up mode or a priming mode which generally precedes a machine treatment mode. The proportioned dialysate fluid 13 is delivered to the flow

0109balancing system 15 of the dialysis machine 40. The flow balancing system 15 can

0110include volumetric balance chambers or dual flow meters as are known in the art.

0111To ensure the dialysate fluid 13 is proportioned correctly by the proportioning system 1 1 , the conductivity of the dialysate fluid exiting flow balancing system 15 is

0112generally measured by a conductivity sensing device 17. This in combination with a series of valves 19, 21 , and 23, form a fail-safe mechanism that prevents improperly

0113proportioned dialysate fluid from exiting the dialysis machine 40 via the conduit 48

0114when the dialysate supply and return connectors 50 and 52 are not connected to their respective dialysis machine rinse ports (not shown). For example, when the dialysate

0115conductivity is outside predetermined limits, valves 19 and 23 are closed while 21 is

0116opened. This shunts the improperly proportioned dialysate fluid though the bypass

0117conduit 33 and back to the flow balancing system 15. The improperly proportioned dialysate fluid then flows through a conduit 46 leading out to a drain.

0118When the conductivity is within the predetermined limits, the bypass valve 21

0119is closed and valves 19 and 23 are opened. This allows properly proportioned

0120dialysate fluid to flow through the dialysate supply conduit 48, through conduit 60,

0121and into the dialysate return conduit 54 which leads back to the flow balancing system 15 and then to a drain or the like. In order to get a portion of the dialysate fluid to

0122pass through the sterilizing filters 93, 95 via conduit 74, fluid under pressure is injected into conduit 60 at the branched tee connector 68. This can be accomplished

0123by opening a clamp 362 of a conduit 154 that is in fluid communication with a fresh

0124water source 44 that typically operates above 15 to 20 psi. A pressure regulator 152 is used to regulate the downstream fluid pressure inside the conduit 154 to a desired

0125level. This setting, which is set to between 2 to 10 psi, preferably between 3 to 6 psi, provides a means to control how fast this fluid is injected into the dialysate path. The

0126precise setting will depend upon a number of factors, including factors that are

0127application specific, such as the type of sterilizing filters 93, 95, etc. For example, the

0128fluid pressure can be increased to an elevated pressure beyond 10 psi (e.g., 15 psi) so long as the diaslysis machine 40 is capable of operating at this elevated pressure and

0129so long as the sterilization filters 93, 95 can withstand such an elevated pressure. It

0130will therefore be appreciated that the user will set and adjust the setting so that the

0131proper and desired amount of non-sterile dialysate fluid is flowing into the filtration

0132assembly (sterilizing filters 93, 95), while at the same time this elevated pressure is

0133within operating conditions for the machine 40 and the sterilizing filters 93, 95.

0134The flow balancing system 15 serves to regulate both the dialysate supply flow

0135rate passing through conduit 48 and the dialysate return flow rate passing through conduit 54. Generally, the flow balance system 15 regulates the flow rates so that they

0136are substantially equal or within a predetermined acceptable range. As a result of this,

0137the injection of fresh water into the conduit 60 at the branched tee connector 68 serves

0138to increase the fluid pressure residing in the fluid path defined by conduits 31, 48, 60, 54, and 35. This is due to the fluid conduits being relatively noncompliant. The

0139increase in fluid pressure in conduit 60 causes a portion of the dialysate fluid to be

0140diverted into conduit 74 that connects to the inlet port 81 of a first sterilizing filter 93.

0141Preferably, a second sterilizing filter 95 is used as a redundant filtration stage to assure sterility of the filtered fluid in the event one of the filter fails during the filtration process. The sterilizing filters 93, 95 can consist of two single filter

0142cartridges, or it can consist of a single cartridge unit having multiple filtration

0143sections. Although it is possible to use a single filtration stage (i.e. without redundant

0144filtration) as the final filtration unit, it is generally undesirable due to patient safety issues that may arise should the filter fail during operation. Redundant filtration is generally required by industry standards. In the embodiment of Fig.1 , two separate sterilizing filters 93, 95 are used. The first sterilizing filter 93 contains two

0145compartments 80 and 82 that are separated by a semi-permeable membrane 81. Fluid to be filtered enters the inlet port 78 leading to a first upstream compartment 80. Fluid

0146is then filtered across the semi-permeable membrane 81 and into a first downstream

0147compartment 82. As previously mentioned, the semi-permeable membrane 81 serves

0148to filter the non-sterile dialystate fluid and remove any impurities that may exist. The

0149degree of filtration depends upon a number of factors, including the specific type of filter being used.

0150The once filtered dialysate fluid then exits the first downstream compartment

015182 through outlet ports and passes through conduits 84 and 86 that leads to a second

0152upstream compartment 88 of the second sterilizing filter 95. The once filtered dialysate fluid is then filtered across the second semi-permeable membrane 89 and flows into the second downstream compartment 90 of the second sterilizing filter 95, thereby being filtered twice. The twice filtered dialysate fluid exits the second

0153sterilizing filter through an outlet port 92 that is in fluid communication with a sterile

0154collection bag 98 or any other type of collection device or container that is suitable for storing a sterilized fluid. Starting and stopping the flow of dialysate fluid through the sterilizing filters 93, 95 and into the collection bag 98 may be accomplished by

0155opening a valve, such as a tubing clamp 120 or 122. This allows a new collection bag

015698 or new sterilization filters 93, 95 to be used in the process. In addition, it should be understood that number of collection bags 98 can be filled at the same time by assembling multiple bags 98 to a common manifold 100. It should be understood that the flow rate at which the collection bag 98 is being filled should not exceed the rate at which the dialysis machine 40 is producing

0157dialysate fluid. Preferably, the rate at which the collection bag 98 is being filled

0158should be less than that of the dialysate flow rate such that there is a positive flow of

0159fresh dialysate fluid though the check valve 66. This assures that the water being

0160injected into the conduit 60 at the branched tee connector 68 will not flow in a

0161retrograde fashion through the check valve 66. This can be further explained as follows. Provided there is a positive flow of dialysate through the check valve 66, the

0162pressure upstream of the check valve 66, such as at the branched tee connector 74 will

0163be higher than the pressure downstream of the check valve 66, such as at the branched

0164tee connector 68. In this case, water that is being injected into conduit 60 at the branched connector 68 will flow toward conduit 54 leading back to the dialysis

0165machine 40 since it cannot flow toward an area of higher pressure (i.e., towards the

0166check valve 66 and connector 74). The rate at which sterile fluid is generated can be controlled by adjusting the pressure regulator setting 152. Increasing the output

0167pressure, increases the filling rate while decreasing the pressure, decreases the rate. Additional factors that may affect the filling rate is the hydraulic permeability of the

0168sterilizing filters 93, 95 and the associated hydrostatic head of the sterile collection

0169bag 98 relative to the inlet pressure to the sterilizing filters 93, 95. At a point when the collection bag 98 is full or when either of the clamps 120

0170or 122 are closed to prevent flow through the sterilizing filters 93, 95, the dialysate pressure will increase to a maximum pressure as defined by the setting of the pressure

0171regulator 152. As known in the art, this pressure would be considered the operating pressure at the zero or no flow condition for the given pressure regulator setting. At this pressure, the spring loaded diaphragm within the pressure regulator 152 closes to

0172prevent fluid from passing through the regulator 152 (i.e. from the water source 44

0173into the conduit 154).

0174In the event that the dialysis machine 40 does not produce a properly

0175proportioned solution, such as can occur if the concentrate solution were to run out during the process, a dialysis machine alarm condition will be generated that places

0176the dialysis machine 40 in a safe state. In particular, the improperly proportioned

0177dialysate will be detected by the conductivity sensing device 17 which will create an

0178out-of-conductivity alarm condition that immediately puts the dialysate flow path into a bypass mode, i.e. valves 19 and 23 are closed and valve 21 is opened. When this

0179occurs, flow through conduits 48 and 54 stops. Flow of water into conduit 60 at the branched tee connector 68 will then cease since flow is dead-ended in both directions.

0180For example, closed valve 23 prevents flow toward connector 72 while check valve 66 prevents flow toward the branched tee connector 64. It will be understood by those

0181skilled in the art, that the present apparatus and method allows only properly

0182proportioned fluid which has been generated by the dialysis machine 40 to be filtered

0183across the sterilizing filters 93, 95 while preventing water used to pressurize the dialysate fluid path from being filtered across the sterilizing filters 93, 95. In this

0184respect, the invention assures that the filtered fluid collected in the sterile collection

0185bag 98 has been properly proportioned by the dialysis machine 40 and has not been compromised or contaminated by fluid being injected into the conduit downstream of the check valve 66. Fig. 2 schematically illustrates an alternative configuration of the embodiment of Fig. 1. In the configuration of Fig. 2, a fluid reservoir 10 containing a fluid 12 is

0186used instead of water from a pressurized water source 44 as in Fig. 1. The fluid 12

0187contained in the reservoir 10 can be water or some other aqueous solution provided it

0188is both miscible with the fluid being generated by the dialysis machine 40 and compatible with the materials in the dialysis machine fluid path. In order to use the

0189fluid 12 contained in the fluid reservoir 10 in the process of making sterile fluid, it

0190must be pressurized. This may be accomplished in several ways. In the configuration

0191of Fig. 2, this is accomplished by using the dialysis machine blood pump 16, a back pressure regulating valve 36, and associated arterial and venous bloodline tubing segments 14 and 24 respectively. In this configuration, the blood pump 16 is used to

0192draw fluid 12 from the fluid reservoir 10 and pump it through the arterial drip

0193chamber 20 and into the dialysate path conduit 60 at the branched tee connector 68.

0194This fluid mixes with the dialysate fluid generated by the dialysis machine 40 flowing though conduit 60 and continues toward a second branched tee connector 70 that is in

0195fluid communication with a conduit leading back to the fluid reservoir 10. This

0196conduit may include a venous drip chamber 28 and may pass though an air detector 32

0197device on the dialysis machine as is known in the art. A back pressure regulator 36 is preferably used as a means to generate a back pressure in the fluid path between the blood pump 16 and pressure regulator 36. Since a portion of this fluid path is in fluid

0198communication with the dialysate fluid flowing through conduit 60, one is able to

0199achieve the same effect as the pressurized water source as described in the first

0200embodiment of Fig. 1. According to this embodiment, the blood pump 1 is turned on to a desired rate and air is purged from arterial and venous bloodline tubing segments.

0201The pressure monitoring lines on the bloodline drip chambers are not connected to

0202their respective pressure monitoring ports on the dialysis machine 40. This is to avoid

0203creating nuisance related pressure alarms during the process of making sterile fluid.

0204The inventors have found, however, that it may be necessary on some dialysis machines to apply a fixed pressure to the venous pressure monitoring port on the

0205dialysis machine to avoid low TMP alarms that prevent the blood pump from

0206operating. This may be accomplished by attaching a tubing segment to the venous

0207pressure port, using a syringe to generate a desired venous pressure in the range of 100

0208to 500 mmHg, preferably 200 to 400 mmHg, followed by clamping the tubing to hold the pressure at a constant level. Since the venous pressure port on the dialysis

0209machine is a protective mechanism to guard against a blood loss hazard when

0210dialyzing a patient, there is no concern here since a patient is not being treated at the

0211same time the machine is being used to make a sterile fluid. The rate at which sterile fluid is generated is primarily dependant upon the blood pump rate, the back-pressure

0212regulator setting, the hydraulic permeability of the sterilizing filters 93, 95, and the

0213associated hydrostatic head of the sterile collection bag 98.

0214One advantage of this embodiment is that it provides a means to use a separate source of fluid for those situations where the water supplied to the dialysis machine or machines may be capacity limited. Another advantage is that when the reservoir runs

0215out of fluid, air enters the bloodline circuit and is subsequently detected by the dialysis

0216machine air detector 32 which immediately disables the blood pump. In this manner. one can only make as much sterile fluid as initially contained in the reservoir and

0217therefore makes it impossible to overfill the collection bag.

0218As mentioned previously, there are many ways to pressurize fluid. The

0219embodiment of Fig. 2 showed a method using the dialysis machine blood pump and a

0220back pressure regulating valve. It will be appreciated that a closed, pressurized fluid

0221reservoir in fluid communication with the dialysate path can also be used, whereby

0222pressure inside the reservoir is driven using a compressed gas source, such as air,

0223nitrogen, etc.

0224An alternative to the embodiment of Fig. 2 is shown schematically in Fig. 3.

0225Here the fluid contained in the reservoir 162 is made up of the dialysate fluid exiting

0226the machine through conduit 46. The fluid reservoir 160 includes a weir 163 such that

0227excess dialysate fluid overflows into a separate compartment that leads out to the

0228drain. This has the advantage of always having a full reservoir of fluid used in the process of making sterile fluid. A second advantage is that this configuration provides

0229an efficient use of fluid being used in the process. Other than the differences in fluid

0230flow path resulting from the above structural differences, the method of generating a

0231sterile fluid in accordance with the configuration of Fig. 3 is carried out substantially

0232as described above with reference to the embodiment of Fig. 2.

0233Another embodiment of the invention is illustrated schematically in Fig. 4.

0234The configuration of this embodiment may be identical (both structurally and

0235functionally) to that of the above embodiments except that a control unit 200 may be

0236used to automate part of the process. For example, a load cell 230, may be used as input device to the control unit as a means to regulate how much sterile fluid is placed into one or several of the collection bags 98 or 1 10, respectively. Operation may be

0237such that when the load cell 230 senses the collection bag is full or at a desired set

0238point, the control unit may close a pinch valve 240 that is positioned on the bag inlet

0239tubing conduit 96. When the pinch valve is closed, the user can load empty bags and restart the filling process.

0240Another feature of the embodiment of Fig. 4 is an added safety mechanism

0241that would aid in preventing fluid circulating back and forth from the reservoir 160

0242from entering the conduit 74 leading to the sterilizing filters 93, 95. This may be accomplished by using a flow sensor device 210 in the dialysate conduit 60. The flow

0243sensor device 210 may be any one of those known in the art, such as flow switch, a

0244turbine style flow meter, an ultrasonic flow meter, or a flow meter based on a heated

0245thermistor or thermal dilution methods. Operation is such that when dialysate flow is

0246stopped, such as when the machine goes into a bypass state, the flow sensor 210 detects the change. This signal is then used as an input to the control unit 200, which closes a solenoid actuated valve 220 to stop the flow of fluid toward the sterilizing

0247filters. In this manner, even if the check valve 66 were to fail, fluid downstream of the

0248check valve would not be able to back up into the sterilizing filters. After dialysate flow from the machine has been re-initiated, the flow sensor 210 can send a signal to

0249the control unit 200 to re-open valve 220 and thus resume making sterile fluid.

0250Fig. 5 schematically illustrates an alternative configuration of the embodiment

0251of Fig. 3. In the configuration of Fig. 5, connection of the dialysate supply connector

025250 is made directly to an inlet port 83 of the upstream compartment 80 of the first sterilizing filter 93. Connector 63, which is at the inlet end of conduit 60, is connected to an outlet port 78 of the upstream compartment 80 of the first sterilizing filter 93. Dialysate fluid (not sterile) that is not filtered across the first semi-permeable

0253membrane 81 , flows within the upstream compartment 80 to outlet port 78. The

0254dialysate fluid then flows within conduit 60 and conduit 54 as it returns to the

0255machine 40. This embodiment operates in substantially the same manner as the

0256embodiment shown in Fig. 4 in that as the fluid pressure increases in the fluid path, more and more non-sterile dialysate fluid is conducted across the semi-permeable

0257membrane 81 as a result of the increase in system pressure.

0258In addition, a sterile hydrophobic filter can be placed at an upper end of the

0259sterilizing filters that is in fluid communication with the downstream compartment 82 of the first sterilizing filter 93 and the upstream compartment 88 of the second sterilizing filter 95. In the outlet conduit 300 of the second sterilizing filter 95, a tee

0260junction is used to divert the flow to either an initial rinse collection bag 330 or the

0261sterile collection bag 98. The advantages of this configuration is to aid in priming the sterilizing filters and performing an initial rinse of the sterilizing filters that may be

0262necessary to flush out residual chemicals as a result of the filtering manufacturing

0263process. This will become more evident as the priming method is described.

0264Generally, filters are shipped in a dry or empty state and thus must be primed and

0265rinsed prior to use. Upon connecting up dry sterilizing filters as shown in Fig. 5, the upstream compartment 80 of the first sterilizing filter 93 is purged of air when

0266dialysate flow through conduit 48 is initiated in a similar manner as priming a new

0267dialyzer before treatment. Once the air has been purged out of compartment 80, fluid

0268will filter across the first semi-permeable membrane 81 and flow into the downstream compartment 82. Because the downstream compartment 82 and the upstream

0269compartment 88 are in fluid communication, both compartments will fill from the

0270bottom end and thus purging air out of a hydrophobic filter 250. After most of the air has been purged out through the hydrophobic filter 250, the fluid will come into

0271contact with the hydrophobic filter 250.

0272Because the filter 250 is of a hydrophobic type, the fluid will not be able to

0273pass though the hydrophobic membrane of the filter 250 as is known in the art. The

0274fluid in the upstream compartment 88 of the second sterilizing filter 95 will then filter across the semi-permeable membrane 89 and flow into the downstream compartment

027590. Here the twice filter fluid flows through conduit 300 that leads to a tee. Initially,

0276clamp 312 is kept in a closed position and clamp 310 is open to direct the outlet air and fluid to the initial rinse collection bag 330. Given the rinse collection bag 330 is a fixed volume, this permits a predetermined amount of fluid to be rinse through the

0277sterilizing filters prior to collecting fluid in the sterile collection bags 98, 110. This

0278volume can be specific to ensure any residual components in the sterilizing filter are

0279substantially removed. A check valve 320 or the like may be placed in the conduit

0280302 leading to the rinse collection bag to prevent flow of fluid from this bag to the sterile collection bags 98, 110. It is preferred to keep the rinse collection bag

0281suspended below the sterile collection bags such that it remains at a lower hydrostatic

0282pressure than the other bags. After the rinse bag is full, clamp 310 can be closed and

0283clamp 312 can be opened to begin collecting the sterile fluid in the same manner as described in the previous embodiments. Now referring to Fig. 6 which illustrates yet another embodiment. The

0284embodiment of Fig. 6 is similar to the embodiment of Fig. 3 and therefore, like

0285elements have been numbered alike. The conduit 14 includes a portion 402 that acts

0286as a pump inlet line for drawing the fluid contained in the fluid reservoir 160 and a

0287pump outlet line 404 that delivers the pumped fluid under pressure to the connector 68

0288(which is at a location downstream of the check valve 66). In this embodiment, a pump recirculating line 400 is provided and includes a first end and a second end with

0289the first end being fluidly connected to the pump inlet line 402 and the second end is

0290fluidly connected to the pump outlet line 404. The pump recirculating line 400

0291contains the back pressure regulating valve 36 which operates in the same manner as in the embodiment of Fig. 3.

0292The back pressure regulating valve 36 functions so that the fluid being

0293returned through the pump recirculating line 400 constitutes higher pressure fluid that

0294is being pumped by pump 16 as opposed to fluid contained in the conduit 60 (as in Fig. 3). In addition, another advantage of this embodiment is that the fluid being

0295returned does not have to be returned back the fluid reservoir 160 but rather only has

0296to be returned to the fluid inlet side of the pump 16, e.g., to the pump inlet line 402.

0297Conventional connectors, such as T-connectors, can be used to provide fluid

0298connections between the conduits. The other components of this embodiment function in the same manner and thus the observed pressure increase in the fluid path

0299results in non-sterile dialysate fluid flowing to the sterilizing filters 93, 95 for sterilization thereof. The present application provides several apparatuses and methods for

0300conveniently and effectively producing a sterilization fluid in an "on-site" manner

0301using a machine, such as a dialysis machine. Advantageously, the present sterilization

0302system is designed to be fitted with conventional equipment that produces non-sterile

0303fluid. Particular utility is found when the sterilization system is used with a dialysis

0304machine as a means for producing sterile infusion fluid.

0305It will be appreciated by persons skilled in the art to which this invention pertains that the invention is not limited to the preferred embodiments and

0306configurations described above and with reference to the accompanying drawings. Rather, the scope of the invention is limited only by the following claims.