Process and apparatus for removal of unwanted fluids from processed blood products

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1995

KINGDOM OF BELGIUM

PATENT

NUMBER OF

PUBLICATION

NUMBER OF

DEPOSIT

09300901

MINISTRY OF ECONOMIC AFFAIRS

Classif

Boarding school.

Date of issue on

A61M B01D

May

The Minister of Economic Affairs

Having regard to the Paris Convention of March 20, 1883 for the Protection of Industrial Property;

Considering the law of March 28, 1984 on patents for invention, in particular article 22;

Considering the royal decree of December 2, 1986 relating to the request, the issue and the maintenance in force of invention patents, in particular 1 article 28;

Having regard to the minutes drawn up on 02 September 1993 at 2:50 p.m. at the Industrial Property Office

STOPPED

ARTICLE 1.- It is issued to: PALL CORPORATION

Northern Boulevard 2200, East Hills, NEW YORK 11548 (ETATS-ÜNIS D'AMERIQUE) represented by: CLAEYS Pierre, GEVERS Patents SA, Brussels Airport Bus. Park-Holidaystr. 5-1831 DIEGEM.

a patent for an invention of 20 years duration, subject to the payment of annual fees, for: PROCESS AND APPARATUS FOR THE SEPARATION OF UNDESIRABLE FLUIDS FROM TREATED BLOOD PRODUCTS.

INVENTOR (S): Page Roger Edward, Seafront 392, Hayling Island, Hampshire POU OBB (GB); Lowe Graham Desmond, Burgess Close 6, Hayling Island, Hampshire POU 9QT (GB); Morris Keith Stuart, Brookside Cottage, Soutnfourne Avenue 21 , Emsworth, Hampshire P018 8BB (GB); Markovich Vlado Ivan, Old Estate Road 11, Glen Cove, New York

PRIORITY (S) 02.09.92 GB GBA 9218581

ARTICLE 2.- This patent is granted without prior examination of the patentability of the invention, without guarantee of the merit of the invention or of the accuracy of the description thereof and at the risk and peril of the applicant (s) .

Brussels, May 30, May 30, 1995

BY SPECIAL DELEGATION:

WUYTS L Director.

- 1,093 WHERE in UifW

Method and apparatus for the separation of unwanted fluids from treated blood products

The present invention relates to the separation of undesirable fluids from treated blood products.

As used herein, the `` blood product '' refers to any treated or untreated fluid associated with living organisms, in particular blood, including whole blood, hot or cold blood and stored or fresh blood, blood treated, such as blood diluted with a physiological solution, in particular saline, nutritive and / or anticoagulant solutions but not being limited to such solutions, one or more components of the blood, such as platelet concentrate (PC), platelet rich plasma (PRP), platelet free plasma, platelet poor plasma, plasma, concentrated red blood cells (PRC) or inflammatory rind, similar blood products from blood or a blood component or from bone marrow. The blood product may include leukocytes or may be treated to separate the leukocytes. As used herein, the blood product refers to the components described above and similar blood products obtained by other means and with similar properties.

When a blood product is treated with a functional biological device, there is a clinical risk that gases, including air, remain in the treated blood product.

The residual gas sources are the functional biological device carrying out the process and the tubes used to pass the product

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- 2 blood to and from the device. There may also be gases present in the container into which the treated blood product is transferred.

The term functional biomedical device as used herein can be any of a number of devices or assemblies in which air or gases are present and / or can collect or form, or must be moved before using the assembly. Examples of functional biomedical devices are a filter, such as a leukocyte depression filter, a separator device, such as a platelet concentrator, preferably a non-centrifugal platelet concentrator, a demister or a pump. The functional biomedical device may also include a device for destroying biological impurities, such as a high intensity light wave chamber or a device for sampling a biological liquid. Examples of devices usable with red blood cells are described in US Patents 4,925,572 and 4,923,620; an example of a device which can be used with wafers is described in US Pat. No. 4,880,548. It is understood that the invention is not limited by the type of functional biomedical device used in a specific assembly.

The presence of these residual gases can reduce the quality of the stored biological fluid and can thus reduce the period of time during which the biological fluid can be stored. In addition, these gases reduce the storage capacity of the containers in which the blood product is kept. In addition, these residual gases, during a transfusion, can enter the transfusion container and cause

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- 3 an embolism. The clinical consequences of this are well described in the literature.

It is therefore important to leave as little gas as possible, ideally not to leave gas, in the blood product being treated. Paragraph IV 2.2.2.1 of the European Pharmacopoeia specifies that less than 5 ml of gas must remain in the container for the blood product treated.

It is also important that any treatment is completely free of any bacterial contamination from the environment.

It has previously been proposed to provide in the functional biomedical device, an outlet for purging the air collected in the device. The release may include a hydrophobic filter medium; see, for example, GB-A-1,585,989 which separates air from a filtered blood product. One problem with such an arrangement is that it only treats the air that is in the location of or reaching the functional biomedical device. It does not remove air from the functional biomedical device - with the treated blood product.

In another arrangement, a bypass conduit is provided between a first container for the untreated blood product (often called the donor bag) and a second container for receiving the treated blood product (often called the transfer bag). The bypass conduit bypasses the functional biomedical device and includes a clamp or relief valve or both, to isolate the bypass conduit.

After the blood product has been processed from the donor bag, the gases in the transfer bag are sent to the donor bag, now emptied by the bypass loop, after opening the clamp / shut-off valve. The transfer bag is

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- 4 either compressed with the hand or placed in a device to express the plasma so as to expel the gases through the bypass loop. During this derivation, the functional biomedical device is isolated.

A problem with this arrangement is a significant risk of destruction of the blood product beyond the prince / release valve in the bypass if it is broken / defective before use or it is left open accidentally. The consequence of this is that the treated blood product can be heavily contaminated with a volume of untreated blood product. For example, if the treatment involves reducing leukocytes in a blood product, then the treated blood product will have a higher level of leukocytes than desired.

According to another arrangement, a device is provided in the passage located between the functional biomedical device and the transfer bag, which comprises an outlet or a filter for the release of protection against bacteria. This is how the gases in front of the blood product are moved through the opening or filter to the atmosphere during the processing of the blood product. These gases can be stored and returned to the system to facilitate recovery of the blood product.

However, this does not eliminate the gases already in the transfer bag, which can constitute 50% of the total volume of gas which can accumulate in the transfer bag.

A third possibility, used when the functional biological device is a leukocyte filter, is to compress the transfer bag to re-pass the gases accumulated from the transfer bag through the leukocyte filter into the donor bag. However, this arrangement lacks reliability because a minimum pressure must be applied oajüüüui

- 5 to the transfer bag to overcome the bubble point of the filtering medium in the leukocyte filter to bring the gases out of the transfer bag. This depends on the user and cannot be done satisfactorily all the time. In addition, if the crushing or compression is stopped and re-initiated, there is a certain risk of displacement of the retained stains from the leukocyte filter in the treated blood product.

Similar problems can arise when separating supernatant liquids from red blood cell detergents and when centrifuging blood products. This supernatant is an undesirable fluid which must be discarded before use.

According to a first aspect of the invention, there is provided a method for separating the undesirable fluid from a treated blood product, comprising passing the blood product from a first closed container through a functional biomedical device for treating blood products, flow of the treated blood product and the undesirable fluid from the functional biomedical device, separating the undesirable fluid from the treated blood product and passing the undesirable fluid through the opening comprising a barrier medium which allows the passage of the undesirable fluid but which prevents the passage of the treated blood product.

According to a second aspect of the invention, there is provided an apparatus for the separation of an undesirable fluid from a treated blood product, comprising a first container for containing the product to be treated, a first passage connecting the first container to a biomedical device. functional and a second passage starting from the above-mentioned functional biomedical device, characterized in that an outlet passage leads to the first passage or first container and includes a barrier medium to prevent passage of the

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- 6 blood products treated to allow the passage of undesirable fluid to the first container.

The following is a more detailed description of certain embodiments of the invention, given by way of example, reference being made to the appended drawings, in which:

Figure 1 is a schematic diagram of an apparatus for depleting the leukocyte content of a blood product and comprising a filter usable for separating the air from the treated blood product.

Figure 2 is a schematic view of an apparatus for treating a blood product and comprising a filter usable for the separation of air from the treated blood product.

FIG. 3 is a schematic cross-sectional view of an embodiment of medium forming a barrier to liquids usable in the apparatus of FIG. 2.

Figure 4 is a schematic view of another apparatus for treating a blood product and comprising a filter usable in the separation of air from the treated blood product.

The apparatus of Figure 1 includes a first closed container in the form of a donor bag to hold a blood product, such as red blood cells or whole blood or platelets. A tube leads from the donor bag 10 to a functional biological device in the form of a blood filter for the depletion of leukocytes 12, which can be of the type described in patent GB-A-2,211,755.

The outlet leading to the filter 12 is connected by a tube 13 to a second container in the form of a closed transfer bag 14. A clamp 15 which can be used manually is provided on this tube 13 to allow the opening and closing of the tube 13 As an alternative, a check valve could be provided.

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- Ί An outlet tube 16 leads from the transfer bag 14 to the donor bag 10 and comprises a filter 17. The filter 17 is a hydrophobic filter having a porous degree sufficient to separate gas, such as oxygen, from air or the like, which may be present in a blood, fluid, i.e., blood or blood components that are processed in the system. Such a porous degree can be less than 5 μτα and, advantageously, 0.2 μτα. or 0.1 gm. A clamp 18 which can be actuated manually is provided in the duct 15 between the filter 17 and the tube 11 to open and close the duct 15.

In use, initially the clamp 15 is open and the clamp 18 is closed. The donor bag 10 containing, for example, whole blood is connected to the tube 11. The leukocyte filter 12 is primed by compressing the donor bag 10 and the blood passes through the filter 12 to the transfer bag 14. At the end of the transfer, the clamp 15 is closed and the residual leukocyte-depleted blood product in the tube 13 between the clamp 15 and the transfer bag 14 is taken into the transfer bag 14.

At this time, the transfer bag 14 is filled with leukocyte-depleted blood and air. The source of this air comprises the filter 12 and the residual air in the transfer bag 14.

The transfer bag 14 is then compressed manually or placed in a device for expressing plasma (not shown) and the clamp 18 is open. The air in the transfer bag is then brought into the tube 16 towards the filter 17. The filter 17 has a pore size which allows the passage through the air filter, but which prevents the passage of the treated blood. As mentioned above, the pore size thereof is generally less than 5 μπι and can be 0.2 mm or 0.1 gm.

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The air passes from the filter 17 to the donor bag 10 and, when all of the air has been expelled from the transfer bag 14, the clamp 18 is closed and the clamp 15 is open. The air in the donor bag 10 will then pass through the tube it and move the blood in the tube 11 and the leukocyte filter 12 to the transfer bag 14, without air entering the transfer bag 14.

The transfer bag 14 is then separated from the tube 13 and the tube 16.

The device has the advantage that during use it is completely closed, which allows the treatment and separation of air without any bacterial contamination from the environment. If, during the processing of the blood product, blood product should pass beyond the clamp 18, the filter 17 will prevent the passage of the blood product towards the transfer bag 14.

In addition, since the air is moved from the transfer bag 14 after treatment, all of the air can be separated. The operation is simple and can be carried out quickly. The only additional equipment required, a tubular extractor and a device for expressing plasma, is readily available under the circumstances of use of the device.

Air is not drawn through the leukocyte filter 12 during its separation and therefore does not present the problems associated with the movement of air through a used leukocyte filter.

A similar apparatus and method can be used to separate other unwanted fluids from treated blood products. For example, supernatants can be separated from the wash and centrifuge of the red blood cells. In this case and, when the liquid is a liquid oaaooatn

- 9 visible, the filter 17 will be a hydrophilic filter which may have a pore size of less than 5 μιη, advantageously 0.1 gm or 0.2 μιη.

The apparatus and method described above for the frame of Figure 1 should not be used in conjunction with a functional biological device (such as the leukocyte filter 12 described above). The tube 16 can be used only in conjunction with a transfer bag 14, or its equivalent, containing a treated blood product.

A second embodiment of the invention will now be described with reference to Figure 2. Figure 2 shows a blood processing assembly, which includes a first container or donor bag 111 and a second container or transfer bag 112 , as well as a conduit 113, 114 connecting the first container 111 to the second container 112, and comprising interposed between the first container 111 and the second container 112, at least one functional biomedical device 115. The functional biomedical device 115 can be associated with a release filter 140. The release filter 140 comprises an inlet 141 for ambient air, a filter medium 142 for separating the bacterial material from the air and an outlet 143 connected to a inlet of the functional biomedical device 115 for supplying sterile air to the inlet for moving the blood product through the assembly.

A gas collection and displacement loop 120 is in communication for a fluid with the first conduit 113 and the second conduit 114.

The loop 120 is a flow path for separating the gas from the biological fluid flow path and, optionally, for using the collected gas so as to recover additional biological fluid. The loop 120 includes a conduit 122 in communication for a fluid with the second container

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- 10 112 and a conduit 12 3 in communication for a fluid with the first container 111. A communication for a fluid for each conduit 122, 123 can be established respectively by any type of junction 126 and 125. As illustrated, the junction 126 is a Y-type junction and junction 125 is a flexible T-type junction.

The gas collection and displacement loop 120 comprises a third container 121 interposed between the conduit 122 and the conduit 123. The third container 121 is used to collect and store the displaced gas. The third container 121 is a flexible bag which can be compressed or crushed in order to transfer the gas from the third container 121 into the first container 111 and / or the conduit 113. Other arrangements are possible; for example, the conduits 122 and 123 may be attached to a syringe or the like, which could draw the gas from the treatment assembly into the conduit 122 and which could transfer the gas collected in the syringe into the first container 111 and / or the conduit 113. It is understood that the gas collection and displacement loop functions so that the fluid charged with leukocytes is prevented from contact with the fluid depleted in or devoid of leukocytes.

The gas collection and displacement loop 120 also comprises a medium forming a barrier to liquids 124 arranged in the conduit 123 between the third container 121 and the junction 125.

The liquid barrier medium 124 may be any of a variety of systems and devices which are capable of separating gas, such as air, oxygen or the like, which may be present in a system liquid blood processing, i.e. blood and / or blood components that are processed in the system. Media forming

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- The barrier to suitable liquids are those described in international patent application No. WO 91/17809 but are not limited thereto.

The liquid barrier medium is particularly suitable for use in closed and / or sterile systems. Suitable liquid barrier media are a porous liquophobic medium. In some embodiments, the liquid barrier media have a pore size small enough to exclude the passage of bacteria through the liquid barrier medium. Since such a porous liquophobic medium is not wettable by the biological fluid treated in the system, the gas in the system which is in contact with the liquophobic medium will pass through it and the blood product will not be absorbed by the porous liquophobic medium. In some embodiments, the pore size of the porous liquophobic medium will be 0.2 µm or less to form a satisfactory bacterial barrier.

The term liquophobic as used is actually the opposite of the term liquophilic; thus a porous liquophobic material has a critical wetting surface tension lower than the surface tension of the applied liquid and is not wetted quickly or spontaneously for the applied liquid. Liquophobic materials can also be characterized by a high contact angle between a drop of liquid placed on the surface and the surface. This high contact angle reveals poor wetting.

The liquid barrier medium may comprise a liquophobic membrane as described above, or may comprise other structures which allow the passage of gases, but which do not allow impurities to enter. In an embodiment shown in Figure 3, the barrier medium

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- 12 for liquids 124 comprises a multilayer microporous membrane in an envelope. The first layer 150 of the microporous membrane can be wettable with liquids, that is to say liquophilic. The liquophilic membrane allows the passage of gas as long as it remains unsaturated with the liquid during treatment. The second layer of microporous membrane 151 is not wettable by the liquid being treated by the distribution system, that is to say that the second layer is liq uophobic. Examples of liquophilic and / or liquophobic media are those described in international patent application No. WO 91/17809.

The liquophilic layer 150 of the multilayer microporous membrane is advantageously positioned in the envelope on the inside of the medium forming a barrier to liquids. In this way, the liquophilic layer 150 is the first layer to be contacted either by the gas which is to be brought from the liquid transfer or distribution system or by the liquid transferred or distributed by the system.

The liquophobic layer 151 is also capable of admitting the passage of gases. The liquophobic layer 151 can be superimposed on the liquophilic layer 150, advantageously positioned on the outside of the medium forming a barrier to liquids. Due to the liquid-wettable nature of the liquophilic layer 150 and the non-wettable nature of the liquophobic layer 151, the gas which comes into contact with the liquid barrier medium passes through the liquid barrier medium insofar as the liquophilic layer 150 remains not wetted by the liquid. Once the liquophilic layer 150 is wetted with liquid, the gas can no longer pass through the liquophilic layer 150 so that the liquid barrier medium becomes obstructed or inactivated. The combined liquophobic and liquophilic membrane 150, 151 is

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- 13 particularly advantageous when the medium forming a barrier to liquids is used in a closed sterile system.

It will be noted that the liquophilic and liquophobic layers 151, 151 can be two separate layers or they can be linked together. In addition, a plurality of separate membrane elements could be combined together to form the liquophilic microporous membrane 150 and a plurality of separate membrane elements could be combined together to form the liquophobic microporous membrane 151. By the term plurality is meant two or more of two elements. The plurality of separate membrane layers can be prepared individually and bonded together by various means known to those skilled in the art. For example, the separate membrane layers can be bonded together by drying two or more layers maintained in intimate contact. Or, by way of example and without any limitation, the separate membrane layers can be prepared by passing the material used to form the membrane over a hot drum, a drum against which the membrane is held securely by a strip of felt under tension or any other treatment sheet. In addition, it is also possible to combine a suitable support substrate with the membrane layer, if desired, and the support substrate can serve as a permanent support.

The liquophobic microporous membrane 151 must have sufficient liquophobicity with respect to the liquid to be treated so as to prevent the introduction of the liquid being treated into the membrane. On the other hand, the liquophilic microporous membrane 150 must have a sufficient pore size and liquophilicity relative to the liquid to be treated so as to be sufficiently wetted by the liquid to prevent the passage of gas after being wetted. Next a

- 14 embodiment, the liquophilic and liquophobic microporous membranes 150, 151 both have, when combined for use in the medium forming barriers to liquids, an overall pore size such that the membranes form a bacterial barrier. Advantageously, in particular in medical applications, the system is gamma-sterilizable.

The microporous membrane can be produced from various materials provided that the required properties of the particular porous medium are obtained. These are the resistance necessary to manipulate the differential pressures encountered during use and the ability to obtain the desired filtration capacity while obtaining the desired permeability without the application of excessive pressure. The porous medium can be, for example, a porous fibrous medium, such as a depth filter, or a membrane or a porous sheet. Multilayer porous media can be used, for example a porous multilayer membrane with one liquophobic layer and the other liquophilic.

Advantageous starting materials are synthetic polymers such as polyamides, polyesters, polyolefins, in particular polypropylene and polymethylpentene, perfluorinated polyolefins, such as polytetrafluoroethylene, polysulfones, polyvinylidene difluoride, polyacrylonitrile, etc., and mixtures of compatible polymers. The most advantageous polymer is polyvinylidene difluoride. In the class of polyamides, the preferred polymers are polyhexamethylene adipamide, poly-e-caprolactam, polymethylene sebaçamide, poly-7-aminoheptanoamide, polytetramethylene adipamide (Nylon 46) and polyhexamethylene azeleamide, polyhexamethylene adipamide (Nylon 66 ) being the most

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- 15 advantageous. Hydrophilic polyamide membranes, essentially insoluble in alcohols, without skin, such as those described in US-A-4340479, prove to be particularly advantageous.

Other starting materials can also be used to form the porous media of the present invention, including cellulose derivatives, such as cellulose acetate, cell propionate, cellulose acetopropionate, cellulose acetobutyrate and cellulose butyrate. It is also possible to use non-resinous materials, such as glass fibers.

It will be noted that if the material chosen is normally liquophobic, and it is desirable to use this material for the liquophilic microporous membrane, the normally liquophobic material must then be treated so as to make it liquophilic. The nature of the material used to manufacture the membranes and the compatibility of the materials chosen for the membranes with respect to each other and with respect to the liquid to be treated are also factors to be considered in the choice of the particular materials for membranes for a given final application. However, quite apart from these considerations, it may be desirable to use the same material for the microporous and liquophilic membrane and for the liquophobic microporous membrane so as to facilitate the connection of the two different membranes to each other. , as required, if this proves advantageous.

The advantageous materials used as microporous and liquophilic membrane and microporous and liquophobic membrane are respectively nylon and polyvinylidene difluoride. Since polyvinylidene difluoride is liquophobic, it must be treated in order to make it liquophilic. Various treatments for normally liquophobic polyvinylidene difluoride are known

- 18 may include one or more media forming a barrier to liquids.

It will be obvious to those skilled in the art that the plasma of a liquid barrier medium can be optimized to achieve a desired result. For example, it may be desirable to position the liquid barrier medium as close as possible to junction 125, for practical use reasons. According to a more advantageous embodiment, a clamp can be positioned between the medium forming a barrier to liquids 124 and the junction 125, as exemplified in FIG. 4.

As seen in Figure 2, the assembly includes four clamps. The first clamp 130 is provided in the conduit 113 between the first container 111 and the junction 125. The second clamp 131 is provided between the functional biomedical device 115 and the junction 126 and the third clamp 132 is provided between the junction 126 and the second container 112. Finally, a fourth clamp 133 is provided in the conduit 122 between the junction 126 and the third container 121. According to another embodiment, as shown in FIG. 4, the clamp 160 is placed on the conduit 113 between the junction 125 and the functional biomedical device 115. The clamp 161 is placed on a conduit between the medium forming a barrier to liquids 124 and the junction 125. A clamp 132 is provided between the junction 126 and the second container 112, and a clamp 133 is provided on the conduit between the junction 126 and the third container 121. The use of the pliers shown in Figure 2 is described below.

The recovery of the various elements of the treatment assembly can be maximized.

The envelope can be made of a rigid plastic which is also transparent, such as polyethylene, an acrylic material such as oS3oüy ui

- 19 polymethyl methacrylate, polymethyl acrylate, polymethylpenthene-1, polyvinyl chloride and copolymers of vinyl chloride-vinylidene chloride. Translucent materials can also be used, such as polypropylene, polyethylene, urea-formaldehyde and melamine-formaldehyde polymers. Other plastics which are particularly suitable are polystyrene, polyamides, polytetrafluoroethylene, polyfluorotrichlorethylene, polycarbonates, polyester, phenol-formaldehyde resins, polyvinyl butyral, cellulose acetate, cellulose acetopropionate , ethyl cellulose and polyoxymethylene resins. Polyacrylonitrile-polybutadiene-styrene (ABS) are preferred. It is understood that the invention should not be limited by the type of envelope used. Other materials may be used as well as mixtures, combinations and / or copolymers of any of the above materials.

You can use a metal casing. Suitable metals are stainless steel alloys, such as nickel, chromium, vanadium, molybdenum and manganese alloys. The envelope material must obviously be inert vis-à-vis the treated liquids.

The containers which are used in the blood processing assembly can be made of any material compatible with whole blood or blood products, and must be able to withstand centrifugation and a sterilization environment. A wide variety of these containers is already known in practice. For example, blood and satellite collection bags are typically made from plasticized polyvinyl chloride, for example PVC plasticized with dioctyl phthalate, diethylhexyl phthalate or trioctyl trimellitate.

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The bags can also be formed from a polyolefin, a polyurethane, a polyester or a polycarbonate.

The assembly described above in accordance with Figure 2 is used as follows. Movement of blood or blood product through the assembly is accomplished by maintaining a pressure difference between the first container 111 and the destination of the blood or blood product. Examples of means for establishing this pressure difference can be constituted by a gravity column, the application of pressure to the collection bag (for example manual or with a pressure sleeve) or by the placement of the second container. 112 in a chamber which establishes a pressure difference between the first container 111 and the second container 112 (for example a pressure chamber).

Once the pressure difference is established and the clamps 130, 131 and 133 are open and the clamp 132 is closed, a column of blood product is brought through the conduit 113, by the functional biomedical device 115, into the conduit 114, until the product reaches junction 126. As the blood product advances, it pushes the gas in the conduit in front of it until the gas reaches junction 126. At the junction 12 6, the gas in front of the blood product moves in the gas collection and displacement loop 120. Once all the gas has passed through the loop 120, the clamp 133 is then closed, the clamp 132 is open and the biological fluid flows into the second container or the transfer bag 112.

The gases which pass through the gas collection and displacement loop 120 are collected in the third container 121 and returned to the system in the form of a purge gas to facilitate the

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- 21 recovery of the biological fluid which is retained in the various elements of the system. This is accomplished as follows.

After the treatment of the blood in the collection bag 111, the clamp 132 is closed, and the third container 121 is compressed to bring the gas into the container 121 in the form of a purge gas into the system through the conduits 123 and 113. The gas passes through the medium forming a barrier to liquids 124 in the conduit 123 and then passes through the conduit 113 in the first container 111. After opening the clamp 132, the gas coming from the first container 111 will then move any biological product remaining in the first container 111, the conduit 113 and the functional biomedical device 115 to the second container 112. Optionally, the first container 111 can be pressed to facilitate recovery.

Once the recovery is complete, the clamp 131 can be closed, the clamp 13 3 can be opened and the second container 112 can be pressed in order to remove any trace of gas from the second container 112. At the end of the separation of the gas from the second container 112, the clamp 132 must be closed.

According to another embodiment, the assembly comprises a pre-primed functional biomedical device.

Note that, although the third container 121 is described above as being formed of a flexible bag, the container 121 may be a rigid container. In addition, although the third container 121, the liquid barrier medium 124 and the means for closing the loop (the fourth clamp 133) are described above as being formed separately, they can be formed as a single unit.

Obviously, the air in the second container 112 can be eliminated by closing the clamp 131 and

- 22 opening the clamps 132 and 133. The second container 112 can then be pressed in any of the ways described above, to pass air through the conduit 114 into the conduit 122 and from there into the container 121 From the container 121, the air can be brought into the container 111, as described above in the context of FIG. 2.

According to another embodiment shown in FIG. 4, comprising a medium forming a barrier to liquids 124 and a third container 121 (hereinafter the gas collection or displacement bag), a functional biomedical device 115 can be connected to a second container 112 and a gas collection and displacement loop 120 can be connected upstream and downstream of the functional biomedical device. The gas collection and displacement loop can be connected using Y connectors upstream 125 and downstream 126 of the functional biomedical device 115. The gas collection and displacement loop comprises a gas collection and displacement bag 100 cc 121 and an envelope containing a medium forming a barrier to liquids. The envelope and the liquid barrier medium form an assembly forming a liquid barrier 124. The assembly forming a barrier to liquids is arranged inside the gas collection and displacement loop in a conduit between the manifold Y 125 upstream of the functional biomedical device 115 and the gas collection and displacement bag. The medium forming a barrier to liquids comprises a liquophobic membrane produced according to international patent application No. WO 91/17809. The assembly forming a barrier to liquids was also carried out according to international patent application No. WO 91/17809.

There may be a clamp 160 on the conduit between the upstream of the functioning biomedical deviceθθόΟΟ ^ οΐ

- 23 nel 115 and the collector 125, as well as a clamp 161 on the conduit between the collector 125 upstream of the functional biomedical device and the medium forming a barrier to liquids. There may also be a clamp 133 on the conduit between the gas collection and displacement bag 121 and the collector downstream of the functional biomedical device 126, as well as a clamp 132 on the conduit between the downstream of the functional biomedical device and the satellite bag 112. This clamp 132 can be located downstream of the manifold 126 which connects the downstream of the functional biomedical device to the gas collection and displacement loop.

The clamps 160, 161, 133 and 13 2 can be closed and the first container can be connected to the conduit upstream of the functional biomedical device. The functional biomedical device can be placed vertically. The clamps 160 and 132 can be opened and the blood product can be expressed from the first container ill through the functional biomedical device 115 in the second container or satellite container 112 until the first container is emptied. The gas can be displaced by the blood product in the second container. The clamp 160 can then be closed.

The gas harvesting and moving bag 121 can be lifted and the clamp 133 must be opened. The elevation of the gas collection bag can allow the flow of an additional quantity of blood product in the conduit downstream of the functional biomedical device in the satellite container. Once the fluid has drained, the clamp 133 can be closed and the gas collection and displacement bag can be lowered. Then, the satellite container 112 should be handled until the gas concentrates on the side of the top of the satellite container. The clamp 133 must then be opened while continuing to compri09J0Ü3U1

- 24 sea the satellite bag to expel the gas from the satellite container in the gas collection and displacement bag 121. Once the gas has been expelled, the clamp 133 must be closed.

The gas collection and displacement bag 121 can be manipulated until the gas is concentrated on the side of the top of the gas collection bag and the tube. The clamp 161 can be opened and the gas can be brought into the conduit upstream of the functional biomedical device and possibly in the first container, and the clamp 161 can then be closed. The clamp 160 can then be opened, which can displace or expel a certain amount of the blood product retained in the functional biomedical device and / or the conduit downstream of the functional biomedical device. This displaced blood product can be recovered in the satellite container 112 without collecting gas, since the functional biomedical device 115 will not be completely emptied.

The clamp 132 must then be closed and the tube on the outlet side of the functional biomedical device must be closed.

It should be understood that the present invention is in no way limited to the above embodiments and that many modifications can be made without departing from the scope of this patent.

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