HK1065730A - Manual processing systems and method for providing blood components conditioned for pathogen inactivation - Google Patents

Description

Manual processing systems and methods for providing blood components conditioned for pathogen inactivation

Technical Field

The present invention relates generally to the processing of whole blood and its components for storage, fractionation and transfusion.

Background

Clinically validated components of whole blood include, for example, red blood cells, which can be used to treat chronic anemia; plasma, which can be used as a blood volume expander or which can be fractionated so as to obtain coagulation factor VIII-rich condensed proteins for the treatment of haemophilia; and platelet concentrates, which are useful for controlling thrombocytopenic hemorrhage.

As the demand for these blood components increases, the demand for purity of the blood product also increases. It is desirable to minimize the amount of impurities or other substances that may cause adverse side effects in a recipient prior to storing blood components, such as red blood cells or platelets, for later transfusion.

For example, it is generally considered desirable to remove leukocytes from such blood components prior to storage or at least prior to transfusion. It is also advantageous to inactivate potential blood-borne pathogens (e.g., free viruses and bacteria) in blood components prior to transfusion, for example, by using a photosensitizing chemical reaction or a non-photosensitizing chemical reaction.

Summary of The Invention

The present invention provides systems and methods for manually processing blood and blood components in a sterile, closed environment, and for conditioning the blood components for subsequent pathogen inactivation. The system and method provide an optional novel system and method that matches the manual collection of random donor platelet units with the production of larger therapeutic doses of platelets that are pathogen inactivated prior to long term storage and/or transfusion.

Drawings

FIG. 1 is a blood processing system that mixes a platelet additive solution (additive solution) into a platelet component in a complete sterile closed system to condition the platelet component for pathogen inactivation;

FIGS. 2A and 2B are kits for pooling random donor units of platelet components pre-mixed with a platelet additive solution;

FIG. 3 is a blood processing system which mixes a platelet additive solution into a platelet component in an intact sterile closed system and filters the mixture to remove leukocytes, thereby conditioning the platelet component in a leukocyte-reduced state for pathogen inactivation;

FIG. 4 is another embodiment of a blood processing system that mixes a platelet additive solution into a platelet component in an intact, sterile closed system and filters the mixture to remove leukocytes, thereby conditioning the platelet component in a leukocyte-reduced state for pathogen inactivation;

FIG. 5 is a blood processing system similar to FIG. 4 which mixes a platelet additive solution into the platelet component in an intact sterile closed system and filters the mixture to remove leukocytes, thereby conditioning the platelet component in a leukocyte-reduced state for pathogen inactivation and also filtering the red blood cell component (mixed with an additive solution) to remove leukocytes;

FIG. 6 is a kit for pooling random donor units of platelet components while mixing a platelet additive solution with the pooling units to condition the pooling units for pathogen inactivation;

fig. 7 to 9 are views of alternative embodiments of a pooling container that may be incorporated into the pooling kit shown in fig. 2A/2B or fig. 6 and that increases the amount of residual red blood cells separated and removed from the pooled platelet components;

FIG. 10A is an exploded perspective view of a filter for removing white blood cells from a platelet component and a red blood cell component, which filter may be used with the system shown in FIGS. 2 through 6;

FIG. 10B is an assembled perspective view of the filter of FIG. 7A;

FIG. 11 is a schematic diagram of a blood processing system and associated methods that provide platelet components collected in a sterile, closed system in the form of random donor units that are conditioned, individually or in pooled units, for pathogen inactivation;

FIG. 12 is a system that performs the functions of the system and method shown in FIG. 11 by mixing a pooled dose of platelet components preconditioned for pathogen inactivation with a pathogen-inactivating compound to form a pooled dose ready for treatment;

FIG. 13 is a perspective view of a device that performs the functions of the system and method of FIG. 11, namely pathogen inactivation of a pooled dose of platelet components to be treated;

FIG. 14 is a schematic view of another blood processing system and associated methods that process platelet components collected in the form of random donor units in a sterile closed system and condition them for pathogen inactivation while they are combined into a large therapeutic dose;

FIG. 15 is a schematic view of a blood processing system and associated methods that provide red blood cells collected in a sterile closed system, the red blood cells being conditioned for pathogen inactivation; and

fig. 16 is a side view of a centrifuge cup that houses a pooling container of the type shown in fig. 7 when centrifuged to separate residual red blood cells from pooled platelet components.

The invention is not limited to the specific constructions and arrangements of parts so described and illustrated in the drawings. The invention may be practiced in other embodiments and in various ways. The terms and phrases used herein are for descriptive purposes only and are not to be construed as limiting.

Description of the preferred embodiments

FIG. 1 illustrates a manually operated blood collection and storage system 10 having features of the present invention. The system 10 is a disposable, dedicated system.

The system 10, when sterilized, can form an integral sterile "closed" system, as measured by applicable standards. In the united states, blood storage procedures are subject to government regulations. The maximum storage life of blood components collected in these systems is particularly specified. For example, in the united states, according to government regulations, whole blood components collected in "open" (i.e., non-sterile) systems must be transfused to recipients within twenty-four hours, most often within six to eight hours. In contrast, whole blood components collected in a "closed" (i.e., sterile) system may be stored in a defined refrigerated environment for up to forty-two days (depending on the type of anticoagulant and storage medium employed), plasma may be stored frozen for longer periods of time, and platelet concentrates may be stored at room temperature for up to five days.

The system 10 includes a main blood processing container 12. In use, the main container 12 receives a unit of whole blood for centrifugation through the feeding tube 26 and the lancet 28 integrally connected thereto. In the embodiment shown in fig. 1, main container 12 is filled with a suitable anticoagulant, such as CPD.

The system 10 also includes at least one transfer vessel 14 integrally connected to the main vessel 12 by a series of flexible transfer tubes 20. In use, the transfer container 14 receives one of the blood components separated in the main container 12 by centrifugation. Preferably, the transfer container 14 also serves as a storage container for a blood component at the end of the treatment process.

The system 10 also includes at least one additive solution container 18 integrally connected to the main container 12 by a flexible transfer tubing string 20. The additive solution container 10 contains an additive solution for the blood components that are ultimately stored in the transfer container 14. In use, the additive solution mixes with the blood components at some point during the blood treatment process. The composition of the additive solution may vary depending on the blood component with which it is mixed.

Preferably, the transfer container 14 is used for storing a platelet fraction, in particular a platelet concentrate containing a residual amount of plasma, obtained by centrifuging a platelet-rich plasma.

Preferably, the concentration of platelets in container 14 is such that it is conducive to subsequent pathogen inactivation treatments. Accordingly, the solution container 18 preferably includes an additive solution 22 that specifically conditions the platelet concentrate for the pathogen inactivation treatment by a form, e.g., a desired viscosity and absorbance (to aid in transmitting light energy typically used for light-sensitive pathogen inactivation treatments) and/or a desired physiological condition, e.g., pH, that is conducive to effective pathogen inactivation. Preferably, the additive solution 22, after pathogen inactivation treatment, also allows for the conditioning of platelet concentrates for long-term storage by providing an appropriate mixture of nutrients and buffers for maintaining platelet metabolism during storage.

To accomplish this, the additive solution 22 contained in the solution container 18 preferably includes a synthetic medium for use in conjunction with pathogen inactivation of platelets. The synthetic medium comprises an aqueous solution (e.g., a phosphate buffered saline solution) other than a natural fluid (e.g., plasma, serum, etc.). The synthetic medium is added to a platelet concentrate, which optionally contains residual amounts of plasma, so that after treatment, the platelet concentrate remains in a mixture of the synthetic medium and plasma. Depending on the particular composition of the medium 22, it may be desirable to have a predetermined ratio between the medium 22 and the residual plasma in the mixture.

In a preferred embodiment, the ideal mixture of synthetic medium 22 and plasma conditions the platelet concentrate to be suitable for pathogen purification in the presence of a desired amount of a pathogen-inactivating compound added to the mixture of platelet concentrate and additive solution after treatment in system 10. The pathogen-inactivating compound may comprise a nucleic acid binding mixture, preferably selected from the group consisting of furocoumarins. In a preferred embodiment, the furocoumarin is a psoralen that is activated by a photosensitizing device, see, for example, U.S. Pat. Nos. 578,736 and 5,593,823. Most preferably, the psoralen comprises 5 '- (4-amino-2-oxa) butyl-4, 5' 8-trimethylpsoralen (also known as s-59) present at a concentration of about 100 μ g/ml or less.

For pathogen inactivation, the preferred concentration of s-59 in the platelet concentrate is about 50 μ g/ml or less.

Psoralens are tricyclic compounds formed by linear fusion of a furan ring with a coumarin. Psoralens can intercalate between base pairs of double-stranded nucleic acids by absorbing long-wave Ultraviolet (UVA) light to form pyrimidine covalent adducts. Additional details of photosensitive mixtures that may be included in the additive solution are described in U.S. patent No. 6,251,580, which is incorporated herein by reference.

The photosensitizing device for activating psoralen as described above emits a spectrum of electromagnetic radiation of a given intensity, with wavelengths between 180 nm and 400 nm, in particular between 20 nm and 380 nm. Preferably, the intensity is less than 25 megawatts per square centimeter (e.g., between 10 and 20 megawatts per square centimeter), and the mixture is exposed to the intensity for one to twenty minutes (e.g., ten minutes).

Synthetic media 22, optionally mixed with plasma, regulates bloodPlatelet concentrates, making them suitable for use in other pathogen inactivation systems that employ other types of pathogen inactivation compounds. For example, other pathogen inactivation compounds that may be employed by other pathogen inactivation systems include: a phthalocyanine derivative; phenothiazine derivatives (including methylene blue or dimethyl methylene blue); endogenous and exogenous photosensitizers, e.g. alloxazines, isoalloxazines (including riboflavin), vitamin K₈Vitamin L, naphthoquinone, naphthalene, naphthol, and the like, and other pathogen inactivating compounds are disclosed in U.S. patent nos. 6,358,577, 6,368,120, and 6,277,337, which are incorporated herein by reference, and pathogen mixtures may also include "pen 110", manufactured by v.i. technologies, inc^TMCompound(s).

In one representative embodiment (e.g., using s-59), the synthesis medium 22 comprises an aqueous solution having about: 45-120mM sodium chloride; 5-15mM sodium citrate; 20-40mM sodium acetate; and 20-40mM sodium phosphate. In a preferred embodiment, the aqueous solution comprises: about 70 to 90mM sodium chloride; about 8 to 12mM sodium citrate; about 25-35mM sodium acetate; and about 22-35mM sodium phosphate, which can be a combination of various protonated sodium phosphate species, e.g., disodium hydrogen phosphate and sodium dihydrogen phosphate. The solution has a pH of from about 7.0 to 7.4, preferably about 7.2. Since glucose or magnesium is not present, the medium can be easily autoclaved.

A preferred composition of solution 22 is prepared by:

sodium chloride: 77.3mM

Sodium acetate 3H₂O：32.5mM

Sodium citrate 2H₂O：10.8mM

Sodium dihydrogen phosphate 1H₂O：6.7mM

Anhydrous disodium hydrogen phosphate: 31.5mM

The solution may be formulated at 99% of the target concentration in order to maintain shelf life, i.e., to counteract water evaporation during storage. Moreover, when the above formulation is the initial formulation, the ratio of acid to conjugate base of certain ingredients may vary due to pH changes and/or adjustments. Such changes may alter the initial formulation during preparation and/or storage.

With this formulation, it is preferred that the platelet additive solution 22 be mixed with the residual plasma in the platelet concentrate in a ratio of 50% to 80% by volume of the additive solution (the remainder being plasma). The preferred ratio is 60% to 70% by volume of the additive solution (the remainder being plasma). The most preferred ratio is about 65% by volume of the additive solution and about 35% by volume of plasma. When other pathogen-inactivating compounds and/or different agents 22 are used, different volume ratios of synthetic medium 22 to plasma may be used to optimize pathogen inactivation.

Preferably, the apparatus 10 further includes another solution storage container 16 integrally connected to the main container 12 as part of a flexible transfer tubing string 20. The additive solution container 16 contains an additive solution 24, the additive solution 24 being different from the platelet additive solution 22 in the container 18. The other additive solution 24 is used to mix with a blood component other than a platelet suspension.

For example, the other additive solution may be specifically formulated to mix with red blood cells, thereby acting as a storage medium. One such solution is disclosed in U.S. Pat. No. 4,267,369 to Grode et al, which is sold by Baxter Healthcare Corporation under the trade name ADSOL  solution. Other examples include SAGM solution or CPDA-1 solution. The additive solution may be selected to condition the red blood cells for pathogen inactivation treatment. For example, an additive solution of the type known as Erythrosol (also known as E-Sol or related solution E-Sol A) can be mixed with red blood cells, thereby rendering them suitable for pathogen inactivation treatment. E-Sol includes sodium citrate (25 mM); disodium phosphate (16.0 mM); sodium dihydrogen phosphate (4.4 mM); adenine (1.5 mM); mannitol (39.9 mM); and glucose (45.4 mM). E-Sol can be added to red blood cells as two separate components, E-Sol A and glucose solution. E-Sol A comprises sodium citrate (26.6 mM); disodium hydrogen phosphate (17.0 mM); sodium dihydrogen phosphate (4.7 mM); adenine (1.6 mM); mannitol (42.5 mM). The pH of E-Sol and E-Sol A is in the range of 7.0 to 7.5, preferably in the range of 7.3 to 7.5. The concentration of the above components may vary within the range of ± 15% of the concentration.

Preferably, when the solution 24 in the additive solution container 16 is empty, the container 16 is capable of storing another blood component that is neither a platelet suspension nor a blood component that is mixed with another additive solution 24. In the system 10, the solution container 16 may contain a platelet poor plasma component, which is a by-product of the centrifugation of platelet rich plasma to produce a platelet concentrate.

Although not explicitly shown, it is understood that the system 10 of FIG. 1 includes a conventional external clamp and an in-line frangible cannula, which are operated in a conventional manner to control the flow of fluid within the system 10, as is well known to those of ordinary skill in the blood processing arts. The flexible tubing array 20 also includes a conventional in-line Y-branch connector or T-branch connector for the transfer tubing.

The vessels and transfer tubes associated with the systems shown in figure 1 can be made of any proven flexible medical grade conventional plastic material, such as polyvinyl chloride (PVC-DEHP) plasticized with di (2-ethylhexyl) phthalate. Such containers are manufactured using conventional heat sealing techniques such as high frequency heat sealing (RF) and the like. However, the transfer container 14, which serves as a storage container for the platelet suspension, is preferably made of the following materials: blow molded polyolefin materials (as disclosed in U.S. patent No. 4,140,162 to Gajewshi et al), or heat sealable polyvinyl chloride materials (TEHTM) plasticized with tris (3-ethylhexyl) trimellitate, or blends of: styrene-ethylene-butylene-styrene (SEBS) block copolymers (e.g., KRATON  G-1652M), Ethylene Vinyl Acetate (EVA), and Ultra Low Density Polyethylene (ULDPE) manufactured by Baxter healthcare Corporation under the designation PL-2410. These materials have better gas permeability than DEHP plasticized polyvinyl chloride materials, facilitating the storage of platelets.

As described above, the system 10 can achieve at least two processing objectives. The first objective is to process one unit of whole blood to obtain Red Blood Cells (RBCs), a platelet concentrate component (PC), and a platelet poor plasma component (PPP) in an integrated sterile closed system. A second objective is to condition the PC component in a unitary sterile closed system for pathogen inactivation treatment and for other treatments such as long term storage, and/or pooling (pooling), or a combination of these treatments.

In this arrangement, the platelet additive solution 22 in container 18 also serves as a resuspension solution for the PC component in storage container 14. This causes more PPP to be released for collection. Thus, the system 10 also maximizes PPP recovery.

In use, after the main container 12 receives whole blood from a donor, the donor tubing 26 and lancet 28 are disconnected from the rest of the system 10. Separation of the donor vessel 22 may be accomplished by forming a snap-fit seal within the donor vessel 26 using a conventional heat sealing device, such as the Hematron  dielectric sealer sold by Baxter healthcare Corporation. Whole blood is mixed with an anticoagulant.

The whole blood is then centrifuged in the main container 12 into red blood cells (RBC component) and platelet rich plasma (PRP component). During processing, heavier PBC components collect at the bottom of the main vessel 12 and lighter PRP components collect at the top of the main vessel 12. Upon centrifugation, a buffy coat is typically formed between the RBC component and the PRP component.

After centrifugation, the PRP component is expressed from the main container 12 and transferred to the transfer container 14 through the tube array 20. A conventional V-shaped plasma press may be used for this purpose. This extrusion is preferably monitored to maintain as much of the intermediate layer and white blood cells contained therein, as well as RBC components, in the container 12 as possible.

The solution 24 in the additional solution container 16 may be transferred to the RBC constituent in the main container 12. Thus, the first additive solution is mixed with the RBC component.

The main container 12 may be separated from the rest of the assembly by forming a quick-disconnect seal using a conventional dielectric seal as previously described. Of course, the RBC component can then be subjected to further processing, such as leukocyte filtration (as will be described in detail below) and/or pathogen inactivation.

The PRP component is then centrifuged in container 14 to separate a majority of the platelets from the plasma, thereby producing a PC component and a PPP component.

The PPP composition may be expressed from the transfer container 14 and transferred through the tubing string 20 to the first additive solution container 16 (which is now empty). A conventional V-shaped plasma press as described above may be used for this purpose. The desired residual amount of PPP component remains in the transfer container 14 along with the PC component. The first additive solution container 16 containing the PPP components extruded from container 14 can be separated from the rest of the system 10 by forming a quick-disconnect seal using a conventional dielectric sealing device as previously described. As with the RBC component, the PPP component can then be further processed, e.g., cell filtered, and/or pathogen inactivated, and/or frozen to form frozen fresh plasma for storage and/or fractionation.

Platelet additive solution 22 can be transferred from addition container 18 to transfer container 14 through tubing array 20. The platelet additive solution 22 is mixed with the PC component and plasma in the preferred volumetric proportions, as previously described. The additive solution reservoir 18 may be disconnected from the rest of the assembly by forming a quick-disconnect seal using a conventional dielectric sealing device as previously described.

As with the RBC component and PPP component, the PC component mixed with the plasma and additive solution 22 can then be further processed, such as leukocyte filtration, and/or pathogen inactivation, and/or stored, and/or pooled, or a combination of these processes. For example, as shown in fig. 2A, a desired number of containers 14, each containing one unit of PC component premixed with the plasma and platelet additive solution 22, may be connected to a pooling kit (kit) 44. The pooling kit 44 combines platelets from multiple random donor units (random donor units) with platelets scheduled for therapeutic dosing for transfusion.

The pooling kit 44 includes one pooling container 40, the container 40 being connected to a series of multi-tube conduits 42. A six-tube catheter 42 is shown in fig. 2A, which allows six pooling of multiple random donor units of PC components pre-mixed with plasma and platelet additive solution 22 in container 40. This is because therapeutic doses of platelets typically include six manual donor units. Of course, a fewer or greater number of conduits 42 may be provided, as the case may be.

A given container 14 may be individually connected to a given one of the conduits 42 in a variety of ways. For example (as shown in fig. 2A), a closed tube segment or attachment 140 may be attached to container 14 by aseptic docking techniques, as disclosed in Spencer U.S. patent No. 4,412,835 or Granzow et al U.S. patent nos. 4,157,723 and 4,265,280, both of which are incorporated herein by reference. In this arrangement, the connection is not made to communicate with the atmosphere. Thereby forming a substantially sterile connection. As a result, the storage time of the PC component in the merge container 40 may reach the maximum allowable storage time.

Alternatively, a non-sterile connection may be used, such as inserting a conventional blood needle into a port of the container 18 (not shown). However, this connection technique is open to the atmosphere. Therefore, the merged PC component must be quickly transmitted according to local government regulations. On the other hand, if the pooled PC fractions are subjected to pathogen inactivation treatment, the institution regulating blood collection and/or processing activities may someday allow for extended storage time of pooled PC fractions collected from an open system. In this case, the above-described pooling kit does not necessarily comprise a closed blood processing system.

As shown in fig. 2B, in addition to being connected to the merge vessel 40 by conduit 42 (shown in fig. 2A), the vessels 14 may also be connected in series to the merge vessel 40, an arrangement also referred to as "stringing". In this embodiment, each container 14 includes a tube portion or appendage 140 that is closed at both the top and bottom. The bottom portion 140 of the upper container 14 is connected to the top portion 140 of the next lower container 14, and so on, to form a string, wherein the connection is preferably by the sterile docking technique described above. The PC component, premixed with plasma and additive solution 22, is discharged through a chain of interconnected containers 14 forming a string into a combining container 40.

Regardless of whether the vessels 14 are connected in parallel (FIG. 2A) or in series (FIG. 2B), the pooling assembly 44 may include a suitable in-line leukoreduction filter 43, preferably located adjacent the inlet of the pooling vessel 40. This arrangement accomplishes the leukocyte filtration of the PC component premixed with the plasma and platelet additive solution 22 during the pooling of multiple random donor units. In this arrangement, the bypass branch 46 preferably extends around the leukocyte filter. Bypass branch 46 allows for compression of air from merge vessel 40. The manifold also allows for more complete emptying, thereby maximizing recovery of pooled, filtered platelets. Preferably, bypass branch 46 is provided with a one-way valve V to allow fluid flow only in the direction of container 14, preventing fluid flow in the opposite direction.

Because each PC component unit (i.e., the PC component collected and processed in container 14) already contains plasma and platelet additive solution 22, the pooled units in container 40 can be adjusted for pathogen inactivation. Because the platelet additive solution 22 has been mixed with the PC components in a closed, integrated system, there is no need to later (e.g., during subsequent combining) provide a sterile connection for each PC component to receive the additive solution 22.

Alternatively, if desired, each unit (in container 14) may be individually subjected to pathogen inactivation treatment prior to or in lieu of the pooling treatment.

Thus, the system 10 provides a single random donor PC component unit for manual processing that can be processed for pathogen inactivation in a time-saving and economical manner. The system 10 is capable of providing PC components suitable for pathogen inactivation processes without relying on automated methods.

As shown in fig. 2A, the consolidation kit 44 optionally includes a storage container 48 connected to the consolidation container 40 by a transfer tube branch 50. The reservoir container 48 allows the pooled platelet PC components to be centrifuged again in the pooling container 40 to again remove red blood cells, thereby producing a more pure platelet product suspended in the platelet additive solution. After centrifugation, the pooled platelet components may be extruded (using, for example, a V-press) from the pooling container 40 into the storage container 48 in the presence of the additive solution 22, while carefully leaving the separated residual red blood cells in the pooling container 40 (e.g., by visual monitoring or electrical interface detection techniques). Thus, a conditioned pooled platelet fraction suitable for pathogen inactivation treatment can be provided, and the fraction is substantially free of red blood cells. Residual red blood cells may be further separated from the pooled platelet components in the pooling container 40 by other means, as will be described in more detail below.

In an alternative arrangement (shown in phantom in fig. 2A/2B), the transfer line branch 50 may also include a suitable in-line leukoreduction filter 52, with a suitable exhaust bypass branch 54 and one-way valve V. Filter 52 may be used in conjunction with filter 43 to secondarily remove leukocytes from the pooled platelet components. Filter 52 may be used in place of filter 43 to first reduce leukocytes.

The leukocyte-reduced platelet component units, pre-mixed with plasma and additive solution 22 in a closed system, may be processed prior to being combined. The system 10 itself may achieve leukopenia of each PC component unit prior to pooling, either before or after mixing with the platelet additive solution 22 as shown in fig. 3 and 4. In this arrangement, the multi-conduit kit 40 (shown in FIG. 2A) provided for combining the individual units of PC components need not have a leukoreduction filter or similar leukoreduction function.

As an example shown in FIG. 3, the branch line 60 between the delivery container 14 and the additive solution container 18 may include a suitable inline leukoreduction filter 64. The bypass branch 62 extends around the leukocyte filter.

A one-way valve V may also be provided in the bypass branch 62 to allow fluid flow only toward the container 14, preventing fluid flow in the opposite direction.

In use, after the PPP component in the container 14 has been transferred away, the platelet additive solution 22 may be transferred from the container 18 to the container 14 through the bypass branch 62 to mix with the plasma and PC components. After mixing is complete, the PC component, plasma, and additive solution 22 may be transferred through leukoreduction filter 64 into container 18. Residual air may be discharged from vessel 18 into vessel 14 through bypass branch 62. In this arrangement, the additive solution container 18 ultimately serves as a storage container for the reduced leukocyte PC component after mixing with the plasma and platelet additive solution 22.

Of course, the PC component and plasma may be delivered directly from the container 14 through the filter 64 without prior delivery of the additive solution 22 for mixing with the PC component. In this arrangement, the PC component and plasma are mixed with the additive solution as they enter container 18. Further, it is preferred that the PC component and plasma be mixed with the platelet additive solution 22 prior to passing them through the leuko-filter 64. By pre-mixing the PC component with the additive solution 22, it is not necessary to manually agitate the mixture of PC component, plasma and additive solution after filtering the leukocytes. Mixing also reduces the viscosity of the PC component, resulting in an overall increase in flow rate during leukocyte filtration, and mitigates platelet destruction or mobilization during processing.

In another example as shown in fig. 4, a transfer pipe branch 66 may be provided between the transfer container 14 and a further transfer container 68. The delivery tube branch 66 may include a suitable in-line leukoreduction filter 72. The bypass branch 70 preferably extends around a leukoreduction filter 72. A one-way valve V may also be provided in the bypass branch 70 to allow fluid flow only toward the container 14 and to prevent fluid flow in the opposite direction.

In use, after the PPP component in container 14 has been transferred to container 16, the platelet additive solution 22 may be transferred to container 14 for mixing with the PC component and residual plasma, as previously described. After mixing is complete, the PC component, plasma and additive solution 22 may be transferred through the transfer line branch 60 through the leukoreduction filter to the transfer container 68. Residual air may be discharged from the tank 68 to the tank 14 through a bypass branch 70. In this arrangement, the container 68 ultimately serves as a storage container for the reduced leukocyte PC component mixed with the plasma and platelet additive solution 22.

Alternatively, as shown in phantom in fig. 4, in addition to being connected to container 14 by tube 60, additive solution container 18 may be connected directly to transfer container 68 to transfer additive solution 22 into transfer solution container 68 before, during, or after the PC component and plasma pass through filter 72. Alternatively, the platelet additive solution 22 may be stored in the container 68 for mixing with the PC component and plasma when performing the leukopheresis. Also, as described above, it is preferable that the additive solution 22 is mixed with the PC component before the leukocyte filtration is performed.

In another preferred embodiment (see FIG. 5), the system 10 may also provide an on-line leukopenia function for other blood cell components, i.e., red blood cells. In this arrangement, the system 10 further comprises a second transfer vessel 30, the second transfer vessel 30 being connected to the main vessel 12 by a flexible transfer tube branch 32 and a flexible tubing string 20. An in-line leukoreduction filter 34 is provided on the transfer line branch 32. It is also preferred that a bypass branch 36 with a non-return valve V is provided for the exhaust gases. Blood samples may also be collected in the bypass manifold 36. A one-way valve (not shown) may be provided in the branch 36 to allow fluid flow only in the direction of the container 12 and to prevent fluid flow in the opposite direction. The filter 34 for the red blood cell component may be used in the system 10 with the filter 72 for the platelet component shown in fig. 5, or the filter 64 for the platelet component shown in fig. 3. Alternatively, the filter 34 for the red blood cell component may be used alone in the system 10 without the filter 72/64 for the platelet component.

The method of operation of the system 10 shown in fig. 5 is substantially the same as the method of operation of the system 10 shown in fig. 1. In contrast, after the additive solution 24 is transferred to the RBC constituent in the main container 12, the RBC constituent mixed with the additive solution 24 is transferred through transfer tube branch 32 to container 30 through filter 34. Residual air in the tank 30 is discharged into the main tank 12 through the bypass branch 36. The container 30 serves as a storage container for the leukocyte-reduced RBCs. By pre-mixing the red blood cell components with the additive solution 24, it is not necessary to manually agitate the red blood cell additive solution after filtering the white blood cells. Mixing also reduces the viscosity of the red blood cells, resulting in an overall increase in flow rate during leukocyte filtration, so that hemolysis does not occur during processing. However, it should be understood that it is preferred to mix the red blood cell additive solution 24 with the red blood cells after the white blood cells have been filtered for other reasons. In this arrangement, the container holding the additive solution 24 may be directly and integrally connected to the second transfer container 30.

The operation of random donor PC composition has been described previously, and is formed at the beginning of the separation of platelet concentrate, which is derived from platelet rich plasma. However, it should be understood that whole blood may be centrifuged at a relatively high centrifugation speed (also referred to as "hard spin") in the main container 12. The hard spin forces a large number of platelets out of the plasma and into the middle buffy coat layer, which forms between the plasma and red blood cell components upon centrifugation. In this arrangement, the PC component comprises one platelet-rich random donor buffy coat unit. Additive solution 22 may be added to condition platelets in the platelet rich buffy coat of a random donor in a manner substantially the same as and to the same advantageous effects as previously described for pathogen inactivation in a closed, sterile blood processing system. The conditioned platelets can be collected from the buffy coat for pathogen inactivation by centrifuging a desired number of the conditioned pooled random donor buffy coat units. This centrifugation separates residual red blood cells and white blood cells from the platelets prior to the pathogen inactivation treatment. It will be appreciated that the number and arrangement of containers in a given blood processing system may vary depending on the purpose for which the blood is being processed.

Fig. 6 shows an alternative embodiment of a pooling kit 80 for PC components that have not been mixed with the platelet additive solution 22 at the time of primary processing. In this arrangement, a consolidation kit 80 includes a consolidation receptacle 82 connected to a series of multi-tube conduits 84. Seven tubes of conduits 84(1) to 84(6) are shown in fig. 6. The six conduits 84(1) through 84(6) allow for the pooling of six containers 86 in container 12, each container containing one random donor unit of PC component (and the desired amount of plasma) that is not mixed with the platelet additive solution 22. A seventh conduit 84(7) allows platelet additive solution 22 to be added from container 88 at the beginning of the pooling. As previously described, each of the containers 86 and 88 may be connected to one of the conduits 84 by a sterile or non-sterile docking technique. Alternatively, the container 88 containing the additive solution 22 may be integrally connected to the cartridge 80 at the time of manufacture.

Of course, as previously described, the pooling kit 80 may include more or less than seven catheters, depending on the starting number of random donor platelets and the desired treatment dosage. An interconnected chain of containers 86 forming a "string" (shown in fig. 2B, replacing container 14) may also be used to transfer the PC component mixed with plasma into the combining container 82. In this arrangement, the platelet additive solution 22 (in container 88) is preferably connected to the pooling container 82, as shown in phantom in fig. 2B, to mix the solution 22 with the string-combined PC components.

As shown in FIG. 6, the pooling kit 80 may include a suitable in-line leukoreduction filter 90 preferably positioned between the junctions of all of the conduits 84 and the pooling container 82. For venting purposes, a bypass branch 98 with a non-return valve V is also preferably provided in this arrangement, as previously described. In this arrangement, leukocyte filtration of the PC component is accomplished while mixing the PC component with the platelet additive solution 22, all during the process of pooling multiple random donor units.

Referring also to fig. 6, optionally, the consolidation kit 80 may further include a storage container 92 connected to the consolidation container 82 by a transfer tube branch 94. Transfer line branch 94 may include a suitable in-line leukoreduction filter 96 (with bypass branch 97 and one-way valve V) (shown in phantom in fig. 6) either in conjunction with filter 90 or in place of filter 90. This arrangement may be used if it is desired to separate residual red blood cells from the PC component in the combining container 82 after combining, for example, by centrifugal separation or gravity sedimentation, as described in the context of the combining kit 40 shown in fig. 2A/2B. The platelet component may then be transferred from the pooling container 82 into the container 92 (via, for example, a V-press) while carefully leaving the separated residual red blood cells in the pooling container 82 (e.g., via visual monitoring or electrical interface detection techniques). In this way, a pooled platelet fraction is provided that is conditioned for pathogen inactivation treatment and is substantially free of red blood cells.

In the pooling kits 40 and 80 shown in fig. 2A and 6, respectively, additional means may be provided to separate residual red blood cells separated from the pooled platelet components in the pooling container from the platelet components, thereby providing pooled platelet components that are both conditioned for pathogen inactivation and substantially free of red blood cells.

For example, as shown in FIG. 7, a pooling kit 80A of the type shown in FIG. 6 (which may also include a pooling kit of the type shown in FIGS. 2A/2B) includes a pooling container 120, with a bottom region of the container 120 being tapered to form a reduced volume, red blood cell collection area 122. As shown in fig. 7, the shape and size of the region 122 is defined by a heat seal formed on the wall of the container 120. Alternatively (not shown), a preformed molded or extruded structure can be heat sealed to the bottom of the container 120 to form the reduced volume, red blood cell collection region 122.

The red blood cells may be caused to settle by gravity into the reduced volume region 122 of the combining vessel 120. The presence of the platelet additive solution 22 may enhance the gravity sedimentation process. Alternatively, the pooling container 120 may be centrifuged wherein the region 122 is oriented toward a high gravity field (high-G field) so that residual red blood cells centrifuged from the platelet component will be collected by centrifugal force in the reduced volume region 122.

When centrifugation is employed, the merge container 120 is preferably placed in a centrifuge cup, which is sized and shaped to receive and support the reduced volume region 122 within a high gravity field. The centrifuge cup may be constructed and arranged in a variety of ways.

In the exemplary embodiment shown in fig. 16, the centrifuge cup 340 includes an interior chamber 342. The inner cavity 342 accommodates the unitizing vessel 122 (shown in phantom in fig. 16) for rotation on a centrifuge rotor (not shown). The centrifuge cup 340 includes a hinge 348 to open the interior 342 in a clamshell fashion (as indicated by arrow 350) to facilitate loading of the container 120.

Still referring to fig. 16, the bottom of the interior chamber 342 (facing the high gravity field as the centrifuge rotor rotates) includes a pocket 344. The pocket 344 is shaped and sized to receive the reduced volume region 122 of the container 120 (shown in phantom in fig. 16). Upon centrifugation, the reduced volume region 122 is contained in a well 344 in a high gravitational field, collecting the residual red blood cells. One or more alignment pins 336 are provided in the housing in the cavity 332 to mate with alignment holes 338 (see fig. 7) formed in the merge container 120 to further stabilize and support the reduced volume region 122 in the pocket 334.

Once centrifugation (or gravity settling) is complete, a clamping device 124 or similar device (shown in phantom in fig. 7) seals the region 122 from the remainder of the vessel 120. As shown in fig. 7, the region 122 preferably forms an attachment that is not attached to the container 120 along its side edges, which facilitates the positioning of the clamping device 124 and minimizes the required clamping area. The clamping device 124 forms a seal across the region 122 that mechanically separates residual red blood cells in the pooling container 120 from the PC component. The merge container 120 is then processed with the gripper 124 in place. Alternatively, the seal across region 122 may be formed by a high frequency seal, thus eliminating the need for external clamping device 124. Alternatively, as shown in dashed lines in fig. 7, the platelet component (substantially free of red blood cells) may be extruded into an attached storage container 92 (e.g., by a V-press). Because of the use of the clamping device 124, there is no need to use manual or electrically assisted interface detection techniques.

In another embodiment shown in fig. 8, a merge kit of the type shown in fig. 6 (merge kit 80B may also comprise a merge kit of the type shown in fig. 2A/2B) includes a merge container 126, with a top region 128 of the container 126 being tapered. During centrifugation of the pooling container 126, the region 128 is oriented toward a low gravity field (low-G field), so that residual red blood cells centrifuged (or gravity settled) from the platelet component are collected in a lower (high gravity) region of the container 126. Once centrifugation or sedimentation is complete, the pooled platelet components are expressed out through the tapered upper region 128 into the storage container 92. The reduced volume upper region 128 reduces the interface for separating red blood cells to a smaller area. This allows for easy visual or electrical detection of the interface and controls the delivery of components such that red blood cells are substantially prevented from entering the reservoir 92.

In another embodiment shown in fig. 9, a pooling kit 80C of the type shown in fig. 6 (which may also include a pooling kit of the type shown in fig. 2A/2B) includes a pooling container 130, the bottom region of the container 130 being generally conical, thereby forming a red blood cell collection region 132. A small volume red blood cell separation vessel 134 is connected to the red blood cell collection region 132 by a tube branch 136, wherein the tube branch 136 also has an in-line one-way valve 138. The one-way valve 138 allows fluid from the collection area 132 to flow toward the separation vessel 134 but not in the opposite direction. During centrifugation of the pooling container 130, the region 132 is oriented to a high gravitational field, and thus residual red blood cells centrifuged from the platelet component will be collected in the region 132. As previously mentioned, gravity settling may also be used. Once centrifugation (or sedimentation) is complete, residual red blood cells in region 132 are expressed through one-way valve 138 and tube branch 136 into separation vessel 134. After the desired residual amount of blood has been discharged into the separation vessel 134, the tube branch 136 is sealed and separated (e.g., by forming a quick-break seal using a conventional heat sealing device). This arrangement eliminates the need for an additional container 92, since the pooled platelet components in the pooling container 130 have been adjusted for pathogen inactivation and are substantially free of red blood cells.

In the described embodiment, filtration is used to remove leukocytes from blood components. However, it is to be understood that, from a technical point of view, the separation of leukocytes can be achieved by a variety of techniques, both centrifugal and non-centrifugal, not just by "filtration". Separation can be achieved by absorption, column, chemical, electrical and electromagnetic means. "filtration" is used in the present specification in a broad sense and also includes all such separation techniques.

The above leukocyte filter can be constructed in various forms. In the embodiment shown in fig. 10A and 10B, the filter F includes a housing 100, the housing 100 enclosing a filter media 102, which filter media 102 may be comprised of a film or fibrous material. The filter media 102 may be provided in a single layer or a multi-layer stack. If a fibrous material, the media 102 can include meltblown or spunbond synthetic fibers (e.g., nylon or polyester or polypropylene), semi-synthetic fibers, recycled fibers, or inorganic fibers. If a fibrous material is used, the media 102 is subjected to depth filtration to remove leukocytes. If a thin film is used, the medium 102 is "rejected" (exclusion) to remove leukocytes.

The housing 100 may comprise a rigid plastic plate with a peripheral seal. In the embodiment shown, the housing 100 includes first and second flexible sheets 104 made of a medical grade plastic material, such as polyvinyl chloride (PVC-DEHP) plasticized with di (2-ethylhexyl) phthalate. Other non-PVC and/or DEHP-free medical grade plastic materials may also be used.

In the embodiment shown, an integral continuous peripheral seal 106 is formed by applying pressure and high frequency heat to both flexible sheet 104 and filter media 102 in a single process (see FIG. 10B). The seal 106 bonds the two flexible sheets 104 together and bonds the filter media 102 to the two flexible sheets 104. The seal 106 unifies the material of the filter media 102 with the material of the plastic sheet 104 to form a reliable, strong, leak-proof boundary. Because the seal 106 is integral and continuous, blood is unlikely to flow out along the periphery of the filter media 102.

The filter F also includes an inlet and an outlet 108. Port 108 may comprise a tube made of a medical grade plastic material such as PVC-DEHP. In the embodiment shown in fig. 10A and 10B, the port 108 is formed by a separately molded piece that is heat sealed by high frequency energy to a port 109 formed in the plastic sheet 104 (see fig. 10A).

The systems and methods described above enable the processing of platelet components in a pathogen inactivation process, wherein the platelet components are manually collected as random donor platelet units in a sterile closed system, in order to meet the demand for large, therapeutic doses of platelet components. Typically, on-line automated processing systems and methods are employed to meet this need for larger therapeutic doses of pathogen inactivated platelet components. The above-described systems and methods provide new methods and systems that enable both manual collection of random donor platelet units and the production of large therapeutic doses of platelets that are pathogen inactivated prior to long-term storage and/or transfusion.

For example, as shown in FIG. 11, a system and associated method 200 may have a manual blood collection function 202. Function 202 processes blood drawn from a single donor 204. Function 202 may include the closed, sterile, manually-operated blood collection and storage system 10 shown in fig. 1 or 3 or 4 or 5.

Function 202 generates a random donor sterile platelet component unit 206. Unlike other random donor platelet units, the unit 206 produced by function 202 is conditioned for pathogen inactivation by mixing with plasma and a predetermined platelet additive solution 22 in a sterile closed system. The random donor sterile platelet component unit 206 is also suitable for long term storage if not treated for pathogen inactivation. The function 202 may also subject the random donor sterile platelet component units 206 to closed system leukocyte filtration processing, whereby the units 206 are conditioned in a reduced leukocyte state to accommodate pathogen inactivation processing and/or long term storage.

The function 202 may also generate a random donor sterile Red Blood Cell (RBC) unit 208 (which may also be subject to closed system leukocyte filtration) and/or a random donor platelet sterile plasma (PPP) component unit 210, one or both of which may be suitable for long-term storage and/or pathogen sterile processing, as will be described in greater detail below.

The system and method 200 also includes a merge function 212. The pooling function 212 receives a plurality of random donor sterile platelet component units 206 whose platelets have been conditioned by the previous function 202 to be suitable for pathogen inactivation. One unit 206 is received from a function 202 associated with a donor 204 and the remaining units 206 ' are received from similar functions 202 ' associated with other random donors 204 '. The merge function 212 may comprise a closed sterile, manually operated merge kit as shown in fig. 2 or 7 or 8 or 9.

Function 212 produces a pooled random donor sterile platelet component dose 214. Because each random donor sterile platelet component unit 206 contains plasma and the pre-mixed platelet additive solution 22, the dose 214 is adjusted to be suitable for pathogen inactivation. The pooled random donor sterile platelet component dose 214 is suitable for long term storage even without pathogen inactivation treatment. Function 212 may also subject the combined random donor sterile platelet component dose 214 to a closed system leukocyte filtration process such that the dose 214 is conditioned in a reduced leukocyte state to accommodate pathogen inactivation processes and/or long term storage. Function 212 may also subject the combined random donor sterile platelet component dose 214 to closed system centrifugation such that the dose 214 is substantially free of red blood cells and conditioned in the absence of red blood cells to be suitable for pathogen inactivation processing and/or long term storage.

The system and method 200 may also include a pathogen inactivating compound mixing function 216. The mixing function 216 receives the pooled random donor sterile platelet component doses 214 and mixes them with a predetermined amount of pathogen inactivating compound 218 (see fig. 12). As shown in fig. 12, such mixing is preferably accomplished in a sterile manner by attaching a closed tube portion 140 (see fig. 2A) on the merge-kit container 48 to a similar closed tube portion 140 on an in-line container 220 containing a pathogen-inactivating compound 218, using suitable sterile docking techniques (as described previously). If the merge-kit container 48 is not present (i.e., no red blood cell removal is performed during the merge function 212), the merge-kit container 40 may itself carry the tubing segment 140 for sterile docking. Mixing is accomplished by transferring the platelet component dose 214 from the pooling container 48 (or 40) through the in-line container 220 to the transfer container 232.

The mixing function 216 generates a merged random donor dose 222 that begins processing, which is stored in the transfer container 232 after mixing. The pooled random donor dose 222 at which processing was initiated is formed by mixing the pooled random donor sterile platelet component dose 214 with the pathogen inactivating compound 218 (see FIG. 11).

In the absence of the consolidation function 212, the pathogen inactivation compound 218 may be separately mixed with the random donor sterile platelet component units 206 (resulting from function 202) by sterile docking with the tube portion 140 on the transfer container 14 (see fig. 1 or 3) or on the transfer container 68 (see fig. 4 or 5). In this arrangement, the random donor sterile platelet component unit 206 can be pathogen inactivated in the next function 224.

The system and method 200 also includes a pathogen inactivation function 224. The pathogen inactivation function 224 receives the pooled random donor dose 222 (now contained in container 232) to begin processing. By virtue of the functionality of the pathogen inactivation compound 218, the pathogen inactivation treatment may be performed in the container 232 without further stimulation. When further stimulation, such as photoactivation, is desired, the pathogen inactivation function 224 exposes the dose 222 to the additional stimulation required in the pathogen inactivation treatment.

In one embodiment, function 224 (see FIG. 13) may include associating the combined random donor dose 222 (contained in container 232) to begin processing with device 226 having electromagnetic radiation source 228. The radiation source 228 provides electromagnetic radiation of an appropriate wavelength to cause activation of the pathogen inactivating compound 218, which in this arrangement is a photoreaction. The device 226 may support one or more doses 222 in a fixed relationship with the radiation source 228, and otherwise control the operation of the photoactivation treatment. Details regarding the apparatus for performing the light inactivation function are shown in U.S. patent No. 5,593,823, which is incorporated herein by reference.

The pathogen inactivation function 224 produces a pooled random donor platelet dose 230 that is pathogen free. Once the residual pathogen inactivating compound 218 is removed (e.g., by contact with an absorbing medium 234 contained in another transfer vessel 236, wherein the transfer vessel 236 is connected to a container 232 (see fig. 12)), the pooled platelet dose 230 free of pathogens is suitable for long-term storage and/or transfusion. As shown in fig. 12, the pooled platelet dose 230 without pathogens may be transferred to a storage container 238, the storage container 238 being connected to the transfer container 234. As shown in fig. 12, the in-line container 220 (containing the light-inactivating compound 218), the transport container 232 (in which pathogen inactivation occurs), the transport container 236 (in which the pathogen-inactivating compound 218 is removed), and the storage container 238 (in which the pooled platelet dose 230 without pathogens is ultimately stored) may constitute a complete sterile system 240 that is connected to the pooled container when pathogen inactivation is desired.

As shown in FIG. 15, the random donor sterile Red Blood Cell (RBC) unit 208 (which has undergone closed system leukocyte filtration) can itself be conditioned by the blood collection function 202 to be suitable for pathogen inactivation by mixing in a sterile closed system with a defined red blood cell additive solution 24 as described above (see, e.g., FIG. 1). This provides a random donor sterile red blood cell component unit 306 that is also suitable for long term storage without pathogen inactivation. The function 202 may also perform closed system leukocyte filtration of the random donor sterile red blood cell component units 306, as previously described (see, e.g., FIG. 5), such that the units 306 are conditioned in a reduced leukocyte state suitable for pathogen inactivation processes and/or long-term storage. The red blood cell units 306 may be conditioned for pathogen inactivation simultaneously with or separately from the platelet concentrate.

In this arrangement, as shown in fig. 15, a pathogen inactivating compound mixing function 316 is also provided. The mixing function 316 receives the conditioned red blood cell units 306 and mixes them with a desired amount of pathogen-inactivating compound 318 for the red blood cells. Examples of pathogen-inactivating compounds for inactivation of red blood cell pathogens include those previously described, as well as those disclosed in U.S. patent No. 6,093,725, which relates to the use of compounds having nucleic acid affinity, including the mustard cluster or mustard cluster equivalents, or mustard cluster intermediates, and pending U.S. patent application serial No. 09/539,226 filed on 3/30/2000. U.S. patent No. 6,093,725 and U.S. patent application No. 09/539,226 are incorporated herein by reference. A preferred pathogen-inactivating compound for pathogen-inactivation of erythrocytes is N- (acridin-9-yl) -p-alanine 2- [ bis (2-chloroethyl) amino ] ethyl ester (p-alanine, N- (acridin-9-yl), 2- [ bis (2-chloroethyl) amino ] ethyl ester). The red blood cell units 308 and compounds 318 are preferably mixed in a sterile manner, for example, in the manner previously described in connection with the platelet component dose 214. The mixing function 216 produces a starting red blood cell unit 322.

In this arrangement, the pathogen inactivation function 324 receives the red blood cell units 322 that begin processing. Depending on the function of the pathogen-inactivating compound 318, the pathogen-inactivating treatment may be performed without further stimulation or by exposing the dose 214 to additional stimuli required for the particular pathogen-inactivating treatment. The pathogen inactivation function 324 provides a pathogen free red blood cell unit 330.

Fig. 14 illustrates another system and associated method 300. It can be conditioned on manually collected random donor platelet units for pooled pathogen inactivation treatment. In FIG. 14, the system and method 300 includes a combined merge and adjust function 302. The combinatorial function 302 receives a plurality of random donor platelet units 304 generated from individual donors 204 through a conventional manual blood processing function 306, wherein the conventional manual blood processing function 306 does not make adjustments to the units 304 to make them suitable for pathogen inactivation processes. The combining function 302 combines these random donor units 304 in a closed system while adding the defined platelet additive solution 22 to condition them in a combined state for pathogen inactivation treatment. Thus, function 302 produces a pooled random donor sterile platelet component dose 214 having the same features as previously described in connection with method 200 of FIG. 11. The merge function 302 may comprise a closed sterile manually operated merge kit as in fig. 6 or 7 or 8 or 9.

Because the platelet additive solution 22 has already been mixed at the time of combining, the dose 214 produced by function 302 is adjusted to be suitable for pathogen inactivation treatment. The pooled random donor sterile platelet component dose 214 is suitable for long term storage even without pathogen inactivation treatment. The function 302 may also incorporate a random donor sterile platelet component dose 214 for closed system leukocyte filtration processing, whereby the dose 214 is conditioned for pathogen inactivation processing and/or long term storage in a reduced leukocyte state. Function 302 may also perform closed system centrifugation of the pooled random donor sterile platelet component dose 214 such that the dose 214 is substantially free of red blood cells and is conditioned in the absence of red blood cells to render it suitable for pathogen inactivation and/or long term storage.

As shown in fig. 14, the method 300 may include a subsequent pathogen inactivating compound mixing function 216 to produce a ready-to-process (treatment-ready) pooled random donor dose 222 and may include a subsequent pathogen inactivating function 224 to produce a pathogen-free pooled random donor platelet dose 230. Functions 216 and 224, and the resulting platelet doses 222 and 230, have the same features as previously described in connection with fig. 11.

The foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation illustrated and described. Although preferred embodiments have been described, changes may be made in detail without departing from the invention as defined in the appended claims.

Claims (50)

1. A platelet concentrate unit comprising:

the container is sealed, and the sealing device is arranged in the container,

a platelet concentrate mixture in a sealed container, the platelet concentrate mixture comprising a platelet concentrate volume, a plasma volume, and a synthetic platelet additive solution volume,

the platelet concentrate volume and plasma volume are collected from a unit of whole blood drawn from a single donor and processed for centrifugation in a sterile closed blood collection system that includes the sealed container, and

the volume of synthetic platelet additive solution is mixed with a volume of platelet concentrate and a volume of plasma in the sterile, closed blood collection system, the volume of synthetic platelet additive solution including some of the following components: these components can be used to condition the platelet concentrate mixture for pathogen inactivation treatment in the presence of selected pathogen inactivating compounds.

2. Platelet concentrate units according to claim 1,

wherein the sealed container includes an appendage sized and configured to be coupled to tubing to transport the platelet concentrate mixture from the sealed container to a selected destination.

3. Platelet concentrate units according to claim 2,

wherein the appendage is connected to the conduit to form a substantially sterile connection.

4. Platelet concentrate units according to claim 1,

wherein the volume of platelet concentrate is filtered in the sterile closed blood collection system to be in a leukoreduced state.

5. Platelet concentrate units according to claim 1,

wherein the ingredients comprise an aqueous solution comprising sodium chloride, sodium citrate, sodium acetate, and sodium phosphate.

6. Platelet concentrate units according to claim 1,

wherein the selected pathogen-inactivating compound is selected from psoralen, methylene blue, dimethyl methylene blue, riboflavin, or PEN110, or combinations thereof.

7. A platelet pooling assembly comprising:

a manifold configured and dimensioned for transporting a plurality of platelet concentrate mixtures from a plurality of platelet concentrate units as defined in claim 1;

a container connected to the manifold for combining the plurality of platelet concentrate mixtures.

8. A platelet pooling assembly according to claim 7,

wherein the container includes an appendage sized and configured to connect the container to the source of the selected pathogen-inactivating compound.

9. A platelet pooling assembly according to claim 7,

it also includes a filter for removing leukocytes from platelets.

10. A platelet pooling assembly comprising:

a manifold configured and dimensioned for transporting a multiplexed platelet mixture from a plurality of platelet concentrate units as defined in claim 1;

a first container connected to the manifold for combining the plurality of platelet concentrate mixtures, and

a second container connected to the first container, the second container receiving the multi-channel platelet concentrate mixture after centrifugation in the first container to remove residual red blood cells.

11. A platelet pooling assembly according to claim 10,

wherein the second container includes an appendage sized and configured to connect the second container to the source of the selected pathogen-inactivating compound.

12. A platelet pooling assembly according to claim 10,

it also includes a filter for removing leukocytes from platelets.

13. A platelet pooling assembly comprising:

a first container for receiving a platelet concentrate, and

a second container integrally connected to the first container by tubing for receiving the platelet concentrate after centrifugation in the first container to remove residual red blood cells.

14. A platelet pooling assembly according to claim 13,

wherein the first container includes a reduced volume region for collecting residual red blood cells.

15. A platelet pooling assembly according to claim 13,

wherein the first container includes a reduced volume region for concentrating residual red blood cells.

16. A platelet pooling assembly according to claim 13,

a third container is also included, integrally connected to the first container by tubing, for receiving the separated residual red blood cells.

17. A platelet pooling assembly according to claim 16,

a one-way valve is also included in the conduit between the first container and the third container to prevent fluid flow from the third container to the first container.

18. A platelet pooling assembly according to claim 13,

wherein the tubing carries an in-line filter for removing leukocytes from platelets.

19. A platelet pooling assembly comprising:

a manifold configured and dimensioned to receive multiple platelet concentrate units centrifuged from a single random donor, the manifold further comprising a site for receiving a reconstituted platelet additive solution for mixing with the multiple platelet concentrate units, and

a container coupled to the manifold for combining the plurality of platelet concentrate units and the mixture of synthetic platelet additive solutions.

20. A platelet pooling assembly according to claim 19,

wherein the synthetic platelet additive solution volume includes some of the following: these components can be adjusted to make the multiple platelet concentrate units suitable for pathogen inactivation treatment in the presence of the selected pathogen inactivation compound.

21. A platelet pooling assembly according to claim 20,

wherein the ingredients comprise an aqueous solution comprising sodium chloride, sodium citrate, sodium acetate, and sodium phosphate.

22. Platelet concentrate units according to claim 20,

wherein the selected pathogen-inactivating compound is selected from psoralen, methylene blue, dimethyl methylene blue, riboflavin, or PEN110, or combinations thereof.

23. A platelet pooling assembly according to claim 20,

wherein the container includes an appendage sized and configured to connect the container to the source of the selected pathogen-inactivating compound.

24. A platelet pooling assembly according to claim 19,

it also includes a filter for removing leukocytes from platelets.

25. A platelet pooling assembly according to claim 19,

it also includes a second container connected to the first container by a tube for receiving the residue after the separation of the residual red blood cells.

26. A platelet pooling assembly according to claim 25,

it also includes a filter for removing leukocytes from platelets.

27. A manual blood collection system comprising:

a main container structured and dimensioned to hold a unit of whole blood for centrifugation drawn from a donor,

a platelet unit container structured and dimensioned to contain a platelet concentrate and a first volume of plasma centrifugally separated from the one unit of whole blood,

a plasma unit container constructed and dimensioned to contain a second volume of plasma centrifugally separated from the one unit of whole blood,

an auxiliary container structured and dimensioned to hold a synthetic platelet additive solution that, when mixed with the platelet concentrate and the first volume of plasma, produces a platelet concentrate mixture, the synthetic platelet additive solution including some of the following components: these components can be used to condition the platelet concentrate mixture for pathogen inactivation in the presence of selected pathogen inactivating compounds, and

tubing integrally connecting the primary container, the platelet unit container, the plasma unit container and the auxiliary container, thereby forming a sterile, closed blood processing system.

28. A manual blood collection system according to claim 27,

wherein the platelet concentrate mixture is contained in the platelet unit container after processing in the sterile, closed blood processing system.

29. A manual blood collection system according to claim 28,

wherein the platelet unit container includes an appendage shaped and dimensioned for coupling to a transfer line to transfer the platelet concentrate mixture from the platelet unit container to a selected destination.

30. The manual blood collection system of claim 29,

wherein the appendage is connected to the transfer conduit to form a substantially sterile connection.

31. A manual blood collection system according to claim 27,

wherein the platelet concentrate mixture is contained in the auxiliary container after processing in the sterile, closed blood processing system.

32. A manual blood collection system according to claim 31,

wherein the auxiliary container includes an appendage shaped and dimensioned for coupling to a transfer line for transferring the platelet concentrate mixture from the auxiliary container to a selected destination.

33. The manual blood collection system of claim 32,

wherein the appendage is connected to the transfer conduit to form a substantially sterile connection.

34. A manual blood collection system according to claim 27,

wherein the tubing carries an in-line filter for removing leukocytes from platelets.

35. A manual blood collection system according to claim 27,

wherein the ingredients comprise an aqueous solution comprising sodium chloride, sodium citrate, sodium acetate, and sodium phosphate.

36. A manual blood collection system according to claim 27,

wherein the selected pathogen-inactivating compound is selected from psoralen, methylene blue, dimethyl methylene blue, riboflavin, or PEN110, or combinations thereof.

37. A manual blood collection system according to claim 27,

further comprising a red blood cell unit container constructed and dimensioned to contain red blood cells centrifuged from the whole blood of the unit, and

wherein the tubing integrally connects the main container, the platelet unit container, the plasma unit container, the red blood cell unit container and the auxiliary container to form a sterile closed blood processing system.

38. A manual blood collection system according to claim 37,

wherein the plasma unit container contains an additive solution for mixing with red blood cells.

Closed system leukocyte filtration.

50. In accordance with the system of claim 48,

also includes a device for closed system leukocyte filtration of the random donor sterile platelet component units.

51. In accordance with the system of claim 48,

also included is a means for mixing the pooled random donor sterile platelet component doses with a desired amount of a pathogen inactivating compound to provide pooled random donor doses ready for processing.

52. In accordance with the system of claim 51,

also included is a means for pathogen decontamination processing of the pooled random donor doses ready for processing.

53. A method for collecting random donor platelet units conditioned for pathogen inactivation treatment, comprising the steps of: random donor sterile platelet component units are collected from a unit of whole blood drawn from a single donor and centrifuged in a sterile closed blood collection system, conditioned for pathogen inactivation by mixing with a defined platelet additive solution in the sterile closed blood collection system.

54. According to the method of claim 53, wherein,

also included is the step of performing closed system leukocyte filtration of the unit of random donor sterile platelet component.

55. According to the method of claim 53, wherein,

also included is the step of collecting at least one additional blood component from the unit of whole blood in the sterile, closed blood processing system.

56. A method for collecting pooled therapeutic platelet units conditioned for pathogen inactivation treatment from random donor platelet units, comprising the steps of:

collecting a unit of random donor sterile platelet component from a unit of whole blood, wherein the unit of whole blood is drawn from a single donor and centrifuged in a sterile closed blood collection system, the unit of random donor sterile platelet component conditioned for pathogen inactivation by mixing with a defined platelet additive solution in the sterile closed blood collection system, and

combining a plurality of random donor sterile platelet component units in a sterile closed system to provide a combined random donor sterile platelet component dose, wherein the combined random donor sterile platelet component dose is adjusted for pathogen inactivation due to the presence of the platelet additive solution.

57. In accordance with the method of claim 56,

also included is the step of performing a closed system leukocyte filtration of the pooled random donor sterile platelet component dose.

58. In accordance with the method of claim 56,

also included is the step of performing closed system leukocyte filtration of the unit of random donor sterile platelet component.

59. In accordance with the method of claim 56,

further comprising the step of mixing the pooled random donor sterile platelet component doses with a desired amount of a pathogen inactivating compound to provide pooled random donor doses ready for processing.

60. According to the method of claim 59, wherein,

further comprising the step of performing a pathogen decontamination process on the pooled random donor doses to be processed.

61. A method for collecting pooled therapeutic platelet units conditioned for pathogen inactivation treatment from random donor platelet units, comprising the steps of: