Compositions and methods for pathogen inactivation of platelets

Abstract

Compositions and methods for pathogen inactivation of platelets are provided, particularly methods, kits and compositions for preparing platelet compositions suitable for infusion, including improved methods, compositions and kits for pathogen inactivation of platelet preparations obtained by apheresis.

Description

[0001] This application is a divisional application of a patent application with application number 201880070298.X, application date September 20, 2018, and invention name “Compositions and methods for inactivating pathogens of platelets”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Patent Application No. 62 / 616,338 filed on January 11, 2018, U.S. Provisional Patent Application No. 62 / 586,739 filed on November 15, 2017, and U.S. Provisional Patent Application No. 62 / 561,157 filed on September 20, 2017, and the entire disclosure of each of the provisional patent applications is incorporated into this specification by reference. Technical Field

[0004] The present disclosure provides methods, kits and compositions for preparing platelet compositions suitable for transfusion.In some aspects, the present disclosure provides improved methods, kits and compositions for pathogen inactivation of platelet preparations, including apheresis-derived platelet preparations. Background Art

[0005] The collection and processing of blood components plays a vital role in global healthcare, and blood banks collect millions of units of donated blood components every year. Although some units of whole blood are collected from donors and used directly for transfusion, most donations are usually separated into blood components (red blood cells, platelets and plasma) for more specific therapeutic use. If a suitable separation device system is used, such as a single blood component collection device, separation can be performed after or during the collection of whole blood donations. The individual blood components are then used to treat different medical needs and conditions based on treatment needs.

[0006] Platelets play a key role in hemostasis, clot stability and retraction, as well as vascular repair and antimicrobial host defense. Various methods are used to collect and store platelet blood products for clinical use. Platelet collections from donated whole blood donations are typically in the form of platelet concentrates (PCs), obtained using processing methods such as buffy coat or platelet-rich plasma methods. Platelets are also obtained from apheresis collection, which uses an automated device that separates donor platelets from donor blood and returns remaining blood components (e.g., red blood cells and plasma) to the donor during the donation process.

[0007] In order to minimize the risk of infection of individuals receiving infected blood products, it is important to ensure that blood products, such as platelets, do not contain pathogens. The presence of blood pathogens tested is limited by the pathogens tested and the sensitivity of the assay. As an alternative or supplement to pathogen detection, it is known in the art to use a method for inactivating pathogens based on different compounds (e.g., chemistry, photochemistry) inactivation methods (e.g., as disclosed in Schlenke et al., Transfus Med Hemother, 2014, 41, 309–325 and Prowse, Vox Sanguinis, 2013, 104, 183–199). Such inactivation methods may need to specify a specific protection band range for the platelet volume and platelet number input to achieve the desired compound concentration for pathogen inactivation. For example, the minimum concentration can be defined by the concentration required to achieve a certain level of pathogen inactivation, and the maximum concentration can be defined by the concentration at which treatment can have an impact on the function of the treated blood products. Donation volumes and platelet counts can vary significantly from donor to donor or donation to donation, and to maximize the use of pathogen inactivation systems for blood component donations, increased processing flexibility remains desirable. The present specification describes methods, kits, and compositions for achieving increased flexibility and improved productivity in processing.

[0008] All references cited in this specification, including patent applications and publications, are incorporated by reference. Summary of the invention

[0009] In one aspect, a method for preparing a platelet composition (e.g., a pathogen-inactivated platelet composition) is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen-inactivating compound (PIC); (b) mixing the solution of step (a) with a platelet preparation; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, a method for preparing a platelet composition (e.g., a pathogen-inactivated platelet composition) is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen-inactivating compound (PIC) in a first container; (b) mixing the solution of step (a) with a platelet preparation; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition.

[0010] In some embodiments, providing a solution comprising PAS and PIC in a first container comprises first merging a PAS solution and a PIC solution to obtain a solution comprising PAS and PIC. In some embodiments, the method comprises merging a PAS solution and a PIC solution before step (a) to obtain a solution comprising PAS and PIC. In some embodiments, the solution of PAS comes from a PAS container (e.g., a PAS storage container). In some embodiments, the solution of PIC comes from a PIC container (e.g., a PIC storage container). In some embodiments, the solution of PAS and the solution of PIC are merged in the first container of step (a). In some embodiments, the first container of step (a) is a PAS container. In some embodiments, the first container of step (a) is a PIC container. In some embodiments, the solution of PAS and the solution of PIC are merged less than 24 hours (e.g., within 24 hours) before the mixing of step (b). In some embodiments, the mixing of step (b) occurs in the first container. In some embodiments, the mixing of step (b) occurs in the second container. In some embodiments, the mixing occurs in two or more second containers. In some embodiments, platelet preparations are prepared by apheresis. In some embodiments, the method further comprises connecting the first container to the apheresis device before step (b). In some embodiments, the PAS container is connected to the apheresis device. In some embodiments, the PIC container is connected to the apheresis device. In some embodiments, the second container is connected to the apheresis device. In some embodiments, two or more second containers are connected to the apheresis device. In some embodiments, the platelet preparation is prepared from one or more whole blood donations by the buffy coat method or the platelet-rich plasma (PRP) method. In some embodiments, the method further comprises transferring the platelet composition to a third container after step (c). In some embodiments, the method further comprises transferring the platelet composition to two or more third containers after step (c). In some embodiments, the third container comprises a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing platelet compositions. In some embodiments, the method further comprises transferring the platelet composition from the third container to one or more fourth containers. In some embodiments, one or more fourth containers are suitable for storing platelet compositions.

[0011] In some embodiments, the solution of step (a) has a volume of about 100 mL to about 1000 mL. In some embodiments, the solution of step (a) comprises a PIC at a concentration of about 15 μM to about 1500 μM. In some embodiments, the solution of step (a) comprises a PIC at a concentration of about 15 μM to about 235 μM. In some embodiments, the solution of step (a) comprises a PIC at a concentration of about 225 μM to about 235 μM. In some embodiments, the PIC is psoralen. In some embodiments, the PIC is amitosalin. In some embodiments, the platelet preparation comprises plasma, wherein the plasma comprises about 32-47% of the volume of the mixture of step (b), wherein the platelet additive solution (e.g., a platelet additive solution with PIC) comprises the remaining volume. In some embodiments, the ratio of PAS to plasma in the mixture of step (b) is about 65:35 by volume. In some embodiments, the total volume of the mixture of step (b) is about 100 mL to about 1000 mL. In some embodiments, the mixture of step (b) comprises PIC at a concentration sufficient to cause at least 1 log inactivation of the pathogen (if present). In some embodiments, the mixture of step (b) comprises PIC at a concentration sufficient to cause at least 3 log inactivation of the pathogen (if present). In some embodiments, the mixture of step (b) comprises PIC at a concentration sufficient to cause at least 4 log inactivation of the pathogen (if present). In some embodiments, the mixture of step (b) comprises PIC at a concentration of about 5 μM to about 500 μM. In some embodiments, the mixture of step (b) comprises PIC at a concentration of about 15 μM to about 150 μM. In some embodiments, the mixture of step (b) comprises PIC at a concentration of about 15 μM to about 30 μM. In some embodiments, the mixture of step (b) comprises PIC at a concentration of about 30 μM to about 150 μM. In some embodiments, the mixture of step (b) comprises PIC at a concentration of about 30 μM to about 90 μM. In some embodiments, the mixture of step (b) comprises PIC at a concentration of about 75 μM. In some embodiments, the mixture of step (b) comprises PIC at a concentration of about 145 μM to about 155 μM. In some embodiments, the PAS comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate. In some embodiments, the method further comprises incubating the mixture of step (b) for a period of 30 minutes to 24 hours prior to step (c). In some embodiments, the platelet composition comprises at least 2x10 11 Platelets.

[0012] In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens, and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing to remove residual PIC or its photoproduct. In some embodiments, the method is sufficient to inactivate at least 4 logs of pathogens, and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing to remove residual PIC or its photoproduct. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens, and wherein the platelet composition after step (c) is suitable for transfusion into a subject without transferring the platelet composition to a container containing a compound adsorption device (CAD). In some embodiments, the method is sufficient to inactivate at least 4 logs of pathogens, and wherein the platelet composition after step (c) is suitable for transfusion into a subject without transferring the platelet composition to a container containing a compound adsorption device (CAD). In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens, and wherein the platelet composition after step (c) contains 5 μM or less PIC. In some embodiments, the method is sufficient to inactivate at least 4 logs of pathogens, and wherein the platelet composition after step (c) comprises 5 μM or less of PIC. In some embodiments, the method is sufficient to inactivate at least 4 logs of pathogens, and wherein the platelet composition after step (c) comprises 2 μM or less (e.g., less than 2 μM) of PIC. In some embodiments, the method is sufficient to inactivate at least 4 logs of hepatitis E virus. In some embodiments, a platelet composition suitable for transfusion into a subject comprises about 5 μM or less of PIC. In some embodiments, a platelet composition suitable for transfusion into a subject comprises about 2 μM or less (e.g., less than 2 μM) of PIC. In some embodiments, the concentration of PIC in the mixture of step (b) is at least 10 μM. In some embodiments, the concentration of PIC in the mixture of step (b) is at least 30 μM.

[0013] In another aspect, a kit for preparing a platelet composition is provided, comprising: (a) a first container comprising a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing a platelet preparation mixed with a solution comprising PAS and PIC, wherein the first container is not connected to the second container.

[0014] In some embodiments, the first container is suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the second container is suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the second container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the first container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the kit further comprises a third container. In some embodiments, the third container comprises a compound adsorption device (CAD), and wherein the third container is connected to the second container. In some embodiments, the kit further comprises at least one storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the second container or to the third container, if the third container exists. In some embodiments, the kit does not contain a compound adsorption device (CAD).

[0015] In some embodiments, the solution comprising PAS and PIC has a volume of about 100 mL to about 1000 mL. In some embodiments, the PIC concentration is about 15 μM to about 1500 μM. In some embodiments, the PIC concentration is about 225 μM to about 235 μM. In some embodiments, the PIC is psoralen. In some embodiments, the PIC is amitosaline.

[0016] In some embodiments, the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or to a container containing a platelet preparation.

[0017] In another aspect, a kit for preparing a platelet composition is provided, comprising: (a) a first container comprising a platelet additive solution (PAS); (b) a second container comprising a pathogen inactivating compound (PIC); and (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC, wherein neither the first container nor the second container is connected to the third container. In some embodiments, the kit for preparing a platelet composition comprises a kit of components: (a) a first container comprising a platelet additive solution (PAS); (b) a second container comprising a pathogen inactivating compound (PIC); and (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC, wherein the first container and the second container are configured to be connected to each other, and wherein neither the first container nor the second container is connected to the third container. In some embodiments, a kit for preparing a platelet composition comprises a kit of the following components: (a) a first container comprising a platelet additive solution (PAS); (b) a second container comprising a pathogen inactivating compound (PIC); and (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC, wherein the first container and the second container are connected to each other, and wherein neither the first container nor the second container is connected to the third container. In some embodiments, the first container and the second container are connected to each other by a sealed but openable flow path (e.g., a frangible member, a frangible connector).

[0018] In some embodiments, the second container is suitable for merging PAS and PIC. In some embodiments, the second container is suitable for mixing platelet preparations with PAS and PIC. In some embodiments, the first container is suitable for merging PAS and PIC. In some embodiments, the first container is suitable for mixing platelet preparations with PAS and PIC. In some embodiments, the third container is suitable for mixing platelet preparations with PAS and PIC. In some embodiments, the third container is suitable for subjecting the platelet preparations mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is suitable for subjecting the platelet preparations mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the first container is suitable for subjecting the platelet preparations mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the third container comprises a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing platelet compositions. In some embodiments, the kit further comprises a fourth container. In some embodiments, the fourth container comprises a compound adsorption device (CAD), and wherein the fourth container is connected to the third container. In some embodiments, the kit further comprises at least one storage container, wherein the at least one storage container is suitable for storing a platelet composition, and wherein the at least one storage container is connected to the third container or to the fourth container, if the fourth container exists. In some embodiments, PIC is psoralen. In some embodiments, PIC is amitosalin. In some embodiments, the first container, the second container, or both the first container and the second container are suitable for connection to a single blood component device or to a container containing a platelet preparation. In some embodiments, the third container is suitable for connection to a single blood component device or to a container containing a platelet preparation. In some embodiments, the kit does not contain a compound adsorption device (CAD).

[0019] In another aspect, a composition comprising a pathogen inactivating compound (PIC) and a platelet additive solution (PAS) is provided, wherein the composition is platelet-free. In some embodiments, the concentration of the PIC is from about 15 μM to about 1500 μM. In some embodiments, the PIC is psoralen. In some embodiments, the PIC is amitosalin. In some embodiments, the PAS comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate. In some embodiments, the composition is sterile.

[0020] In another aspect, provided is a platelet composition prepared by any of the methods provided in this specification.

[0021] These and other aspects and advantages of the disclosed invention will become apparent from the following detailed description and the appended claims.It should be understood that one, some or all of the features of the various embodiments described in this specification may be combined to form other embodiments of the disclosed invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1A An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0023] Figure 1B An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0024] Figure 1C An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0025] Figure 1D An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0026] Figure 1E An exemplary kit for preparing a platelet composition is shown. The dashed line indicates the addition point for preparing the platelets.

[0027] Figure 2A An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0028] Figure 2B An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0029] Figure 2C An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0030] Figure 2D An exemplary kit for preparing a platelet composition is shown. The dashed lines indicate alternative addition points for the platelet preparation.

[0031] Figure 2E An exemplary kit for preparing a platelet composition is shown. The dashed line indicates the addition point for preparing the platelets.

[0032] Figure 3 A container containing a solution including a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) is shown connected to an exemplary apheresis device. DETAILED DESCRIPTION

[0033] In certain aspects, the disclosed invention provides improved methods, kits, and compositions for the inactivation of pathogens in platelet preparations, including apheresis-derived platelet preparations, for preparing platelet compositions suitable for transfusion.

[0034] The methods, kits and compositions disclosed in this specification relate to dosing a pathogen-inactivating compound (PIC), such as a photochemical compound, such as amitosalin, into a platelet preparation at a fixed concentration of pathogen-inactivating PIC. For example, the disclosed invention provides for premixing PIC with a desired (e.g., standardized) concentration of a platelet additive solution (PAS), and then dosing the PIC / PAS solution into a platelet preparation, thereby allowing, for example, (i) improved processing flexibility and control; (ii) improved inactivation of pathogens, including, for example, allowing for a reduction in the amount of PIC used for pathogen inactivation; (iii) reduced processing steps, for example, no need for further treatment using a compound adsorption device (CAD) to remove residual PIC or its photochemical products before administration to an individual; and / or (iv) improved platelet quality. Adding premixed PIC / PAS solutions in standard volumes of single, double and triple volumes, i.e., multiples of 1x, 2x and 3x, can help streamline both the collection process (e.g., via integration with platelet apheresis collection) and the processing process, so that, for example, the dose of all therapeutic pathogen inactivation of platelets in 65 / 35 PAS / plasma is the same regardless of whether they are derived from a single, double or triple donation and can always be treated with the same concentration of PIC.

[0035] Numerous benefits can be obtained through the improved methods, kits, and compositions disclosed in this specification, such as increased standardization of treatment conditions (which provides pathogen inactivation using more consistent PIC concentrations), elimination of some restrictive guard bands for platelet volume and / or platelet concentration input, greater flexibility in processing options available for pathogen inactivation of platelet preparations, and / or reduction in the amount of PIC required for pathogen inactivation. Thus, the disclosed invention can allow for much greater variation in the donation volumes processed. This, in turn, can also provide reduced variation in downstream processing steps (e.g., processing with a compound adsorption device (CAD)), and ultimately less variation in residual PIC in the final platelet product (e.g., a platelet composition).

[0036] In addition, the use of premixed PIC / PAS can provide the opportunity to manufacture and / or provide the PIC component separately from other components of the disposable processing kit or as a non-integrated component provided with the processing kit (e.g., as a kit), thereby significantly simplifying and reducing the equipment costs of the disposable kit associated with the manufacturing process. For example, the methods, kits, and compositions disclosed in the present specification can provide a processing kit with separate / unconnected "wet" side components (e.g., with PIC and PAS) and "dry" side components (e.g., lighting, CAD, and / or storage containers), thereby simplifying its manufacturing and sterilization risks.

[0037] In addition, the methods, kits, and compositions disclosed herein can allow for improved (e.g., increased) pathogen inactivation, e.g., in terms of the various types or species of pathogens inactivated and / or the extent to which a single type or species of pathogen is inactivated, and / or pathogen inactivation using reduced concentrations of PIC, e.g., by pre-incubating the PIC with a platelet preparation.

[0038] definition

[0039] " Platelet preparation " used in this application means a composition comprising platelets that have not been subjected to a pathogen inactivation process. In some embodiments, the platelet preparation is a platelet donation. In some embodiments, the platelet preparation is obtained from apheresis donations. In some embodiments, the platelet preparation is obtained from whole blood donations (e.g., by a buffy coat method, by a platelet-rich plasma (PRP) method). In some embodiments, the platelet preparation is obtained from more than one donor. In some embodiments, the platelet preparation comprises plasma.

[0040] "Pathogen inactivation process" used in this application means a process that can be used to inactivate pathogens that may be present in platelet preparations (such as platelet donations), wherein it should be understood that the process may not completely inactivate all pathogens that may be present, but substantially reduce the number of pathogens, thereby significantly reducing the risk of transfusion-related diseases. The inactivation of pathogens can be measured by measuring the number of infectious pathogens (e.g., viruses or bacteria) in a certain volume, and the inactivation level is typically expressed as a logarithmic reduction of pathogen infectivity or a logarithmic reduction of titer. The method for measuring the logarithmic reduction of titer and its measurement of pathogen inactivation are known in the art. For example, the method for measuring the logarithmic reduction of titer and its measurement of pathogen inactivation are described in U.S. Patent 7,655,392, because the patent relates to an assay method for pathogen inactivation, the disclosure is incorporated into this specification by reference. Thus, for any given pathogen, a known amount can be added to a test unit of platelets (e.g., a platelet preparation) to assess how much inactivation the process results, where typically a pathogen inactivation process produces at least about 1 log reduction in titer or about 2 logs, about 3 logs, about 4 logs, or at least about 5 logs or more reduction in titer. Although the methods described in this specification are applicable to any pathogen inactivation process, it is desirable that the pathogen inactivation process can inactivate a variety of pathogens to at least 1 log titer reduction, including pathogens selected from the group consisting of HIV-1, HBV, HCV, HTLV-1, HTLV-2, West Nile virus, hepatitis E virus, Escherichia coli, Klebsiella pneumoniae, Yersinia enterocolitica, Staphylococcus epidermidis, Staphylococcus aureus, Treponema pallidum, Borrelia burgdorferi, Plasmodium falciparum, Trypanosoma cruzi, and Babesia microti. In certain embodiments, the pathogen inactivation process may comprise treatment with a pathogen inactivating compound (PIC).

[0041] As used herein, "pathogen inactivating compound" or "PIC" means any suitable compound, such as a small organic compound, that can be used to inactivate pathogens and that can be present in platelet-containing blood products. "Photoactivated pathogen inactivating compound" is a suitable compound that requires a certain level of light in order to fully inactivate the pathogen (e.g., photochemical inactivation). Such compounds can be used to inactivate pathogens in platelets or other blood products because they provide control over the inactivation process. Such photoactivated pathogen inactivating compounds described in this specification include psoralens, isoalloxazines, alloxazines, phthalocyanines, phenothiazines, and porphyrins, wherein it should be understood that these terms include a large class of compounds, i.e., core compounds and suitable derivatives thereof. For example, psoralens or psoralens generally describe psoralen core compounds and any derivatives thereof (e.g., amitosalin), isoalloxazines or isoalloxazines generally describe isoalloxazine cores and any derivatives thereof (e.g., riboflavin), and so on. Such derivatives include the core compound structure as well as additional substituents on the core. The description of such compounds includes any salts thereof.

[0042] The term "aminosalin" as used in this application means the compound 3-(2-aminoethoxymethyl)-2,5,9-trimethylfuro[3,2-g]chromen-7-one and any salt thereof. The aminosalin compound may also be referred to as 3-[(2-aminoethoxy)methyl]-2,5,9-trimethyl-7H-furo[3,2-g][1]benzopyran-7-one-hydrochloride. The aminosalin compound may also be referred to as 4'-(4-amino-2-oxa)butyl-4,5',8-trimethylpsoralen. If the inactivation of a blood product, such as a platelet preparation, includes the addition of aminosalin HCl (aminosalin HCl salt) to the blood product, the removal of the compound from the blood product is not limited to the removal of aminosalin HCl, since aminosalin may be present in solution as other salts or as a free base.

[0043] As used herein, "platelet composition" means a pathogen-inactivated composition comprising platelets.

[0044] As used herein, "pathogen inactivated" describes a blood product (e.g., a platelet composition) that has undergone a pathogen inactivation process (e.g., by the methods described herein) to inactivate pathogens that may be present. It should be understood that the pathogen inactivation process does not necessarily completely inactivate all pathogens that may be present, but substantially reduces the amount of one or more pathogens, thereby significantly reducing the risk of transfusion-related diseases.

[0045] The term "suitable for transfusion" means any blood product (e.g., platelet composition, pathogen-inactivated platelet composition) that can be used for transfusion (e.g., transfusion) into a subject (e.g., a human patient) according to medical judgment. In some embodiments, suitability refers to having sufficient biological activity for its intended use, i.e., the use of coagulation factors suitable for transfusion, including, but not limited to, controlling bleeding associated with fibrinogen deficiency, treating factor XIII deficiency, treating factor VIII deficiency, treating von Willebrand disease, maintaining hemostasis, treating disseminated intravascular coagulation (DIC) or massive bleeding and / or causing fibrin adhesion. In some embodiments, suitability refers to having sufficient safety, such as the product has been treated to improve product safety (e.g., pathogen inactivation) and / or exhibits satisfactory performance in one or more safety-related measurements (e.g., viral or bacterial titer). The use of amitosalin and UVA photochemical inactivation of pathogens in blood product units described in this specification has been well established to provide such blood products (e.g., platelet compositions) suitable for transfusion into humans. In some embodiments, suitability refers to meeting one or more standards established by an authority or regulatory body governing transfusion practices, such as the AABB (e.g., having a certain level of biological activity or biological content, safety standards, etc.). In some embodiments, suitability of a platelet composition subjected to pathogen inactivation (e.g., photochemical pathogen inactivation using amitosalin / UVA light) refers to a platelet composition having a PIC concentration (e.g., residual PIC) below a certain level after the pathogen inactivation process.

[0046] As used herein, the terms "under sterile conditions" or "in a sterile manner" refer to maintaining the sterility of a system, such as by connecting two bags by a blood processing kit; or to a manner by which the process does not introduce contamination. For example, as used in the methods described herein, a source unit of a blood product, such as a platelet preparation (e.g., in a suitable container) can be joined under sterile conditions by methods known in the art, such as using a sterile connection device that acts to melt or weld the tubes together to provide a sterile flow path between the two containers. Similarly, when the methods described herein describe sealing such tubes, the sealing is performed under sterile conditions, such as using a tubing weld.

[0047] Method for preparing platelet composition

[0048] In some aspects, the present disclosure provides a method for preparing a platelet composition (e.g., a pathogen-inactivated platelet composition), comprising: (a) providing (e.g., in a first container) a solution comprising a platelet additive solution (PAS) and a pathogen-inactivating compound (PIC); (b) mixing the solution of step (a) with a platelet preparation; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition.

[0049] The method for preparing a platelet composition disclosed in this specification (e.g., a pathogen-inactivated platelet composition) includes: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen-inactivating compound (PIC), wherein the solution comprising PAS and PIC has a sufficient volume for preparing any number of platelet compositions (e.g., platelet units or therapeutic doses). In some embodiments, the first container of step (a) contains a sufficient volume of a solution comprising (PAS) and a pathogen-inactivating compound (PIC) for preparing one platelet composition (e.g., platelet unit, therapeutic dose). In some embodiments, the first container of step (a) contains a sufficient volume of a solution comprising (PAS) and a pathogen-inactivating compound (PIC) for preparing two or more (e.g., three) platelet compositions. In some embodiments, the first container of step (a) contains a sufficient volume of a solution comprising (PAS) and a pathogen-inactivating compound (PIC) for preparing a platelet composition from one platelet donor. In some embodiments, the first container of step (a) comprises a sufficient volume of a solution comprising (PAS) and a pathogen inactivating compound (PIC) for preparing a platelet composition from two or more platelet donors.

[0050] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the solution of step (a) with a platelet preparation in the first container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to light in the first container. In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to light in step (c). In some embodiments, the first container comprises a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing the platelet composition.

[0051] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the solution of step (a) with a platelet preparation in a second container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to light in the second container. In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the light of step (c). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing the platelet composition.

[0052] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the solution of step (a) with a platelet preparation in the first container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to a fluid flow path or channel of the apheresis device. In some embodiments, the first container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the first container. In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first container comprises a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0053] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the solution of step (a) with a platelet preparation in a second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to a fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the light of step (d). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0054] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container and a second container to an apheresis device; (c) mixing the solution of step (a) with a platelet preparation in the second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first and / or second container is aseptically connected to the apheresis device. In some embodiments, the first and / or second container is connected to a fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0055] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the mixture of step (a) with a platelet preparation in the first container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to light in the first container. In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to light in step (c). In some embodiments, the first container comprises a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing the platelet composition.

[0056] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the mixture of step (a) with a platelet preparation in a second container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to light in the second container. In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the light of step (c). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing the platelet composition. In some embodiments, the method further comprises the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing the platelet composition.

[0057] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the mixture of step (a) with a platelet preparation in the first container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to a fluid flow path or channel of the apheresis device. In some embodiments, the first container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the first container. In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation in the mixing of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first container comprises a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0058] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the mixture of step (a) with a platelet preparation in a second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to a fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation in the mixing of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0059] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container and a second container to an apheresis device; (c) mixing the mixture of step (a) with a platelet preparation in the second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition. In some embodiments, the first and / or second container is aseptically connected to the apheresis device. In some embodiments, the first and / or second container is connected to a fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation in the mixing of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to a container comprising CAD. In some embodiments, the container comprising CAD is suitable for storing platelet compositions. In some embodiments, the method further comprises the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0060] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the solution of step (a) with a platelet preparation in the first container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (c). In some embodiments, the first container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to illumination in the first container. In some embodiments, the first container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0061] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the solution of step (a) with a platelet preparation in a second container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (c). In some embodiments, the second container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to light in the second container. In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0062] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the solution of step (a) with a platelet preparation in the first container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to the fluid flow path or channel of the apheresis device. In some embodiments, the first container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to illumination in the first container. In some embodiments, the first container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0063] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the solution of step (a) with a platelet preparation in a second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to the fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a substantially translucent material within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0064] In some embodiments, a method is provided, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container and a second container to an apheresis device; (c) mixing the solution of step (a) with a platelet preparation in a second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution comprising PAS and PIC is combined with the platelet preparation during the mixing process of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first and / or second container is aseptically connected to the apheresis device. In some embodiments, the first and / or second container is connected to the fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a substantially translucent material within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0065] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the mixture of step (a) with a platelet preparation in the first container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution of PAS and PIC combined in step (a) is combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (c). In some embodiments, the first container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to illumination in the first container. In some embodiments, the first container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0066] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the mixture of step (a) with a platelet preparation in a second container; and (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (c) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution of PAS and PIC combined in step (a) is combined with the platelet preparation during the mixing process of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (c). In some embodiments, the second container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (b) is subjected to light in the second container. In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (c), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0067] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the mixture of step (a) with a platelet preparation in the first container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation in the mixing of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to the fluid flow path or channel of the apheresis device. In some embodiments, the first container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to illumination in the first container. In some embodiments, the first container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0068] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container to an apheresis device; (c) mixing the mixture of step (a) with a platelet preparation in a second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation in the mixing of step (b), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first container is aseptically connected to the apheresis device. In some embodiments, the first container is connected to the fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0069] In some embodiments, a method is provided, comprising: (a) combining (e.g., mixing) a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) connecting the first container and the second container to an apheresis device; (c) mixing the mixture of step (a) with a platelet preparation in the second container; and (d) subjecting the mixture of step (c) to light sufficient to photochemically inactivate pathogens (if present), thereby producing a platelet composition, wherein the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) is suitable for transfusion into a subject without further processing, including without exposure to a compound adsorption device (CAD) to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens (e.g., at least 4 logs of pathogens), and wherein the platelet composition after step (d) comprises less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution of PAS and the solution of PIC combined in step (a) are combined with the platelet preparation in the mixing of step (c), and incubated for a period of 30 minutes to 24 hours, and then the mixture is subjected to the illumination of step (d). In some embodiments, the first and / or second container is aseptically connected to the apheresis device. In some embodiments, the first and / or second container is connected to the fluid flow path or channel of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum), and the mixture of step (c) is subjected to light in the second container. In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the method further includes the following step (d), transferring (e.g., in a sterile manner) the platelet composition to at least one (e.g., 1, 2 or 3) container suitable for storing platelet compositions.

[0070] In any or all of the foregoing embodiments, providing a solution comprising PAS and PIC in a first container comprises first merging a PAS solution and a solution of PIC to produce a solution comprising PAS and PIC. In any or all of the foregoing embodiments, the method comprises merging a PAS solution and a PIC solution to produce a solution comprising PAS and PIC before step (a). In some embodiments, the solution of PAS comes from a PAS container (e.g., a PAS storage container). In some embodiments, the solution of PIC comes from a PIC container (e.g., a PIC storage container). In some embodiments, the solution of PAS and the solution of PIC are merged in the first container of step (a). In some embodiments, the first container of step (a) is a PAS container. In some embodiments, the solution of PAS and the solution of PIC are merged less than 24 hours (e.g., within 24 hours) before the mixing of step (b). In some embodiments, the first container of step (a) is a PIC container. In some embodiments, the PAS container is connected to a single blood collection device. In some embodiments, the PIC container is connected to a single blood collection device.

[0071] In any or all of the foregoing embodiments, the container containing the mixture of platelet additive solution (PAS), pathogen inactivating compound (PIC), and platelet preparation can be disconnected from the apheresis device (e.g., in a sterile manner) and the mixture can be subjected to light sufficient to photochemically inactivate pathogens (if present).

[0072] In some aspects, the present disclosure provides a method for preparing a platelet composition from a platelet preparation, which is suitable for transfusion into an individual. In some embodiments of any of the methods, kits, and compositions described in this specification, one or more preparations of platelets are treated with the methods described in this specification, thereby obtaining one or more platelet compositions. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens, and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing to remove residual PIC or its photochemical product. In some embodiments, the method is sufficient to inactivate at least 1 log of pathogens, and wherein the platelet composition after step (c) contains 5 μM or less of PIC. In some embodiments, the concentration of PIC in the mixture of step (b) is at least 10 μM.

[0073] Platelet preparations

[0074] In some embodiments, platelet preparations are prepared from one or more, for example, at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 platelet donations obtained by apheresis. In some embodiments, platelet preparations are prepared from one or more, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 platelet donations obtained by apheresis. In some embodiments, platelet preparations are prepared from one or more, for example, at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 whole blood-derived (e.g., PRP, buffy coat) platelet donations. In some embodiments, the platelet preparation is prepared from one or more, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 whole blood-derived (e.g., PRP, buffy coat) platelet donations.

[0075] Platelets collected by apheresis

[0076] In some embodiments of any of the methods, kits, and compositions described herein, the platelet preparation is prepared by an apheresis procedure.

[0077] Apheresis generally refers to a method using an automated blood collection device (e.g., an apheresis device) that automatically extracts whole blood from a donor using centrifugation or filtration separation, separates the whole blood into blood components, collects certain components (e.g., platelets), and returns some or all of the remainder of the whole blood and / or the remaining uncollected blood components to the donor. Platelet removal is platelets collected using such an automated blood cell separator device that can obtain a high yield of platelets (e.g., apheresis platelets) from a single donor. In some embodiments, the collected platelets are used to maintain a desired amount of plasma. Some apheresis devices can be used not only for methods of collecting single platelet units, but also for methods of collecting double and triple platelet units. Apheresis devices can also include a container for an anticoagulant, from which the anticoagulant is metered into the flow path and mixed with the incoming whole blood. Anticoagulants are required because blood tends to clot and adhere to the plastic surface walls in contact with it. Exemplary anticoagulants are well known in the art and can include, but are not limited to, anticoagulant citrate-phosphate-dextrose (CPD) solution, anticoagulant citrate phosphate diglucose (CP2D) solution, anticoagulant citrate-phosphate-dextrose-adenine (CPDA) solution (e.g., CPDA-1), acid citrate dextrose (ACD) solution (e.g., ACD-A), and anticoagulant sodium citrate 4% w / v solution. Apheresis collection devices are well known in the art, and there are several such devices commercially available, including, for example, Systems (Fenwal, Inc.), Trima System (Terumo BCT) and Mobile system (Haemonetics, Inc.).

[0078] Apheresis platelet donations are based on certain donor parameters, such as sex, body size (e.g., weight), hemoglobin levels, platelet counts on the day of donation, previous donation history, and donation frequency, in part to ensure that only a safe amount of platelets is collected. Any or all of these parameters can be input into a computer system and / or apheresis collection device. From these parameters, apheresis platelet donations are generally collected from individual donors to produce one, two, or three platelet units (e.g., therapeutic dose units), each unit containing a specified minimum number (e.g., at least a specified minimum number) of platelets to meet therapeutic dose requirements, typically per unit or therapeutic dose standards determined by government, regulatory, or authorized organizations (e.g., industry) standards. Non-limiting examples of such standards include, for example, those proposed by FDA, EDQM, AABB, PMDA, TGA, and SFDA. For example, the specified minimum value may vary from country to country. Typically, the platelet number can be determined for each unit of a platelet preparation, for example, based on a platelet count and information prior to donation (information about the volume collected) or by post-collection testing of the unit. In some embodiments, each unit of a platelet preparation contains a minimum platelet number; however, determining the platelet number for each unit may not be an absolute requirement, and some of the plurality of platelet units may be less than a specified number.

[0079] Whole blood collection and platelet processing

[0080] In some embodiments of any of the methods, kits, and compositions described herein, the platelet preparation is prepared from one or more whole blood donations by a buffy coat method or a platelet rich plasma (PRP) method.

[0081] In some embodiments, the platelet preparation is prepared from one or more whole blood donations by the buffy coat method.

[0082] In some embodiments, the platelet preparation is prepared from one or more whole blood donations by a platelet rich (PRP) method.

[0083] Whole blood for preparation as described above can be collected by a variety of methods known in the art. One of the most common blood collection techniques is to collect whole blood from a donor "manually". As generally understood and used in this specification, manual collection refers to a collection method in which whole blood is discharged from a donor and into a collection container without the use of an external pump or similar device. This is in contrast to so-called automatic methods in which blood is withdrawn from a donor and further processed by an instrument that typically includes a processing or separation device and a pump for moving blood or blood components into or out of the device.

[0084] Drawing blood from a donor typically involves inserting a venous access device (e.g., a needle) into the donor's arm (more specifically, the donor's vein) and drawing blood from the donor through the needle. The "venipuncture" needle is typically connected to one end of a plastic tube that provides a flow path for the blood. The other end of the plastic tube terminates in one or more pre-connected plastic blood containers or bags for collecting blood. The needle, tube, and container constitute a blood collection kit that is pre-sterilized and discarded after a single use. Sterile blood collection containers are typically used as the primary container for the initial separation of blood components (e.g., separation of plasma from red blood cells and platelets).

[0085] The blood collection container and plastic tube may also include a volume of liquid anticoagulant, and in automated technology, a separate anticoagulant container may be provided from which the anticoagulant is metered into the flow path and mixed with the incoming whole blood. Anticoagulants are required because blood tends to coagulate and adhere to the walls of the plastic surface to which it is adhered. Exemplary anticoagulants are well known in the art and may include, but are not limited to, anticoagulant citrate-phosphate-dextrose (CPD) solutions, anticoagulant citrate phosphate diglucose (CP2D) solutions, anticoagulant citrate-phosphate-dextrose-adenine (CPDA) solutions (e.g., CPDA-1), acid citrate dextrose (ACD) solutions (e.g., ACD-A), and anticoagulant sodium citrate 4% w / v solutions.

[0086] One or more parameters such as hematocrit can be used to identify or characterize blood. This identification or characterization is typically performed before or after blood collection, but before further processing of the collected whole blood, for example, according to the provided method. In addition, tests can be performed to determine the blood type and the presence of pathogens in the donor blood, for example, the presence of viruses, bacteria and / or other foreign matter, at or near the time of collection and before transfusion of blood to the patient. Such tests usually require obtaining a blood sample from the donor. Typically, blood sampling can be performed before, during or after blood donation, but does not affect the sterility of the system and / or the blood products collected. For example, samples can usually be obtained by finger sticks, heel sticks or venipuncture. If blood for hemoglobin testing is collected with a capillary stick, a disposable sterile blood collection needle can be used. Another well-known technique is to simply draw or collect the blood remaining in the flow path of the collection device after donation. This involves removing the needle from the donor, inserting the needle into a vacuum-sealed sampling vial or test tube, and allowing the blood to drain from the flow path into the vial. Another option is to clamp the flow path near the collection container and transfer the blood drawn from the donor to a collection (sampling) vial or test tube. The method can use a special type of disposable tubing kit that has a pre-connected sampling site on the main flow path, and blood at or near the sampling site can be obtained by piercing the sampling site with a separately provided needle or other puncture device and connecting a sampling vial to it. In order to minimize the risk of exposure of the incoming blood to the external environment, the sample is typically collected after the blood donation is completed. Alternatively, some collection bags or collection kits include a transfer bag to isolate a portion (e.g., the initial 20 ml) of blood. Another example of a blood collection system is described in U.S. Patent No. 5,167,656 (incorporated herein in its entirety by reference), which describes a blood collection device having an enlarged sample collection portion included in the flow path, which is used to sample blood by cutting off the flow path near the collection container and allowing the enlarged tubing portion to be filled with blood.

[0087] The buffy coat method is well known in the art. The buffy coat method comprises separating the blood components of an uncoagulated blood sample by centrifugation to obtain a layer comprising plasma, a layer comprising red blood cells, and a layer comprising platelets and leukocytes (i.e., a buffy coat). After centrifugation, the buffy coat can be separated from other blood components to obtain a platelet preparation.

[0088] Platelet-rich plasma (PRP) methods are well known in the art. The PRP method comprises separating the blood components of an uncoagulated blood sample by centrifugation to obtain a layer comprising red blood cells and a layer comprising plasma and platelets. After centrifugation, the plasma and platelet layers can be separated from the other blood components (and optionally further centrifuged to concentrate the platelets) to obtain a platelet preparation.

[0089] Pathogen Inactivating Compounds (PIC)

[0090] In some embodiments of any of the methods, kits, and compositions provided herein, pathogen inactivation requires the addition of a certain amount of a pathogen inactivating compound (e.g., to a platelet preparation). For example, pathogen inactivation may involve the addition of low molecular weight compounds that inactivate various pathogens, wherein a particular method includes the addition of a photosensitizer that, when activated by illumination with light of a suitable wavelength, inactivates a variety of pathogens that may be present. Two commercially available methods include the addition of amitosalin or riboflavin to platelets followed by illumination with UV light. Other methods include irradiation with additional photoactive compounds, including psoralen derivatives other than amitosaline, isoalloxazines other than riboflavin, alloxazines, dyes such as phthalocyanines, phenothiazine dyes (e.g., methylene blue, azure B, azure C, thionine, toluidine blue), porphyrin derivatives (e.g., dihematoporphyrin ethers, hematoporphyrin derivatives, benzene-porphyrin derivatives, alkyl-substituted sapphyrins), and merocyanine 540 (Prodouz et al., Blood Cells 1992, 18(1): 101-14; Sofer, Gail, BioPharm, August 2002). In some embodiments, the pathogen inactivating compound is a photoactive pathogen inactivating compound. In some embodiments, the pathogen inactivating compound (PIC) is psoralen. In some embodiments, the pathogen inactivating compound (PIC) is amitosaline. In some embodiments, the pathogen inactivating compound (PIC) is selected from isoalloxazines, alloxazines, phthalocyanines, phenothiazines, porphyrins, merocyanine 540, and salts or free bases thereof.

[0091] Platelet Additive Solution (PAS)

[0092] Platelet additive solutions are known in the art, for example, as described by Alhumaidan et al. and Ringwald et al. (Alhumaidan, H. and Sweeney, J., J Clin Apheresis, 27: 93-98 (2012); Ringwald et al., Transfusion Medicine Reviews, 20: 158-64 (2006)), the entire contents of which are incorporated herein by reference. In some embodiments of any of the methods, kits, and compositions provided in this specification, the platelet additive solution (PAS) comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate. In some embodiments of any of the methods, kits, and compositions provided in this specification, the platelet additive solution (PAS) is a PAS approved by a regulatory agency or accredited organization recognized in the art.

[0093] In some embodiments of any of the methods, kits, and compositions provided herein, the platelet additive solution (PAS) comprises one or more of sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, sodium gluconate, glucose, and sodium bicarbonate.

[0094] In some embodiments, PAS comprises chloride, citrate, phosphate and potassium. In some embodiments, PAS comprises chloride, citrate and acetate. In some embodiments, PAS comprises chloride, citrate, phosphate and acetate. In some embodiments, PAS comprises chloride, citrate, acetate, magnesium, potassium and gluconate. In some embodiments, PAS comprises chloride, citrate, phosphate, magnesium and potassium. In some embodiments, PAS comprises chloride, acetate, magnesium, potassium and gluconate. In some embodiments, PAS comprises chloride, citrate, phosphate, acetate, magnesium, potassium and gluconate. In some embodiments, PAS comprises chloride, citrate, phosphate, acetate, magnesium, potassium and glucose.

[0095] In some embodiments, PAS comprises sodium chloride, sodium acetate, potassium chloride, magnesium chloride and sodium gluconate. In some embodiments, PAS comprises sodium chloride, sodium acetate and sodium citrate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate and sodium phosphate. In some embodiments, PAS comprises sodium chloride, sodium citrate, sodium phosphate and potassium chloride. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride and sodium phosphate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride and sodium phosphate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride and sodium gluconate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, glucose and sodium bicarbonate. In some embodiments, PAS comprises sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, glucose and sodium bicarbonate.

[0096] In some embodiments, PAS is PAS-I. In some embodiments, PAS is PlasmaLyte. In some embodiments, PAS is Pas-II. In some embodiments, PAS is T-Sol. In some embodiments, PAS is PAS-III. In some embodiments, PAS is Intersol. In some embodiments, PAS is PAS-IIIM SSP. In some embodiments, PAS is ComposolPAS-G. In some embodiments, PAS is M-Sol. In some embodiments, PAS is Isoplate. In some embodiments, PAS is PAS-A. In some embodiments, PAS is PAS-B. In some embodiments, PAS is PAS-C. In some embodiments, PAS is PAS-D. In some embodiments, PAS is PAS-E. In some embodiments, PAS is PAS-F. In some embodiments, PAS is PAS-G.

[0097] Solutions of PAS and PIC

[0098] Typically, the solution comprising PAS and PIC can have any volume sufficient for any method, kit and composition described in this specification. In some embodiments of any one of the methods, kits and compositions described in this specification, the solution comprising PAS and PIC has a volume of about 100 mL to about 1000 mL. In some embodiments, the solution comprising PAS and PIC has a volume of about 200 mL to about 900 mL, about 300 mL to about 800 mL, about 400 mL to about 700 mL or about 500 mL to about 600 mL. In some embodiments, the solution comprising PAS and PIC has a volume of about 100 mL, about 200 mL, about 300 mL, about 400 mL, about 500 mL, about 600 mL, about 700 mL, about 800 mL, about 900 mL or about 1000 mL. In some embodiments, the solution comprising PAS and PIC has a volume of less than about 1000 mL, less than about 800 mL, less than about 600 mL, less than about 500 mL, less than about 400 mL, less than about 300 mL, or less than about 200 mL. In some embodiments, the solution comprising PAS and PIC has a volume greater than about 800 mL, greater than about 700 mL, greater than about 600 mL, greater than about 500 mL, greater than about 400 mL, greater than about 300 mL, greater than about 200 mL, or greater than about 100 mL. In some embodiments, the solution comprising PAS and PIC has a volume of about 1000 mL to about 5000 mL.

[0099] Generally, the concentration of PIC in the solution comprising PAS and PIC can be any suitable PIC concentration that provides a "final" desired PIC concentration when the solution comprising PAS and PIC is mixed with a platelet preparation, which is used in any of the methods, kits and compositions described in this specification, such as when the solution comprising PAS and PIC is mixed with a platelet preparation, taking into account the combined volume. In some embodiments, the concentration of PIC in the solution comprising PAS and PIC is about 25 μM to about 1200 μM, about 50 μM to about 1000 μM, about 50 μM to about 750 μM, about 50 μM to about 500 μM, about 75 μM to about 500 μM, about 100 μM to about 400 μM, about 150 μM to about 350 μM, about 200 μM to about 300 μM, or about 225 μM to about 250 μM. In some embodiments, the concentration of PIC in the solution comprising PAS and PIC is about 25 μM, about 50 μM, about 75 μM, about 100 μM, about 125 μM, about 150 μM, about 175 μM, about 200 μM, about 250 μM about 275 μM, about 300 μM, about 325 μM, about 350 μM, about 375 μM, about 400 μM, about 450 μM, about 500 μM, about 550 μM, about 600 μM, about 650 μM, about 700 μM, about 750 μM, about 800 μM, about 850 μM, about 900 μM, about 1000 μM, about 1100 μM, about 1200 μM, about 1300 μM, about 1400 μM, or about 1500 μM. In some embodiments, the concentration of PIC in the solution comprising PAS and PIC is about 225 μM to about 235 μM. In some embodiments, the concentration of PIC in the solution comprising PAS and PIC is about 225 μM, about 226 μM, about 227 μM, about 228 μM, about 229 μM, about 230 μM, about 231 μM, about 232 μM, about 233 μM, about 234 μM, or about 235 μM.

[0100] In some embodiments, the solution comprising PAS and PIC comes from merging PAS solution and PIC solution to produce a solution comprising PAS and PIC. In some embodiments, the method includes merging PAS solution and PIC solution to produce a solution comprising PAS and PIC before step (a). In some embodiments, the solution of PAS comes from a PAS container (e.g., a PAS storage container). In some embodiments, the solution of PIC comes from a PIC container (e.g., a PIC storage container). In some embodiments, less than (e.g., within) about 6 months, less than about 4 months, less than about 3 months, less than about 2 months, less than about 1 month, less than about 3 weeks, less than about 2 weeks, less than about 1 week, less than about 5 days, less than about 4 days, less than about 3 days, less than about 48 hours, less than about 36 hours, less than about 24 hours, less than about 18 hours, less than about 12 hours, less than about 8 hours, less than about 6 hours, less than about 4 hours, less than about 2 hours or less than about 1 hour before the solution comprising PAS and PIC is mixed with the platelet preparation. In some embodiments, the solution of PAS and the solution of PIC are combined about 5 minutes to about 72 hours, about 5 minutes to about 48 hours, about 5 minutes to about 36 hours, about 5 minutes to about 24 hours, about 5 minutes to about 18 hours, about 5 minutes to about 12 hours, about 5 minutes to about 8 hours, about 5 minutes to about 6 hours, about 5 minutes to about 4 hours, about 5 minutes to about 2 hours, or about 5 minutes to about 1 hour before mixing the solution comprising PAS and PIC with the platelet preparation.

[0101] Mixture of PAS, PIC and platelet preparation

[0102] In some embodiments of any of the methods, kits and compositions described in this specification, the volume of the mixture of PAS, PIC and platelet preparation is about 100 mL to about 1000 mL. In some embodiments, the volume of the mixture of PAS, PIC and platelet preparation is about 200 mL to about 800 mL, about 200 mL to about 775 mL, about 250 mL to about 775 mL, about 225 mL to about 525 mL, about 500 mL to about 775 mL, about 200 mL to about 300 mL, about 300 mL to about 400 mL, about 400 mL to about 500 mL, about 500 mL to about 600 mL, about 600 mL to about 700 mL or about 700 mL to about 800 mL. In some embodiments, the volume of the mixture of PAS, PIC and platelet preparation is about 255 mL, 510 mL or about 765 mL. In some embodiments, the mixture of PAS, PIC, and platelet preparation has a ratio of PAS to plasma of about 65:35, wherein the platelet preparation comprises plasma.

[0103] In some embodiments, the total volume of the mixture of PAS, PIC and platelet preparation (wherein the platelet preparation comprises plasma) contains about 32% to about 47% volume plasma. In some embodiments, the total volume of the mixture of PAS, PIC and platelet preparation comprises about 53% to about 63% volume PAS, wherein the platelet preparation comprises plasma. In some embodiments, plasma comprises a mixture of about 32-47% volume of PAS, PIC and platelet preparation, wherein the platelet additive solution (e.g., a platelet additive solution with PIC) comprises the remaining volume (i.e., 53-68% PAS, wherein % plasma + % PAS = 100). The plasma volume can also include, for example, any volume of non-PAS (e.g., PIC PAS with), for example, any volume associated with platelets and / or any volume associated with the anticoagulant used during the treatment process. In some embodiments, the platelet preparation comprises about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, or about 47% plasma by volume of the mixture of PAS, PIC, and platelet preparation. In some embodiments, the volume ratio of PAS to plasma in the mixture of PAS, PIC, and platelet preparation is about 68:32, about 67:33, about 66:34, about 65:35, about 64:36, about 63:37, about 62:38, about 61:39, about 60:40, about 59:41, about 58:42, about 57:43, about 56:44, about 55:45, about 54:46, or about 53:47.

[0104] Pathogen inactivation

[0105] In some embodiments of any of the methods, kits, and compositions described herein, the mixture of PAS, PIC, and platelet preparation comprises a concentration of PIC sufficient to result in at least about 1 log inactivation of a pathogen (if present). In some embodiments, the mixture of PAS, PIC, and platelet preparation comprises a concentration of PIC sufficient to result in at least about 1 log inactivation of a pathogen (if present) after the mixture is exposed to light sufficient to photochemically inactivate the pathogen. In some embodiments, the concentration of PIC is sufficient to result in at least about 1 log, at least about 2 logs, at least about 3 logs, at least about 4 logs, at least about 5 logs, at least about 6 logs, or at least about 7 logs, at least about 8 logs, at least about 9 logs, or at least about 10 log inactivation of a pathogen (if present) (e.g., after the mixture is exposed to light sufficient to photochemically inactivate the pathogen).

[0106] In some embodiments of any of the methods, kits, and compositions described herein, the mixture of PAS, PIC, and platelet preparation comprises PIC at a concentration of about 5 μM to about 500 μM. In some embodiments, the mixture comprises PIC at a concentration of less than about 150 μM. In some embodiments, the mixture comprises a concentration of about 15 μM to about 400 μM, about 25 μM to about 300 μM, about 50 μM to about 250 μM, about 75 μM to about 225 μM, about 100 μM to about 200 μM, about 125 μM to about 175 μM, about 25 μM to about 250 μM, about 25 μM to about 200 μM, about 25 μM to about 150 μM, about 25 μM to about 100 μM, about 25 μM to about 50 μM, about 25 μM to about 35 μM, about 30 μM to about 150 μM, about 30 μM to about 90 μM, about 50 μM to about 150 μM, about 50 μM to about 100 μM. In some embodiments, the mixture comprises a PIC at a concentration of about 145 μM to about 155 μM. In some embodiments, the mixture comprises PIC at a concentration of about 145 μM, about 146 μM, about 147 μM, about 148 μM, about 149 μM, about 150 μM, about 151 μM, about 152 μM, about 153 μM, about 154 μM, or about 155 μM. In some embodiments, the mixture comprises PIC at a concentration of about 10 μM, about 15 μM, about 20 μM, about 25 μM, about 30 μM, about 35 μM, about 40 μM, about 45 μM, about 50 μM, about 55 μM, about 60 μM, about 65 μM, about 70 μM, about 75 μM, about 80 μM, about 85 μM, about 90 μM, about 95 μM, about 100 μM, about 110 μM, about 120 μM, about 130 μM, or about 140 μM.

[0107] In some embodiments of any of the methods, kits, and compositions provided herein, a mixture of PAS, PIC, and a platelet preparation comprising about 2.0 x 10 11 Platelets to about 14.0x10 11In some embodiments, the mixture comprises at least about 2.0 x 10 11 platelets, at least about 3.0x10 11 platelets, at least about 4.0x10 11 platelets, at least about 5.0x10 11 platelets, at least about 6.0x10 11 platelets, at least about 7.0x10 11 Platelets, at least about 8.0x10 11 platelets, at least about 9.0x10 11 platelets, at least about 10.0x10 11 platelets, at least about 11.0x10 11 Platelets or at least about 12.0x10 11 Platelets. In some embodiments, the platelet preparation comprises at least about 2.0 x 10 11 platelets, at least about 2.2x10 11 platelets, at least about 2.4x10 11 platelets, at least about 2.5x10 11 platelets, at least about 2.6x10 11 platelets, at least about 2.7x10 11 platelets, at least about 2.8x10 11 platelets, at least about 2.9x10 11 platelets or at least about 3.0x10 11 Platelets.

[0108] In some embodiments, the method for preparing a platelet composition further comprises incubating the mixture of PAS, PIC and platelet preparation for a period of about 30 minutes to about 24 hours, wherein the incubation is performed before subjecting the mixture to illumination sufficient to photochemically inactivate pathogens (if present). Incubating before subjecting the mixture to illumination sufficient to photochemically slow illumination can be referred to as pre-incubation. In some embodiments, the mixture of PAS, PIC and platelet preparation is incubated for less than about 24 hours, less than about 22 hours, less than about 20 hours, less than about 18 hours, less than about 16 hours, less than about 14 hours, less than about 12 hours, less than about 10 hours, less than about 8 hours, less than about 6 hours, less than about 5 hours, less than about 4 hours, less than about 3 hours, less than about 2 hours or less than about 1 hour before subjecting the mixture to illumination sufficient to photochemically inactivate pathogens (if present). In some embodiments, the mixture of PAS, PIC, and platelet preparation is incubated for a period of greater than about 22 hours, greater than about 20 hours, greater than about 18 hours, greater than about 16 hours, greater than about 14 hours, greater than about 12 hours, greater than about 10 hours, greater than about 8 hours, greater than about 6 hours, greater than about 5 hours, greater than about 4 hours, greater than about 3 hours, greater than about 2 hours, greater than about 1 hour, or greater than about 30 minutes before subjecting the mixture to light sufficient to photochemically inactivate pathogens, if present. In some embodiments, the mixture of PAS, PIC, and platelet preparation is incubated for about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 12 hours, about 14 hours, about 16 hours, about 18 hours, about 20 hours, about 22 hours, or about 24 hours before subjecting the mixture to light sufficient to photochemically inactivate pathogens, if present. Incubating a mixture of PAS, PIC, and platelet preparations for a period of about 30 minutes to about 24 hours prior to subjecting the mixture to illumination sufficient to photochemically inactivate pathogens can result in improved pathogen inactivation. In some embodiments, such pre-incubation can result in an increase in the degree of inactivation of pathogens present in the platelet preparations compared to the degree of inactivation of pathogens (i.e., the same pathogens) by the same platelet composition preparation method but without a pre-incubation step. The increase in the degree of pathogen inactivation can be at least 1 log, at least 2 logs, at least 3 logs, at least 4 logs, at least 5 logs, at least 6 logs, at least 7 logs, at least 8 logs, at least 9 logs, or at least 10 logs of pathogen inactivation. In some embodiments, preincubation can result in an increase (e.g., an increase of at least 1, 2, 3, 4, or 5 logs) in the number of pathogens that can be inactivated (if present in the platelet preparation) compared to the number of pathogens that can be inactivated (if present in the platelet preparation) as a result of the same method for preparing the platelet composition but without the preincubation step.In some embodiments, the improvement in pathogen inactivation described herein is demonstrated with respect to one or more bacteria or viruses (eg, enveloped viruses, non-enveloped viruses), or parasites.

[0109] In some embodiments of any of the methods, kits, and compositions described herein, the wavelength of light to which the mixture of PAS, PIC, and platelet preparation is subjected is about 200 nm to about 400 nm. In some embodiments, the wavelength of light is within the ultraviolet A spectrum (e.g., about 315-400 nm). In some embodiments, the duration of light is about 1 second to about 30 minutes. In some embodiments, the intensity of light is about 1 to about 30 mW / cm 2 In some embodiments, the dose of light is about 1 J / cm 2 About 20J / cm 2 .

[0110] In some embodiments of any of the methods described herein, the method is sufficient to inactivate at least 1 log of pathogens, and the platelet composition after the mixture of the platelet preparation and the solution comprising PAS and PIC (e.g., the mixture of step (b) is subjected to light) is suitable for transfusion into a subject without further processing to remove residual PIC or its photochemical product. In some embodiments, the method is sufficient to inactivate at least 2 logs, at least 3 logs, or at least 4 logs or more of pathogens, and the platelet composition after the mixture of the platelet preparation and the solution comprising PAS and PIC (e.g., the mixture of step (b)) is subjected to light is suitable for transfusion into a subject without further processing to remove residual PIC or its photochemical product. In some embodiments, the platelet composition suitable for transfusion into a subject comprises about 5 μM or less, about 4 μM or less, about 3 μM or less, about 2 μM or less, about 1 μM or less, or about 0.5 μM or less of PIC. In some embodiments, a platelet composition suitable for transfusion into a subject comprises less than about 5 μM, less than about 4 μM, less than about 3 μM, less than about 2 μM, less than about 1 μM, or less than about 0.5 μM or less PIC. In some embodiments of any of the methods described herein, the method is sufficient to inactivate at least 1 log of pathogens, and the platelet composition after step (c) (e.g., after subjecting the mixture of the platelet preparation and the solution comprising PAS and PIC to light) comprises about 5 μM or less PIC. In some embodiments, the method is sufficient to inactivate at least 2 logs, at least 3 logs, or at least 4 logs or less of pathogens, and the platelet composition after step (c) (e.g., after subjecting the mixture of the platelet preparation and the solution comprising PAS and PIC to light) comprises about 4 μM or less, about 3 μM or less, about 2 μM or less, about 1 μM or less, or about 0.5 μM or less PIC. In some embodiments, the platelet composition after step (c) (e.g., after subjecting the mixture of the platelet preparation and the solution comprising PAS and PIC to light) comprises less than 5 μM, less than 4 μM, less than 3 μM, less than 2 μM, less than 1 μM, or less than 0.5 μM PIC. For example, in some embodiments, the method is sufficient to inactivate at least 4 logs of pathogens, and the platelet composition after step (c) (e.g., after subjecting the mixture of the platelet preparation and the solution comprising PAS and PIC to light) comprises about 4 μM or less, about 3 μM or less, about 2 μM or less, about 1 μM or less, or about 0.5 μM or less (e.g., less than 5 μM, less than 4 μM, less than 3 μM, less than 2 μM, less than 1 μM, less than 0.5 μM) PIC.In some embodiments, the concentration of PIC in the mixture of step (b) is at least 10 μM, at least 15 μM, at least 20 μM, at least 25 μM, at least 30 μM, at least 40 μM, at least 50 μM, at least 60 μM, at least 70 μM, at least 80 μM, at least 90 μM, at least 100 μM, at least 110 μM, at least 120 μM, at least 130 μM, at least 140 μM, or at least 150 μM.

[0111] In some embodiments, a method of preparing a platelet composition comprises incubating a mixture of a platelet preparation and a solution comprising PAS and PIC for a period of about 30 minutes to about 24 hours and then subjecting the mixture to light, wherein: (a) the method is sufficient to inactivate at least 1 log, at least 2 logs, at least 3 logs, at least 4 logs, or at least 5 logs or more of the pathogen, if present; (b) the concentration of PIC in the mixture of PAS, PIC, and the platelet preparation is about 15 μM to about 150 μM and (c) the platelet composition after subjecting the mixture of the platelet preparation and the solution comprising PAS and PIC to light comprises less than 5 μM, less than 4 μM, less than 3 μM, less than 2 μM, less than 1 μM, or less than 0.5 μM PIC.

[0112] Platelet quality

[0113] The present disclosure also provides a platelet composition with improved platelet quality, which is suitable for transfusion (e.g., infusion into a human subject after pathogen inactivation), wherein the platelet composition is prepared by any method disclosed in this specification. For example, during storage after pathogen inactivation (e.g., as described in this specification), the platelet composition prepared by any method disclosed in this specification maintains favorable properties (particularly, suitable pH, but also including and not limited to dissolved oxygen, carbon dioxide, glucose, lactate, ATP, LDH, p-selectin expression (e.g., CD62P), cell morphology (e.g., morphological score), shape change or degree of ESC and hypovolemic shock reaction or HSR) for a longer time period and / or closer to the level of untreated (e.g., non-pathogen inactivation) platelet composition than using existing methods and processing kits. Such platelet composition features can be those known in the art and are typically measured, for example, using assays known in the art.

[0114] In some embodiments, the platelet composition prepared by any method disclosed in this specification maintains a pH even after pathogen inactivation and storage (e.g., for up to 7 days) that is closer to the pH of an untreated (e.g., non-pathogen inactivated) platelet composition or a platelet composition that has not been stored after pathogen inactivation. In some embodiments, the pH of the platelet composition prepared by any method disclosed in this specification is > 6.2, wherein the platelet composition is stored at room temperature for at least about 1 day after platelet inactivation, such as at least about any one of 2 days, 3 days, 4 days, 5 days, 6 days, and 7 days. In some embodiments, the pH of the platelet composition prepared by any method disclosed in this specification is > 6.4, wherein the platelet composition is stored at room temperature for at least about 1 day after platelet inactivation, such as at least about any one of 2 days, 3 days, 4 days, 5 days, 6 days, and 7 days.

[0115] Platelet Units

[0116] The disclosed invention also provides platelet compositions suitable for transfusion (eg, into a human subject), for example, platelet compositions prepared by any of the methods disclosed herein that contain a minimal number of platelets.

[0117] In some embodiments of any of the methods, kits, and compositions provided herein, the platelet composition comprises at least about 2.0 x 10 11 platelets, at least about 3.0x10 11 platelets, at least about 4.0x10 11 platelets, at least about 5.0x10 11 platelets, at least about 6.0x10 11 platelets, at least about 7.0x10 11 Platelets, at least about 8.0x10 11 platelets, at least about 9.0x10 11 platelets, at least about 10.0x10 11 platelets, at least about 11.0x10 11 platelets or at least about 12.0x10 11 In some embodiments, the platelet composition comprises at least about 2.0 x 10 11 platelets, at least about 2.2x10 11 platelets, at least about 2.4x10 11 platelets, at least about 2.5x10 11 platelets, at least about 2.6x10 11 platelets, at least about 2.7x10 11platelets, at least about 2.8x10 11 platelets, at least about 2.9x10 11 platelets or at least about 3.0x10 11 Platelets.

[0118] In some embodiments, the platelet composition comprises a therapeutic dose (e.g., a therapeutic dose unit) of platelets suitable for transfusion into a human subject (e.g., a subject in need of a platelet transfusion). In some embodiments, the therapeutic dose comprises a minimum number (e.g., at least a minimum number) of platelets defined by a standard (e.g., acceptance criteria) of a governmental agency, regulatory agency, agency, and / or authorized organization (e.g., a governmental agency, regulatory agency, agency, and / or authorized organization regarding donated blood products (e.g., donated platelets). In some embodiments, the regulatory agency is the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Australian Therapeutic Goods Administration (TGA), the China Food and Drug Administration (CFDA), or the Japan Ministry of Health, Labou and Welfare (MHLW). In some embodiments, the authorized organization is AABB or the European Directorate for the Quality of Medicines & HealthCare (EDQM). In some embodiments, the platelet composition is prepared in a country where a governmental agency, regulatory agency, agency and / or authorized organization defines standards for therapeutic doses of platelets. In some embodiments, the therapeutic dose unit of platelets contains at least about 2.0 x 10 11 platelets, at least about 2.2x10 11 platelets, at least about 2.4x10 11 , at least about 2.5x10 11 platelets, at least about 2.6x10 11 platelets, at least about 2.7x10 11 platelets, at least about 2.8x10 11 platelets, at least about 2.9x10 11 platelets or at least about 3.0x1011 Platelets. In some embodiments, a therapeutic dose unit of platelets comprises at least about 2.4 x 10 11 Platelets. In some embodiments, a therapeutic dose unit of platelets comprises at least about 2.6 x 10 11 In some embodiments, a therapeutic dose unit of platelets contains at least about 3.0 x 10 11 Platelets.

[0119] In some embodiments, the platelet composition includes platelets from multiple platelet compositions or platelet preparations. In some embodiments, the platelet composition includes platelets obtained from apheresis collected from two or more donors, and the platelets obtained from apheresis collected by any method disclosed in this specification sheet have been processed. In some embodiments, the platelet composition includes platelets (e.g., buffy coat platelets, PRP platelets) from whole blood sources collected from two or more donors, and the platelets collected by any method disclosed in this specification sheet have been processed. In some embodiments, multiple platelet compositions or platelet preparations are processed by the method disclosed in this specification sheet before collection. In some embodiments, multiple platelet compositions or platelet preparations are processed by the method disclosed in this specification sheet after collection. In some embodiments, the platelet composition includes platelets from donors of the same ABO blood type. In some embodiments, the platelet composition includes platelets from the same ABO and Rh type.

[0120] store

[0121] In some embodiments of any of the methods, kits, and compositions described herein, the platelet composition can be stored for at least 1 day, at least 2 days, at least 3 days, at least 3 days, at least 5 days, at least 6 days, or at least 7 days, for example, on a plate stirrer (e.g., 60 cycles 1 minute, model LPR-3, Melco, Glendale, CA, USA), in a temperature-controlled cabinet, for example, at 22±2°C. In some embodiments, the platelet composition can be stored for up to 5 days, up to 6 days, or up to 7 days, for example, on a plate stirrer (e.g., 6060 cycles 1 minute, model LPR-3, Melco, Glendale, CA, USA), in a temperature-controlled cabinet, for example, at 22±2°C.

[0122] Platelet processing

[0123] The platelet processing described in the present disclosure may involve the use of a blood product container or blood product bag system, which is well known in the art. Typically, such a system may include more than one plastic container, typically a plastic bag, wherein these bags may be integrally connected to a plastic tube. Some containers described in this specification include such plastic bags, as known in the storage and processing of blood products (including platelet products). Blood bags can typically be designed to accommodate different volumes of fluid, including but not limited to volumes from 50 mL to 2 liters, for example, with a capacity of up to 350 mL, a capacity of 450 mL, a capacity of 500 mL, a capacity of 1 liter, a maximum capacity of 1.5 liters or a maximum capacity of 2 liters. It should be understood that when a method involves a bag, it includes any such plastic bag for blood product processing. In the case of referring to such bags as "liquid collection bags", "mixing bags", "removal bags", "product bags", "storage bags" or "illumination bags", it should be understood that these bags are typical blood product processing bags or substantially similar to such bags. Plastic bags suitable for use according to the disclosed invention include, for example, plastic bags comprising PL2410, as well as other suitable plastic bags known in the art. Plastic bag materials include polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate blended with other plastics, and the like.

[0124] As described in this specification, where a tube is described as connecting, for example, two bags, such as two bags for a collection and / or processing kit, it should be understood that the tube can be joined at some point between them by another connecting component between the two bags. For example, a removal bag connected to a product bag by a tube includes a filter in which the tube contains the two bags, i.e., the tube is separated by the filter, allowing fluid to flow from one bag to another bag through the tube and the filter. In one example, the tube connecting the removal bag and the product bag can include a filter to remove any loose particles in the fluid flowing from the removal device to the product bag, i.e., the tube is separated or cut off by the filter between the bags. Such filters are designed to remove any small particles that may fall off the removal device while allowing platelets to pass through the filter. The tube between the bags allows fluid to flow from one bag to another bag, which can be cut off to stop the fluid until necessary, for example, as part of the process, the fluid in one bag can be prevented from flowing to the next bag until the bag is needed in the process. Therefore, in or on the pipe connecting the bag, include an openable seal, such as clamp, plug, valve, etc., wherein the clamp, plug, valve, etc. can be selectively opened as needed, for example, so that the conveying fluid is from one bag to the next bag. In certain embodiments, the pipe between the bags includes a fragile seal, such as a fragile valve, at this time, destroying the fragile seal makes the blood product solution flow through the pipe between the bags. It should be understood that the fragile seal is included in the connection between the containers, thereby maintaining the sterility of the system. It should also be understood that the pipe including a filter or a fragile seal is included in the situation where the pipeline may be interrupted by a filter or seal. For example, pipe extends from a bag and is connected to a filter or seal (the entry portion of pipe), and pipe continues to another bag (the outflow portion of pipe) from another part of the filter or seal. In such a structure, fluid is from a first bag, through the entry portion of pipe, through a filter or seal and through the outflow portion of pipe and flows into another bag.

[0125] Different containers (e.g., bags) in a blood product processing system can be used for different steps of the process. For example, a bag system for inactivating pathogens of platelet preparations may include one or more of the following: a container containing a pathogen inactivating compound (PIC), a container containing a platelet additive solution (PAS), a container containing PIC and PAS, a container for receiving a platelet preparation (e.g., a platelet donation) and a container for PIC and PAS (e.g., an irradiation bag), a bag for removing pathogen inactivating compounds and / or their byproducts from a platelet processing unit (e.g., referred to as a removal bag, a compound adsorption device, CAD), and one or more bags for containing a final platelet composition, such as a pathogen inactivated platelet unit (e.g., a therapeutic dose unit), which has a concentration of inactivating compounds and / or their byproducts reduced to less than a desired concentration, which can be used immediately or can be stored for later use (e.g., referred to as a product bag, a storage bag). Each bag in the system is typically made of plastic. For example, a container for containing a solution of a pathogen-inactivating compound can be made of a suitable plastic such as PL2411 (Baxter Healthcare) or other plastics, such as polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate, etc. blended with other plastics. The container is also packaged with a material that is opaque to a certain wavelength of light (e.g., a suitable plastic, such as PL2420, Baxter Healthcare), which will activate the photoactive pathogen-inactivating compound. The illumination bag for the photoactivated pathogen-inactivating compound requires a transparent, durable thermoplastic material that is semi-transparent to the selected wavelength of light. Suitable plastics that are semi-transparent in the UVA wavelength range include polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate blended with other plastics or other blends of thermoplastic polymers. Such suitable plastics include PL2410 (Baxter Healthcare) and PL732 (Baxter Healthcare). Similar materials can be used to make removal bags and product bags. Product bags include, for example, those made of PL2410. Suitable bag materials are discussed, for example, in PCT Publication No. WO 2003078023 and U.S. Pat. No. 7025877, which are incorporated herein by reference in their disclosures as they relate to such bag materials and related materials. In all cases, the materials used to prepare the processing kit must be sterilized by known methods, such as steam and gamma or electron beam radiation to ensure sterility of the processing kit. Although these are exemplary materials for making bags, the methods, kits, and compositions described can be adapted for use in processes using any suitable bag material, which is readily available to those skilled in the art, and can also be used with containers other than bags.Bags used for illumination, scavenging, and storage are also designed to allow gases such as oxygen and carbon dioxide to enter and leave the blood bag so that the platelets therein have an adequate oxygen supply and carbon dioxide level during processing and storage.

[0126] Certain aspects of the disclosed invention relate to processing kits. The processing kits of the disclosed invention can be particularly applied to prepare a variety of platelet compositions (e.g., platelet units) suitable for transfusion, for example, as described in this specification. Any of the exemplary components such as the bags and tubes described above can be applied to the processing kits of the disclosed invention.

[0127] Pathogen inactivation

[0128] Blood products, including blood products containing platelets, may contain pathogens, or may be contaminated by pathogens during processing. Therefore, it is desirable to subject such blood products to a pathogen inactivation process to reduce the risk of transfusion-transmitted diseases. Different methods and methods have been evaluated to mitigate the risk of transfusion-related disease transmission in blood products containing platelets. In addition to the screening and detection of pathogens and the subsequent elimination of contaminated blood products, a method for combining treatment to inactivate possible pathogens (i.e., pathogen inactivation) can also be utilized. Ideally, such a process results in the inactivation of many pathogens, such as viruses, bacteria, and parasites that may be present in blood products. In certain embodiments, the method for pathogen inactivation requires adding a certain amount of pathogen inactivation compounds (e.g., processing platelet preparations) to platelet preparations. For example, pathogen inactivation may involve adding low molecular weight compounds that inactivate various pathogens, wherein a specific method involves adding a photosensitizer, which will inactivate a variety of pathogens that may be present when activated by light illumination using a suitable wavelength. Two commercially available methods include adding aminostalin or riboflavin to platelets, and then illuminating with UV light. Other methods include irradiation with UV light without the addition of a photosensitizer, and irradiation with other photoactive compounds, including psoralen derivatives other than amitosalin, isoalloxazines other than riboflavin, alloxazines, dyes such as phthalocyanines, phenothiazine dyes (e.g., methylene blue, azure B, azure C, thionine, toluidine blue), porphyrin derivatives (e.g., dihematoporphyrin ethers, hematoporphyrin derivatives, benzene-porphyrin derivatives, alkyl-substituted sapphyrins) and merocyanine 540 (Prodouz et al., Blood Cells 1992, 18(1): 101-14; Sofer, Gail, BioPharm, August 2002). Other pathogen inactivation systems include, for example, those described in PCT Publication Nos. WO 2012071135; WO 2012018484; WO 2003090794; WO 2003049784; WO 1998018908; WO 1998030327; WO 1996008965; WO 1996039815; WO 1996039820; WO1996040857; WO 1993000005; US Patent Application No. US20050202395; and US Patent Nos. 8296071 and 6548242, the disclosures of which are incorporated herein by reference as they relate to pathogen inactivation in blood products. In some embodiments, the pathogen-inactivating compound is a photoactivated pathogen-inactivating compound selected from the group consisting of psoralens, isoalloxazines, alloxazines, phthalocyanines, phenothiazines, porphyrins, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen. In some embodiments, the pathogen-inactivating compound is amitosaline.In cases where a compound is added to platelets for pathogen inactivation, whether or not the method requires illumination, in some cases it may be desirable to remove any residual pathogen inactivating compound or its byproducts (eg, photoproducts).

[0129] The methods for pathogen inactivation and removal of pathogen inactivating compounds described herein are applicable to any platelet preparation, whether the platelet preparation comprises individual platelet donations (eg, apheresis-collected platelets) or a pooled platelet preparation.

[0130] Some pathogen inactivation methods disclosed herein may not require the use of a removal device (i.e., a device for reducing the concentration of pathogen inactivating compounds, such as small organic compounds and their byproducts in platelet preparations) while substantially maintaining the desired biological activity of the platelets.

[0131] Some pathogen inactivation methods may require the use of a removal device (i.e., a device for reducing the concentration of a pathogen-inactivating compound, such as a small organic compound and its byproducts in a platelet preparation) while substantially maintaining the desired biological activity of the platelets. In some embodiments, the removal device is referred to as a compound adsorption device (CAD) and may include a container (e.g., a CAD container, a CAD bag) that includes one or more materials, such as adsorbent particles, and is suitable for also containing a platelet preparation, from which the concentration of the pathogen-inactivating compound and its byproducts is reduced. Such a removal device is typically intended to be used in a batch mode, i.e., the device is placed in contact with the platelets and continuously in contact with the removal device, for example, by shaking, so that over the contact time, substantially the entire platelet solution is in contact with the removal device, resulting in a reduction in the level of the pathogen-inactivating compound. Such batch devices require the use of adsorbent particles that bind to the pathogen-inactivating compound and can be used by adding the adsorbent particles directly to the platelet container (e.g., bag) after illumination or transferring the platelets to a bag containing the adsorbent particles after illumination, and then agitating the platelets for a specified period of time to contact the platelet preparation with the removal device. Although free adsorbent particles can be used as the removal device, such particles can be contained in a mesh bag, such as a polyester or nylon mesh bag, which allows the platelet solution to contact the adsorbent particles while the particles are contained in the bag. Alternatively, the adsorbent particles can be fixed in a matrix, wherein the fixed matrix can be directly present in the blood bag used for batch removal, or can be similarly contained in a mesh bag. In some cases, the removal device contains porous adsorbent particles in an amount sufficient to reduce the pathogen-inactivating compound to below the desired concentration, wherein the adsorbent particles have an affinity for the pathogen-inactivating compound, wherein it should be understood that such adsorbent particles can be selected so as to optimally adsorb one or more compounds to be removed while minimizing the impact on those components that should not be removed or damaged by contact with the adsorbent particles. A variety of adsorbent particles are known, generally including particles made of any natural or synthetic material capable of interacting with the compound to be removed, including particles made of natural materials, such as activated carbon, silica, diatomaceous earth and cellulose; and synthetic materials, such as hydrophobic resins, hydrophilic resins or ion exchange resins. Such synthetic resins include, for example, carbonaceous materials, polystyrene, polyacrylic acid, polyacrylates, cation exchange resins and polystyrene-divinylbenzene. Detailed descriptions of such removal devices suitable for use in the methods described in this specification can be found in PCT Publication Nos. WO 1996040857, WO 1998030327, WO 1999034914 and WO 2003078023, and the disclosures of the above publications regarding such removal devices and adsorbent particles and other materials used to prepare such devices are incorporated into this specification by reference.Exemplary adsorbent particles include, but are not limited to, Amberlite (Rohm and Haas) XAD-2, XAD-4, XAD-7, XAD-16, XAD-18, XAD-1180, XAD-1600, XAD-2000, XAD-2010; Amberchrom (Toso Haas) CG-71m, CG-71c, CG-161m, CG161c; Diaion Sepabeads (Mitsubishi Chemicals) HP20, P206, SP207, SP850, HP2MG, HP20SS, SP20MS; Dowex (Dow Chemical) XUS-40285, XUS-40323, XUS-43493 (also known as Optipore V493 (dry form) or Optipore L493 (hydrated form)), Optipore V503, Optipore SD-2; Hypersol Macronet (Purolite) MN-100, MN-102, MN-150, MN-152, MN-170, MN-200, MN-202, MN-250, MN-252, MN-270, MN-300, MN-400, MN-500, MN-502, Purosorb (Purolite) PAD350, PAD 400, PAD 428, PAD 500, PAD 550, PAD 600, PAD 700, PAD 900 and PAD 950. The material used to form the immobilization matrix comprises a low melting point polymer, such as nylon, polyester, polyethylene, polyamide, polyolefin, polyvinyl alcohol, ethylene vinyl acetate or polysulfone. In one example, the adsorbent particles fixed in the matrix are in the form of a sintered medium. Although it is understood that the methods, kits and compositions described in this specification may include removal devices known in the art, a commercially available removal device for aminopalin-inactivated platelet product can be used to illustrate such methods and devices. Such removal devices include Hypersol Macronet MN-200 adsorbent contained in a sintered matrix, wherein the sintered matrix includes PL2410 plastic as a binder. In one embodiment, the removal device includes Hypersol Macronet MN-200 adsorbent in a sintered matrix including PL2410, wherein the amount of Hypersol Macronet MN-200 is about 5-50 grams, about 5-10 grams, about 10-15 grams, about 15-20 grams, about 20-25 grams, about 25-30 grams, about 30-35 grams, about 35-40 grams, about 40-45 grams, or about 45-50 grams of dry weight equivalents.

[0132] Because various resins may require different treatments when used to prepare removal devices that can be used in the methods, kits and compositions described in this specification, unless otherwise stated, the comparison of the amount of adsorbent resin described in this specification is a comparison of the dry weight of the resin. For example, the resin is dried to <5% water before processing, and the amount of resin used is compared using an equal amount of adsorbent dry weight. For example, Hypersol Macronet MN-200 is treated to stabilize the adsorbent or typically referred to as a so-called wet adsorbent so that it can be used directly when in contact with a platelet unit. Such a wet sample can include, for example, about 50% glycerol or other suitable wetting agents. In some embodiments, the adsorbent resin is a polystyrene-divinylbenzene resin. In some embodiments, the polystyrene-divinylbenzene resin is HypersolMacronet MN-200. In some embodiments, the adsorbent is contained in a sintered matrix, wherein the hot pressed matrix contains a PL2410 binder. In some embodiments, the Hypersol Macronet MN-200 adsorbent is contained in a hot pressed matrix to obtain a removal device.

[0133] In some embodiments of any of the methods, kits, and compositions described herein, one or more components (e.g., container, CAD, PIC) may be derived from or substantially similar to commercially available pathogen inactivation systems, e.g. Blood system (Cerus). It is well known in the art The blood system is a pathogen-inactivating system that has been widely used in blood collection centers in Europe and is FDA-approved in the United States. Blood system and pathogen inactivation methods and related compositions, see, for example, U.S. Patent Nos. 5399719, 5556993, 5578736, 5585503, 5593823, 5625079, 5654443, 5712085, 5871900, 5972593, 6004741, 6004742, 6017691, 6194139, 6218100,

[0134] 6503699, 6544727, 6951713, 7037642 and 7611831; and PCT Publication Nos. WO 1995000141, WO1996014739, WO1997021346, WO1998030327, WO1999034914 and WO1999034915. Since these patent documents relate to the inactivation of pathogens in blood products, the contents of each of their disclosures are incorporated into this specification by reference.

[0135] Kit for preparing platelet composition

[0136] In some aspects, the present disclosure provides a kit, such as a processing kit, for preparing a platelet composition according to any of the methods disclosed in this specification. In some embodiments, the kit is a disposable processing kit.

[0137] In some embodiments, the kit comprises (a) a first container comprising a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) instructions for preparing the platelet composition.

[0138] The kit for preparing a platelet composition (e.g., a pathogen-inactivated platelet composition) disclosed in the present specification includes a solution containing a platelet additive solution (PAS) and a pathogen-inactivating compound (PIC), wherein the solution containing PAS and PIC has a sufficient volume for preparing any number of platelet compositions (e.g., platelet units or therapeutic doses). In some embodiments, the kit comprises two or more first containers, wherein each of the two or more first containers comprises a different volume of a solution containing a platelet additive solution (PAS) and a pathogen-inactivating compound (PIC), and one of the two or more first containers can be selected for use based on the number or volume of the platelet composition to be prepared. In some embodiments, the kit comprises three first containers, one of which comprises a sufficient volume of a solution comprising (PAS) and a pathogen inactivating compound (PIC) for preparing one platelet composition (e.g., platelet unit, therapeutic dose), another first container comprises a sufficient volume of a solution comprising (PAS) and a pathogen inactivating compound (PIC) for preparing two platelet compositions, and another first container comprises a sufficient volume of a solution comprising (PAS) and a pathogen inactivating compound (PIC) for preparing three platelet compositions. When the kit is used in any of the methods provided in this specification, one of the three first containers can be selected for use based on the number of platelet compositions prepared.

[0139] In some embodiments, the kit for preparing a platelet composition comprises: (a) a first container comprising a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing a mixture of a platelet preparation and a solution comprising PAS and PIC, wherein the first container is not connected to the second container. In some embodiments, the first container is suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the first container is suitable for subjecting the platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the first container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing a platelet composition. In some embodiments, the first container is configured so as to be connected as a whole to a second container (e.g., by a soft plastic tube). In some embodiments, the first container is configured to be connected to the second container in an aseptic manner. In some embodiments, the kit also includes one or more components (e.g., tube, soft plastic tube) to connect the first container to the second container. In some embodiments, the kit for preparing platelet compositions also includes at least one (e.g., 1, 2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the second container. In some embodiments, the at least one storage container is integrally connected to the second container (e.g., by a soft plastic tube). In some embodiments, the at least one storage container is sealed, but has an openable flow path to the second container. In some embodiments, the at least one storage container is aseptically connected to the second container. In some embodiments, the first container is suitable for being connected to a single blood collection device or is connected to a container comprising a platelet preparation.

[0140] In some embodiments, a kit for preparing a platelet composition comprises: (a) a first container comprising a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing a mixture of a platelet preparation and a solution comprising PAS and PIC, wherein the first container is not connected to the second container. In some embodiments, the first container is suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the second container is suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the second container is suitable for subjecting the platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing a platelet composition. In some embodiments, the first container is configured to be connected to the second container as a whole (for example, by a soft plastic tube). In some embodiments, the first container is configured to be connected to the second container in an aseptic manner. In some embodiments, the test kit also includes one or more components (for example, tubes, soft plastic tubes) so that the first container is connected to the second container. In some embodiments, the test kit for preparing platelet compositions also includes at least one (for example, 1, 2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the second container. In some embodiments, the at least one storage container is connected to the second container as a whole (for example, by a soft plastic tube). In some embodiments, the at least one storage container is sealed, but has an openable flow path to the second container. In some embodiments, the at least one storage container is aseptically connected to the second container. In some embodiments, the first container is suitable for being connected to a single blood collection device or being connected to a container containing a platelet preparation.

[0141] In some embodiments, the kit for preparing a platelet composition comprises: (a) a first container comprising a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing a mixture of a platelet preparation and a solution comprising PAS and PIC, wherein the first container is not connected to the second container. In some embodiments, the first container is suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the second container is suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the second container is suitable for subjecting the platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is made of a material that is substantially translucent within a photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the first container is configured so as to be connected as a whole to a second container (e.g., by a soft plastic tube). In some embodiments, the first container is configured to be connected to the second container in an aseptic manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the first container to the second container. In some embodiments, the kit for preparing platelet compositions further comprises a third container, wherein the third container comprises a compound adsorption device (CAD), and wherein the third container is connected to the second container. In some embodiments, the third container is connected to the second container as a whole (e.g., by a soft plastic tube). In some embodiments, the third container is sealed, but has an openable flow path to the second container. In some embodiments, the third container is aseptically connected to the second container. In some embodiments, the third container is suitable for storing platelet compositions. In some embodiments, the kit for preparing platelet compositions further comprises at least one (e.g., 1, 2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the third container. In some embodiments, the at least one storage container is connected to the third container as a whole (e.g., by a soft plastic tube). In some embodiments, the at least one storage container is sealed, but has an openable flow path to the third container. In some embodiments, the at least one storage container is aseptically connected to the third container. In some embodiments, the first container is suitable for connection to an apheresis device or to a container containing a platelet preparation.

[0142] In some embodiments, the kit for preparing a platelet composition comprises: (a) a first container comprising a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing a mixture of a platelet preparation and a solution comprising PAS and PIC, wherein the first container is not connected to the second container. In some embodiments, the second container is suitable for mixing the platelet preparation with a solution comprising PAS and PIC. In some embodiments, the second container is suitable for subjecting the platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the second container comprises a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing platelet compositions. In some embodiments, the first container is configured so as to be connected as a whole to the second container (e.g., by a soft plastic tube). In some embodiments, the first container is configured to be connected to the second container in an aseptic manner. In some embodiments, the kit also includes one or more components (e.g., tube, soft plastic tube) to connect the first container to the second container. In some embodiments, the kit for preparing platelet compositions also includes at least one (e.g., 1, 2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the second container. In some embodiments, the at least one storage container is integrally connected to the second container (e.g., by a soft plastic tube). In some embodiments, the at least one storage container is sealed, but has an openable flow path to the second container. In some embodiments, the at least one storage container is aseptically connected to the second container. In some embodiments, the second container is suitable for being connected to a single blood collection device or being connected to a container comprising a platelet preparation.

[0143] In some embodiments, a kit for preparing a platelet composition comprises: (a) a first container comprising a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing a mixture of a platelet preparation and a solution containing PAS and PIC, wherein the first container is not connected to the second container. In some embodiments, the second container is suitable for mixing the platelet preparation with a solution containing PAS and PIC. In some embodiments, the second container is suitable for subjecting the platelet preparation mixed with a solution containing PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is made of a material that is substantially translucent within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the first container is configured so that it is connected to the second container as a whole (e.g., by a soft plastic tube). In some embodiments, the first container is configured to be connected to the second container in a sterile manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the first container to the second container. In some embodiments, the kit for preparing platelet compositions also includes a third container, wherein the third container includes a compound adsorption device (CAD), and wherein the third container is connected to the second container. In some embodiments, the third container is connected to the second container as a whole (for example, by a soft plastic tube). In some embodiments, the third container is sealed, but has an openable flow path to the second container. In some embodiments, the third container is aseptically connected to the second container. In some embodiments, the third container is suitable for storing platelet compositions. In some embodiments, the kit for preparing platelet compositions also includes at least one (for example, 1, 2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the third container. In some embodiments, the at least one storage container described is connected to the third container as a whole (for example, by a soft plastic tube). In some embodiments, the at least one storage container described is sealed, but has an openable flow path to the third container. In some embodiments, the at least one storage container described is aseptically connected to the third container. In some embodiments, the second container is suitable for being connected to a single blood component collection device or to a container containing platelet preparations.

[0144] In some embodiments, a kit for preparing a platelet composition comprises (a) a first container comprising a platelet additive solution (PAS); (b) a second container comprising a pathogen inactivating compound (PIC); and (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC, wherein the first container and the second container are connected to each other, and wherein none of the first container and the second container is connected to the third container. In some embodiments, the first container and the second container are configured to have a sealed but openable flow path between each other. In some embodiments, the first container is configured to be connected to the third container as a whole (e.g., by a soft plastic tube). In some embodiments, the first container is configured to be connected to the third container in an aseptic manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the first container to the third container. In some embodiments, the second container is configured to be connected to the third container as a whole (e.g., by a soft plastic tube). In some embodiments, the second container is configured to be connected to the third container in an aseptic manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the second container to the third container. In some embodiments, the second container is configured to be connected to the third container as a whole (e.g., by a soft plastic tube). In some embodiments, the second container is configured to be connected to the third container in an aseptic manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the second container to the third container. In some embodiments, the first container is suitable for merging PAS and PIC. In some embodiments, the second container is suitable for merging PAS and PIC. Any one or more of the first container, the second container, and the third container can be suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the first container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the third container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). Any one or more of the first container, the second container, and the third container can be made of a material that is substantially semi-transmitting light within a photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the third container comprises a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing platelet compositions. In some embodiments, the kit for preparing platelet compositions further comprises at least one (e.g., 1, 2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the third container. In some embodiments, the at least one storage container is integrally connected to the third container (e.g., by a soft plastic tube). In some embodiments, the at least one storage container is sealed, but has an openable flow path that reaches the third container.In some embodiments, the at least one storage container is aseptically connected to the third container.Any one or more of the first container, the second container, and the third container may be adapted to be connected to an apheresis device or to a container containing a platelet preparation.

[0145] In some embodiments, a kit for preparing a platelet composition comprises (a) a first container comprising a platelet additive solution (PAS), (b) a second container comprising a pathogen inactivating compound (PIC) and (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC, wherein the first container and the second container are connected to each other, and wherein none of the first container and the second container is connected to the third container. In some embodiments, the first container and the second container are configured to have a sealed but openable flow path between each other. In some embodiments, the first container is configured so that the entire container is connected to the third container (e.g., by a soft plastic tube). In some embodiments, the first container is configured to be connected to the third container in an aseptic manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the first container to the third container. In some embodiments, the second container is configured so that the entire container is connected to the third container (e.g., by a soft plastic tube). In some embodiments, the second container is configured to be connected to the third container in an aseptic manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the second container to the third container. In some embodiments, the second container is configured to be connected to the third container in an aseptic manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the second container to the third container. In some embodiments, the first container is suitable for merging PAS and PIC. In some embodiments, the second container is suitable for merging PAS and PIC. Any one or more of the first container, the second container, and the third container can be suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the first container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the third container is suitable for subjecting a platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). Any one or more of the first container, the second container, and the third container can be made of a material that is substantially semi-transmitting light within a photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the kit for preparing a platelet composition further comprises a fourth container, wherein the fourth container comprises a compound adsorption device (CAD). In some embodiments, the fourth container is configured so that the whole is connected to the third container (e.g., by a soft plastic tube). In some embodiments, the fourth container is configured to have an openable flow path that reaches the third container. In some embodiments, the fourth container is configured to be connected to the third container in an aseptic manner. In some embodiments, the test kit also includes one or more components (e.g., tube, soft plastic tube) so that the fourth container is connected to the third container.In some embodiments, the fourth container is suitable for storing platelet compositions. In some embodiments, the kit for preparing platelet compositions also includes at least one (for example, 1,2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the fourth container. In some embodiments, the at least one storage container is integrally connected to the fourth container (for example, by a soft plastic tube). In some embodiments, the at least one storage container is sealed but has an openable flow path to the fourth container. In some embodiments, the kit for preparing platelet compositions also includes at least one (for example, 1,2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the fourth container. Any one or more of the first container, the second container and the third container can be suitable for being connected to a single blood collection device or connected to a container comprising a platelet preparation.

[0146] In some embodiments, the kit for preparing a platelet composition comprises (a) a first container comprising a platelet additive solution (PAS), (b) a second container comprising a pathogen inactivating compound (PIC) and (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC, wherein none of the first container and the second container is connected to the third container. In some embodiments, the first container and the second container are configured to be connected to each other (e.g., connected in a sterile manner). In some embodiments, the kit further comprises one or more components (e.g., a tube, a soft plastic tube) so that the first container is connected to the second container. In some embodiments, the first container is configured so that the entire container is connected to the third container (e.g., through a soft plastic tube). In some embodiments, the first container is configured to be connected to the third container in a sterile manner. In some embodiments, the kit further comprises one or more components (e.g., a tube, a soft plastic tube) so that the first container is connected to the third container. In some embodiments, the second container is configured so that the entire container is connected to the third container (e.g., through a soft plastic tube). In some embodiments, the second container is configured to be connected to the third container in a sterile manner. In some embodiments, the kit further comprises one or more components (e.g., tubes, soft plastic tubes) to connect the second container to the third container. In some embodiments, the first container is suitable for merging PAS and PIC. In some embodiments, the second container is suitable for merging PAS and PIC. Any one or more of the first container, the second container, and the third container can be suitable for mixing a platelet preparation with a solution comprising PAS and PIC. In some embodiments, the first container is suitable for subjecting the platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the second container is suitable for subjecting the platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In some embodiments, the third container is suitable for subjecting the platelet preparation mixed with a solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). Any one or more of the first container, the second container, and the third container can be made of a material that is substantially semi-transmitting light within the photochemical inactivation wavelength range (e.g., about 200nm to about 400nm, ultraviolet A spectrum). In some embodiments, the third container comprises a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing platelet compositions. In some embodiments, the kit for preparing platelet compositions also comprises at least one (e.g., 1, 2 or 3) storage container, wherein the at least one storage container is suitable for storing platelet compositions, and wherein the at least one storage container is connected to the third container. In some embodiments, the at least one storage container is integrally connected to the third container (e.g., by a soft plastic tube).In some embodiments, the at least one storage container is sealed but has an openable flow path to the third container. In some embodiments, the at least one storage container is aseptically connected to the third container. Any one or more of the first container, the second container, and the third container can be suitable for connection to a single blood component device or to a container containing a platelet preparation.

[0147] In some embodiments of any kit described in this specification, the solution of PAS and PIC has a volume of about 10mL to about 1000mL. In some embodiments, the solution of PAS and PIC has a volume of about 200mL to about 900mL, about 300mL to about 800mL, about 400mL to about 700mL or about 500mL to about 600mL. In some embodiments, the solution of PAS and PIC has a volume of about 100mL, about 200mL, about 300mL, about 400mL, about 500mL, about 600mL, about 700mL, about 800mL, about 900mL or about 1000mL. In some embodiments, the solution of PAS and PIC has a volume of less than about 1000mL, less than about 800mL, less than about 600mL, less than about 500mL, less than about 400mL, less than about 300mL, less than about 200mL, less than about 100mL or less than about 50mL. In some embodiments, the solution of PAS and PIC has a volume greater than about 800 mL, greater than about 600 mL, greater than about 500 mL, greater than about 400 mL, greater than about 300 mL, greater than about 200 mL, greater than about 100 mL, greater than about 50 mL, or greater than about 10 mL.

[0148] In some embodiments of any of the kits described herein, the concentration of PIC in the PAS and PIC solution is about 25 μM to about 1200 μM, about 50 μM to about 1000 μM, about 50 μM to about 750 μM, about 50 μM to about 500 μM, about 75 μM to about 500 μM, about 100 μM to about 400 μM, about 150 μM to about 350 μM, about 200 μM to about 300 μM, or about 225 μM to about 250 μM. In some embodiments, the PIC concentration is about 25 μM, about 50 μM, about 75 μM, about 100 μM, about 125 μM, about 150 μM, about 175 μM, about 200 μM, about 250 μM, about 275 μM, about 300 μM, about 325 μM, about 350 μM, about 375 μM, about 400 μM, about 450 μM, about 500 μM, about 550 μM, about 600 μM, about 650 μM, about 700 μM, about 750 μM, about 800 μM, about 850 μM, about 900 μM, about 1000 μM, about 1100 μM, about 1200 μM, about 1300 μM, about 1400 μM, or about 1500 μM. In some embodiments, the PIC concentration is about 225 μM to about 235 μM. In some embodiments, the PIC concentration is about 225 μM, about 226 μM, about 227 μM, about 228 μM, about 229 μM, about 230 μM, about 231 μM, about 232 μM, about 233 μM, about 234 μM, or about 235 μM.

[0149] In some embodiments of any kit described in this specification, the PIC is psoralen. In some embodiments of any kit described in this specification, the PIC is amitosaline. In some embodiments of any kit described in this specification, the PIC is selected from isoalloxazines, alloxazines, phthalocyanines, phenothiazines, porphyrins, merocyanine 540 and salts or free bases thereof.

[0150] A non-limiting example of a kit for preparing a platelet composition according to the methods disclosed in this specification is exemplified in Figures 1A-1E and 2A-2E.

[0151] Figure 1A The exemplary kit 100 shown in FIG. 1 includes: (a) a first container 105 containing a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container 110 (e.g., a platelet container), wherein the first container 105 is not connected to the second container 110. Dashed lines 115, 120 indicate that the platelet preparation can be added to the solution first container 105 containing a solution containing PAS and PIC or the platelet preparation can be added to the second container 110. Figure 1AThe first container 105 shown in FIG. 1 is suitable for mixing a platelet preparation with a solution comprising PAS and PIC and optionally for subjecting the platelet preparation mixed with the solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens, if present. Figure 1A The second container 110 shown in is suitable for mixing the platelet preparation with the solution comprising PAS and PIC and is suitable for containing a mixture of the platelet preparation and the solution comprising PAS and PIC. In addition, the second container 110 is suitable for one or more of the following: subjecting the platelet preparation mixed with the solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present); containing a compound adsorption device (CAD); and storing the platelet composition. In some embodiments, Figure 1A The exemplary kit shown in does not include CAD.

[0152] Figure 1B Another alternative structure of an exemplary kit 101 of the present disclosure is shown in FIG. This structure optionally also includes a third container 125 connected to the second container 110 (e.g., via a sterile tube 135), wherein the third container 125 contains a compound adsorption device (CAD) 130. Figure 1B As shown in , the second container 110 is suitable for subjecting the platelet preparation mixed with the solution containing PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In addition, the third container 125 is optionally suitable for storing the platelet composition.

[0153] Figure 1C Another alternative configuration of an exemplary kit 102 of the disclosed invention is shown in . This configuration optionally also includes a fourth container 140 suitable for storing a platelet composition, wherein the third container 125 containing a compound adsorption device (CAD) 130 is connected to the fourth container 140 (e.g., by a sterile tube 145).

[0154] Figure 1D Another alternative configuration of an exemplary kit 103 of the disclosed invention is shown in . This configuration optionally further includes at least one storage container 140, 150, 155, wherein at least one storage container 140, 150, 155 is suitable for storing a platelet composition, and wherein the at least one storage container 140, 150, 155 is connected to a third container 125 containing a compound adsorption device (CAD) 130 (e.g., via a sterile tube 146).

[0155] Figure 1E Another alternative structure of an exemplary reagent kit 104 of the present disclosure is shown in FIG. Figure 1EAs shown in the figure, the first container 105 is suitable for mixing the platelet preparation with the solution comprising PAS and PIC, and is further suitable for subjecting the platelet preparation mixed with the solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens (if present) and the second container 110 comprises a compound adsorption device (CAD) 130. This structure also includes a third container 125 connected to the second container 110 (e.g., by a sterile tube 135), wherein the third container 125 is optionally suitable for storing the platelet composition.

[0156] Figure 2A The exemplary kit 200, 201 shown in the Figure includes: (a) a first container 215, 225 containing a platelet additive solution (PAS); (b) a second container 205, 235 containing a pathogen inactivating compound (PIC); and (c) a third container (e.g., platelet container 220, 240) suitable for containing a platelet preparation mixed with PAS and PIC, wherein the first container and the second container are connected to each other (e.g., by a sealed, but openable flow path 210, 230), and wherein neither the first container nor the second container is connected to the third container. Dashed lines 250, 251, 252, 253, 254, 255 indicate that the platelet preparation can be added to the first container containing PAS, the platelet preparation can be added to the second container containing PIC, or the platelet preparation can be added to the third container. Figure 2A The first container (200 on the left side of the page) shown in FIG. 1 is suitable for combining AS with PIC and further mixing the platelet preparation. Alternatively, Figure 2A The second container (201 on the right side of the page) shown in the figure is suitable for combining PAS with PIC and further mixing the platelet preparation, and is optionally suitable for subjecting the platelet preparation mixed with the solution containing PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In addition, in either structure 200 or 201, the third container 220, 240 is suitable for one or more of the following: subjecting the platelet preparation mixed with the solution containing PAS and PIC to light sufficient to photochemically inactivate pathogens (if present); containing a compound adsorption device (CAD); and storing the platelet composition. In some embodiments, Figure 2A The exemplary kit shown in does not include CAD.

[0157] An alternative configuration 202 for an exemplary kit of the present disclosure is as follows: Figure 2B This structure optionally also includes a fourth container 265 connected to the third container 220 (e.g., via a sterile tube 270), wherein the fourth container 265 contains a compound adsorption device (CAD) 265. Figure 2BAs shown in FIG. 1 , the third container 220 is suitable for subjecting the platelet preparation mixed with the solution containing PAS and PIC to light sufficient to photochemically inactivate pathogens (if present). In addition, the fourth container 260 is optionally suitable for storing the platelet composition.

[0158] Another alternative configuration 203 for an exemplary kit of the present disclosure is as follows Figure 2C This structure optionally also includes a fifth container 275 suitable for storing a platelet composition, wherein the fourth container 260 containing a compound adsorption device (CAD) 265 is connected (eg, via a sterile tube 280) to the fifth container 275.

[0159] Another alternative configuration 204 for an exemplary kit of the present disclosure is as follows Figure 2D This structure optionally further includes at least one storage container 275, 285, 290, wherein at least one storage container 275, 285, 290 is suitable for storing a platelet composition, and wherein the at least one storage container 275, 285, 290 is connected (e.g., by a sterile tube 281) to a fourth container 260 comprising a compound adsorption device (CAD) 265.

[0160] Another alternative configuration 206 for an exemplary kit of the present disclosure is as follows Figure 2E As shown in Figure 2E As shown in the figure, the first container 205 is suitable for combining PAS with PIC and further mixing platelets. The third container 220 contains a compound adsorption device (CAD) 265. This structure also includes a fourth container 260 connected to the third container 220 (e.g., by a sterile tube 270), wherein the fourth container 260 is optionally suitable for storing a platelet composition.

[0161] As disclosed in this specification, platelet preparations can be prepared by apheresis. Figure 3 As shown, the apheresis device can be connected to any kit disclosed in this specification as a source of platelet preparation (e.g., platelets collected from a donor using the apheresis device), wherein examples of connection points in the apheresis device are described. The kits disclosed in this specification can be used with any apheresis device, including those disclosed in U.S. Patent No. 5,868,696. For example, Figures 1A-1E As shown, the apheresis device can be connected to: a first container, which includes a solution containing PAS and PIC; and / or a second container. In other exemplary embodiments, as Figure 2A-2EAs shown, the apheresis device can be connected to one or more of: a first container containing a PAS; a second container containing a PIC; and a third container.

[0162] Composition

[0163] In some aspects, the present disclosure provides a composition comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC), wherein the composition is platelet-free.

[0164] In some embodiments of the composition comprising PAS and PIC, wherein the composition is platelet-free, the PAS comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

[0165] In some embodiments of the composition comprising PAS and PIC, wherein the composition is platelet-free, the PIC is psoralen. In some embodiments of the composition comprising PAS and PIC, wherein the composition is platelet-free, the PIC is amitosaline. In some embodiments of the composition comprising PAS and PIC, wherein the composition is platelet-free, the PIC is selected from the group consisting of isoalloxazines, alloxazines, phthalocyanines, phenothiazines, porphyrins, merocyanine 540, and salts or free bases thereof.

[0166] In some embodiments of the composition comprising PAS and PIC, wherein the composition does not contain platelets, the solution comprising PAS and PIC has a volume of about 100 mL to about 1000 mL. In some embodiments, the solution comprising PAS and PIC has a volume of about 200 mL to about 900 mL, about 300 mL to about 800 mL, about 400 mL to about 700 mL, or about 500 mL to about 600 mL. In some embodiments, the solution comprising PAS and PIC has a volume of about 100 mL, about 200 mL, about 300 mL, about 400 mL, about 500 mL, about 600 mL, about 700 mL, about 800 mL, about 900 mL, or about 1000 mL. In some embodiments, the solution comprising PAS and PIC has a volume of less than about 1000 mL, less than about 800 mL, less than about 600 mL, less than about 500 mL, less than about 400 mL, less than about 300 mL, or less than 200 mL. In some embodiments, the solution comprising PAS and PIC has a volume of greater than about 800 mL, greater than about 700 mL, greater than about 600 mL, greater than about 500 mL, greater than about 400 mL, greater than about 300 mL, greater than about 200 mL, or greater than about 100 mL. In some embodiments, the solution comprising PAS and PIC has a volume of about 1000 mL to about 5000 mL.

[0167] In some embodiments of the composition comprising PAS and PIC, wherein the composition is platelet-free, the concentration of PIC in the solution comprising PAS and PIC is about 25 μM to about 1200 μM, about 50 μM to about 1000 μM, about 50 μM to about 750 μM, about 50 μM to about 500 μM, about 75 μM to about 500 μM, about 100 μM to about 400 μM, about 150 μM to about 350 μM, about 200 μM to about 300 μM, or about 225 μM to about 250 μM. In some embodiments, the concentration of PIC in the solution comprising PAS and PIC is about 25 μM, about 50 μM, about 75 μM, about 100 μM, about 125 μM, about 150 μM, about 175 μM, about 200 μM, about 250 μM about 275 μM, about 300 μM, about 325 μM, about 350 μM, about 375 μM, about 400 μM, about 450 μM, about 500 μM, about 550 μM, about 600 μM, about 650 μM, about 700 μM, about 750 μM, about 800 μM, about 850 μM, about 900 μM, about 1000 μM, about 1100 μM, about 1200 μM, about 1300 μM, about 1400 μM, or about 1500 μM. In some embodiments, the concentration of PIC in the solution comprising PAS and PIC is about 225 μM to about 235 μM. In some embodiments, the concentration of PIC in the solution comprising PAS and PIC is about 225 μM, about 226 μM, about 227 μM, about 228 μM, about 229 μM, about 230 μM, about 231 μM, about 232 μM, about 233 μM, about 234 μM, or about 235 μM.

[0168] In some embodiments, the composition comprising PAS and PIC is a stock solution, wherein the composition is free of platelets.

[0169] In some embodiments, the composition comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) is sterile, wherein the composition is free of platelets.

[0170] In some aspects, the present disclosure also provides platelet compositions prepared by any of the methods described in this specification.

[0171] The disclosed embodiments and embodiments disclosed in this specification further describe methods, kits and compositions for preparing platelet compositions suitable for input into individuals. The components and steps shown are set forth to explain the exemplary embodiments shown, and it should be expected that ongoing technological developments will change the way specific functions are performed. The embodiments presented in this specification are for illustrative rather than limiting purposes. In addition, for ease of description, the boundaries of the functional building blocks have been arbitrarily defined in this specification. Alternative boundaries may be defined as long as specific functions and their relationships are appropriately performed. Based on the teachings contained in this specification, alternatives (including equivalents, extensions, variations, deviations, etc. of the solutions described in this specification) are obvious to those skilled in the relevant art. These alternatives all fall within the scope and spirit of the disclosed embodiments.

[0172] The words "comprising", "having", "containing", "including" and other similar forms used in this specification are intended to be equivalent and open-ended, and the one or more items following any of these words do not mean an exhaustive list of such one or more items, nor are they limited to the one or more items listed. For example, an article "comprising" components A, B, and C may consist of (i.e., only contain) components A, B, and C, or may contain not only components A, B, and C, but also one or more additional components. It should be understood that "comprising" and its grammatical equivalents include "consisting of" or "consisting essentially of".

[0173] Where a range of values ​​is provided, it is understood that each intervening value between the upper and lower limits of the range (to one-tenth of the unit of the lower limit unless the context clearly dictates otherwise) and any other stated or intervening value in the stated range is included in the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

[0174] In this specification, values ​​or parameters related to "about" include (and describe) variations related to the value or parameter itself. For example, descriptions related to "about X" include descriptions of "X".

[0175] As used in this specification and in the appended claims, the singular forms "a," "or," and "the" include plural referents unless the context clearly dictates otherwise.

[0176] Those skilled in the art will also understand that the form and details of the specific implementations described in this specification may be changed without departing from the scope of the disclosed invention. In addition, although various advantages, aspects and objects have been described with reference to various embodiments, the scope of the disclosed invention should not be limited by reference to such advantages, aspects and objects. Instead, the scope of the disclosed invention should be determined with reference to the appended claims.

[0177] The present disclosure is further illustrated by the following examples, which are not to be construed as limiting the scope or spirit of the present disclosure to the specific procedures described therein.

[0178] Example

[0179] Example 1: Stability of Amitosalin in Platelet Additive Solution

[0180] Initial studies evaluated the stability of the pathogen-inactivating compound amitosalin (S-59) formulated in platelet additive solution. A 230 μM solution of the psoralen compound S-59 (Irsch et al., Transfus Med Hemother, 38: 19-31 (2011)) was prepared in Inter-Sol PAS (Fenwal Inc.) and maintained at room temperature and ambient light conditions. The samples were subjected to HPLC analysis of S-59 and photoproducts at the times listed in Table 1. The results shown in Table 1 demonstrate the stability of S-59 in Inter-Sol PAS for a period of 78 hours in ambient light, with a loss of <6% of S-59 at 78 hours. The S-59 data are shown as concentration (μM) and peak area (S-59 UV) for relative comparison with any photoproducts detected by HPLC (Table 1). Peak D and Peak E photoproducts, as well as the process impurity decomposition product 4'-HMT, were also observed at 22 hours and 72 hours, respectively, and the peak area values ​​are shown (Table 1).

[0181] Table 1. HPLC analysis of S-59 and photochemical products

[0182] sample S-59μM S-59UV Peak D UV Peak E UV 4'-HMT UV T 0 237.49 3700.439 nd nd 4.924 5 hours 230.62 3593.309 nd nd 5.624 6 hours 229.50 3575.825 nd nd 5.090 22 hours 223.71 3485.467 8.419 nd 5.125 30 hours 226.56 3529.854 11.179 nd 5.334 47 hours 223.76 3486.293 18.500 nd 4.954 56 hours 220.82 3440.455 21.304 nd 4.742 72 hours 226.88 3534.894 27.171 4.344 4.839 78 hours 223.69 3485.093 28.960 4.623 4.793

[0183] Additional studies evaluated the stability of S-59 (aminosalen) pathogen inactivating compounds formulated in platelet additive solution (PAS) but shielded from ambient light. (Fenwal Inc.) and maintained at room temperature, protected from ambient light conditions. HPLC analysis of S-59 and photoproducts was performed on samples at the times listed in Table 2. The results shown in Table 2 demonstrate the stability of S-59 in InterSol PAS over a 77 hour period when protected from ambient light, with no loss of S-59 at 77 hours, expressed as concentration (μM) and peak area (UV). Peak D and Peak E photoproducts were not detected until 77 hours, while the process impurity decomposition product 4'-HMT was observed, with peak area values ​​shown (Table 2).

[0184] Table 2. HPLC analysis of S-59 and photochemical products

[0185] sample S-59μM S-59UV 4'-HMT UV T 0 228.82 3393.0647 3.8849 5.5 hours 232.74 3451.6489 3.7162 21.5 hours 231.93 3439.4907 4.3525 28.5 hours 230.72 3421.447 3.8628 45.5 hours 229.22 3399.0142 4.4036 53 hours 230.72 3421.4934 4.0582 44 hours 230.96 3425.1028 4.0199 77 hours 232.41 3446.6414 4.4268

[0186] Example 2: Stability of Amitosalin in 65% PAS with 35% plasma and platelets

[0187] Further studies evaluated the stability and photoconversion of amitosalin (S-59) in PAS supplemented with plasma and also containing platelets. S-59 was added to 65% PAS and 35% plasma (a suspended platelet preparation) were mixed and the suspension of the mixture was maintained in a platelet incubator during the study. Samples were taken for HPLC analysis at time 0, 5, 21, 29 and 48 hours, and the mixture was then used at 55 hours. 3J UVA light treatment, post-UVA samples were also analyzed by HPLC for S-59 and photoproducts. The results shown in Table 3 demonstrate the stability of S-59 in the PAS / plasma / platelet mixture, with concentrations (μM) and peak areas (UV) showing no loss of S-59 prior to the 55-hour UVA treatment. Peak D and Peak E photoproducts were not detected (Table 3). UVA light treatment with the 55-hour sample showed that after incubation of S-59 in PAS / plasma, the photoconversion of S-59 was efficient, with only 15.3% remaining in the post-UVA sample (Table 3).

[0188] Table 3. HPLC analysis of S-59 and photochemical products

[0189] sample S-59μM S-59UV T 0 148.12 1752.513 5 hours 149.30 1738.331 21 hours 147.81 1739.214 29 hours 148.04 1725.882 48 hours 148.06 1750.513 55 hours after UVA 22.71 274.897

[0190] Example 3: Stability of Amitosalin in PAS / Plasma Containing Platelets and Bacteria

[0191] Another study evaluated the 24-hour stability and photoconversion of amitosalin (S-59) in the presence of bacteria in a PAS containing plasma and platelets. Two ABO-matched platelet units in 100% plasma were combined, split into two units, and added PAS (e.g., 65 / 35). S-59 was added to the test unit at a concentration of 150 μM, but was not initially added to the control unit. A logarithmic culture of K. pneumoniae (~8 log cfu / mL) was added to the unit with a target of ~60 CFU / unit, and the unit was incubated for about 24 hours at 22°C in a platelet oscillator. At the end of the incubation, S-59 was also added to the control unit at the same concentration, and both the control and test units were exposed to UVA illumination. Samples were taken before and after UVA illumination for unit bacterial titer determination and HPLC. After illumination, both units were subjected to a CAD treatment step to remove residual amitosalin and photoproducts and stored on a platelet oscillator for 7 days to confirm that there was no bacterial growth.

[0192] As shown in Table 4, the concentration of S-59 was stable during the 24-hour incubation period, with efficient photoconversion after UVA treatment at 24 hours in both the control and test units. Therefore, the presence of K. pneumoniae did not adversely affect S-59 stability or photoconversion.

[0193] Table 4. Concentration of S-59 during 24 hours and after UVA treatment

[0194]

[0195] Photochemical inactivation of K. pneumoniae was also measured after UVA exposure, and the titer (log cfu / mL) results are shown in the table below. High levels of inactivation were observed for both the control and test units, indicating that there was no adverse effect on S-59 photochemical inactivation after 24 hours of storage in a mixture of PAS / plasma and platelets containing K. pneumoniae (Table 5).

[0196] Table 5. Inactivation of Klebsiella pneumoniae

[0197]

[0198] Example 4: Inactivation of Calicivirus Using Tosalin in PAS / Plasma

[0199] It has been previously shown that caliciviruses used as models of HEV, such as feline calicivirus (FCV), are highly resistant to photochemical inactivation by amitosalin (S-59), with titers reduced by only approximately 1.7-2.4 log 10(Irsch et al., Transfus Med Hemother, 38: 19-31 (2011)). Based on the results of Examples 1 and 2, indicating that amitosalin is stable in PAS and PAS / plasma, additional studies were conducted to evaluate the level of inactivation of Calicivirus FCV by S-59 after prolonged incubation in PAS / plasma. In this study, platelets in PAS / plasma (65% / 35%) were pooled to approximately 1320 mL, for a total of approximately 16 x 10 11 platelets and diluted the stock solution spiked with Calicivirus FCV at 1:100. A sample was taken from the platelet mixture spiked with FCV to determine the initial titer. The platelets spiked with FCV were then divided into 5 units, each approximately 260 mL, with each unit approximately 3.2 x 10 11 Each unit is at a concentration of about 150 μM (this concentration is S-59 was administered at concentrations commercially used for pathogen inactivation treatments in blood systems. Platelet units were incubated for 0, 2, 4, 8, or 24 hours after the addition of S-59. Control samples were taken at each time point for viral titer determination and HPLC analysis of S-59 concentrations before UV-UVA treatment and then ~3 J / cm 2 UVA light exposure was performed to complete the photochemical treatment process for all test samples. After UVA treatment, FCV inactivation of control samples and test samples was evaluated using a standard viral plaque assay. As shown in Table 6, incubation of S-59 / PAS / plasma for 2 hours or more prior to exposure to UVA resulted in a sharp increase in FCV inactivation levels to below the detection limit compared to the 0-time sample (no pre-incubation prior to UVA treatment). This data suggests another advantage of the disclosed invention, which allows platelets to be collected in a premixed pathogen inactivating compound and additive solution (e.g., S-59 / PAS) and "pre-incubated" prior to the next UV exposure step during the photochemical treatment process (Table 6).

[0200] Table 6. FCV inactivation

[0201]

[0202] *Inactivated to the limit of detection.

[0203] A recalculation of the above inactivation data normalized to FCV cocktail titer is shown in Table 7.

[0204] Table 7. Calibrated FCV inactivation

[0205]

[0206] *Inactivated to the limit of detection.

[0207] Another study was conducted to evaluate the level of FCV inactivation following prolonged incubation (e.g., preincubation) in PAS / plasma as the amount of S-59 decreased. In this study, platelets in PAS / plasma (65% / 35%) were spiked with FCV stock at a 1:100 dilution. The FCV-spiked platelets were then divided into 16 individual test units. Each unit was dosed with S-59 at a concentration of approximately 150 μM, 90 μM, 30 μM, or 15 μM. After the addition of S-59 to one of the four dosing groups, the platelet units in each dosing group were incubated for 0, 4, 8, or 24 hours prior to light exposure. Control samples were removed from each unit to determine viral titer and HPLC analysis of S-59 concentration prior to UVA treatment and then ~3 J / cm 2 The test samples were photochemically treated with UVA light exposure. After UVA treatment, the FCV inactivation of the control sample and the test sample was evaluated using a standard viral plaque assay. Table 8 shows the FCV titer (log PFU / mL) of each sample, while Table 9 shows the logV inactivation of each sample.

[0208] Table 8. FCV titer

[0209] Comparison 150μM 90μM 30μM 15μM 0 hours 5.84 4.33 4.90 4.91 5.65 4 hours 5.74 <0.22 <0.22 2.00 4.49 8 hours 5.86 <-0.48 <-0.48 <1.22 2.22 24 hours 5.80 <-0.48 <-0.30 <-0.22 0.52

[0210] Table 9. FCV inactivation

[0211] 150μM 90μM 30μM 15μM 0 hours 1.51 0.94 0.93 0.19 4 hours 5.62 5.62 3.84 1.35 8 hours 5.84 5.84 4.62 3.62 24 hours 5.84 5.84 5.62 5.32

[0212] The control titer of the 0 hour mixture was used for the overall log inactivation calculation (5.84 log / mL).

[0213] As shown in these data, pre-incubation of platelets containing FCV in S-59 / PAS / plasma before UVA illumination results in high levels of FCV inactivation, even with input of lower concentrations of S-59 pathogen inactivating compounds. In particular, pre-incubation for 4, 8 or 24 hours at 150 μM and 90 μM S-59 concentrations, pre-incubation for 8 or 24 hours at 30 μM S-59 concentrations, or pre-incubation for 24 hours at 15 μM S-59 concentrations results in FCV inactivation greater than 4 logs. In addition, pre-incubation for 4 hours at 30 μM S-59 concentrations results in FCV inactivation of almost 4 logs, while pre-incubation for 8 hours at 15 μM S-59 concentrations results in FCV inactivation greater than 3.5 logs. HPLC analysis was also performed to determine the amount (e.g., concentration) of S-59 remaining in the sample after UVA illumination and photoconversion (Table 10).

[0214] Table 10. Concentration of S-59 after UVA

[0215]

[0216] As shown in Table 10, the residual S-59 concentration after treatment for all S-59 dosing groups of pre-incubation was reduced, including reaching a level below 5 μM (e.g., 2 μM). These data show that pathogen inactivation treatment conditions can be achieved based on the methods provided in this specification, which result in high levels of inactivation (e.g., >4 logs) and effective S-59 photoconversion, with a residual S-59 concentration of only 2 μM.

[0217] Example 5. Pathogen-inactivated platelets prepared using premixed amitosalin / PAS

[0218] Pathogen-inactivated platelets are prepared using the kits and methods of the disclosed invention. More specifically, in one example for preparing a single unit, 3.9 x 10 11 platelets and transferred to approximately 165.8 mL via sterile connected tubes A container of PAS solution containing amitosaline at a concentration of about 231 μM (see, e.g., Figure 1C , 2C ). The container containing the diluted (eg, final) platelets and a mixture of amitosalin / PAS / plasma at a concentration of about 150 μM amitosalin is then aseptically connected to the "dry side" remainder of the processing kit (see, e.g., Figure 1C , 2C ), and the mixture was transferred to the illumination container by gravity flow. The blood system illuminator (Cerus Corp.) was used at about 3 J / cm 2 After UVA light treatment, the photochemically treated platelets are transferred to a CAD container to remove residual amitosalin and photoproducts and then transferred to a single storage container. In another example, pathogen-inactivated platelets are similarly prepared, but the amitosalin concentration is 50% lower (e.g., to obtain a mixture of platelets and amitosalin / PAS / plasma having a diluted (e.g., final) amitosalin concentration of about 75 μM).

[0219] Example 6. Pathogen-inactivated platelets prepared using premixed amitosalin / PAS

[0220] Pathogen-inactivated platelets are prepared using the kits and methods of the disclosed invention, wherein the amitosalin / PAS container is directly connected to the Apheresis device (Fenwal Inc.). More specifically, in one embodiment of preparing two platelet units (eg, double), amitosalin is added to a concentration of about 231 μM. 500 mL container of PAS solution (see, e.g., Figure 1C ) in a container such as Figure 3 , and sterilely connected to the apheresis device as shown in FIG. Approximately 7.6×10 11 platelets, and about 331.5 mL of amitosalin was automatically added by the device. PAS solution to obtain a mixture of platelets and amitosalin / PAS / plasma with a diluted (e.g., final) amitosalin concentration of about 150 μM. The platelet mixture is then transferred to The two collection bags of the device are then separated into two evenly distributed platelets. Next, the two bags are removed from the apheresis device and each is individually connected to the "dry side" remnants of two separate processing kits via sterile connections (see, e.g., Figure 1C ), and the mixture was transferred to the illumination container by gravity flow. The blood system illuminator (Cerus Corp.) was used at about 3 J / cm 2 After UVA light treatment, the photochemically treated platelets are transferred to a CAD container to remove residual amitosalin and photoproducts and then each transferred to a single storage container to yield two pathogen-inactivated platelet units. Alternatively, collection bags removed from an apheresis device can be combined into a single photosensitive container by aseptically connecting to the "dry side" remnant of the processing kit (see, e.g., Figure 1D ), but using two final storage bags and processed as described above, resulting in two pathogen-inactivated platelet units. In another example, pathogen-inactivated platelets are similarly prepared, but the amitosalin concentration is 50% lower (e.g., to obtain a mixture of platelets and amitosalin / PAS / plasma having a diluted (e.g., final) amitosalin concentration of about 75 μM).

[0221] Exemplary embodiments

[0222] Embodiment 1. A method for preparing a platelet composition, comprising:

[0223] (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container;

[0224] (b) mixing the solution of step (a) with a platelet preparation; and

[0225] (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby producing a platelet composition.

[0226] Embodiment 2. The method of Embodiment 1, wherein the mixing of step (b) occurs in the first container.

[0227] Embodiment 3. The method of Embodiment 1, wherein the mixing of step (b) occurs in a second container.

[0228] Embodiment 4. The method of Embodiment 1 or Embodiment 2, wherein subjecting the mixture to light of step (c) occurs in a first container.

[0229] Embodiment 5. The method of any of Embodiments 1-3, wherein subjecting the mixture to light of step (c) occurs in a second container.

[0230] Embodiment 6. The method of any one of embodiments 1-5, wherein the platelet preparation is prepared by an apheresis method.

[0231] Embodiment 7. The method of embodiment 6, wherein the method further comprises connecting the first container to the apheresis device before step (b).

[0232] Embodiment 8. The method of embodiment 6 or embodiment 7, wherein the second container is connected to an apheresis device.

[0233] Embodiment 9. The method of any one of embodiments 1-5, wherein the platelet preparation is prepared from one or more whole blood donations by a buffy coat method or a platelet rich plasma (PRP) method.

[0234] Embodiment 10. The method of any one of Embodiments 1-9, further comprising, after step (c):

[0235] (d) transferring the platelet composition to a third container.

[0236] Embodiment 11. The method of Embodiment 10, wherein the third vessel comprises a compound adsorption device (CAD).

[0237] Embodiment 12. The method of embodiment 10 or embodiment 11, wherein the third container is suitable for storing a platelet composition.

[0238] Embodiment 13. The method of any one of embodiments 1-12, wherein the solution of step (a) comprises PIC at a concentration of about 15 μM to about 1500 μM.

[0239] Embodiment 14. The method of any one of embodiments 1-13, wherein the PIC is psoralen.

[0240] Embodiment 15. The method of Embodiment 14, wherein the PIC is amitosaline.

[0241] Embodiment 16. The method of any one of Embodiments 1-15, wherein the platelet preparation comprises plasma, wherein the plasma comprises approximately 32-47% by volume of the mixture of step (b), and wherein the platelet additive solution comprises the remainder of the volume.

[0242] Embodiment 17. The method of embodiment 16, wherein the ratio of PAS to plasma in the mixture of step (b) is about 65:35 by volume.

[0243] Embodiment 18. The method of any one of embodiments 1-17, wherein the mixture of step (b) comprises PICs at a concentration sufficient to result in at least 1 log inactivation of the pathogen, if present.

[0244] Embodiment 19. The method of any one of embodiments 1-18, wherein the mixture of step (b) comprises PICs at a concentration sufficient to result in at least 4 log inactivation of the pathogen, if present.

[0245] Embodiment 20. The method of any one of embodiments 1-19, wherein the mixture of step (b) comprises PIC at a concentration of about 5 μM to about 500 μM.

[0246] Embodiment 21. The method of Embodiment 20, wherein the mixture of step (b) comprises PIC at a concentration of about 145 μM to about 155 μM.

[0247] Embodiment 22. The method of Embodiment 20, wherein the mixture of step (b) comprises PIC at a concentration of about 30 μM to about 90 μM.

[0248] Embodiment 23. The method of any of Embodiments 1-22, wherein the PAS comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

[0249] Embodiment 24. The method of any one of Embodiments 1-23, further comprising, before step (c):

[0250] (b1) incubating the mixture of step (b) for a period of 30 minutes to 24 hours.

[0251] Embodiment 25. The method of any one of embodiments 1-24, wherein the platelet composition comprises at least 2x10 11 Platelets.

[0252] Embodiment 26. The method of any one of Embodiments 1-25, wherein the method is sufficient to inactivate at least 1 log of the pathogen (if present), and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing to remove residual PIC or its photoproducts.

[0253] Embodiment 27. The method of any of Embodiments 1-26, wherein the method is sufficient to inactivate at least 1 log of the pathogen (if present), and wherein the platelet composition after step (c) is suitable for transfusion into a subject without transferring the platelet composition to a container comprising a compound adsorption device (CAD).

[0254] Embodiment 28. The method of any one of embodiments 1-27, wherein the method is sufficient to inactivate at least 1 log of the pathogen, if present, and wherein the platelet composition after step (c) comprises 5 μM or less of PIC.

[0255] Embodiment 29. The method of any one of Embodiments 1-28, wherein the method is sufficient to inactivate at least 4 logs of pathogens (if present), wherein the platelet composition after step (c) comprises 2 μM or less of PIC, and wherein the concentration of PIC in the mixture of the platelet preparation and the solution comprising PAS and PIC is about 15 μM to about 150 μM.

[0256] Embodiment 30. A method of preparing a platelet composition comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing the solution of step (a) with a platelet preparation; (c) incubating the platelet preparation with the mixture of the solution comprising PAS and PIC for a period of about 30 minutes to about 24 hours; and (d) subjecting the incubated mixture of step (c) to light sufficient to photochemically inactivate pathogens, if present, thereby producing a platelet composition, wherein:

[0257] (i) The method is sufficient to inactivate at least one log of the pathogen, if present;

[0258] (ii) the concentration of PIC in the mixture of the platelet preparation and the solution comprising PAS and PIC is from about 15 μM to about 150 μM; and

[0259] (iii) the platelet composition after subjecting the mixture of the platelet preparation and the solution comprising PAS and PIC to light comprises less than 5 μM PIC.

[0260] Embodiment 31. A kit for preparing a platelet composition, comprising:

[0261] (a) a first container comprising a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and

[0262] (b) a second container suitable for containing a mixture of a platelet preparation and a solution comprising PAS and PIC,

[0263] The first container is not connected to the second container.

[0264] Embodiment 32. The kit of embodiment 31, wherein the first container is suitable for mixing the platelet preparation with a solution comprising PAS and PIC.

[0265] Embodiment 33. The kit of embodiment 31 or embodiment 32, wherein the second container is suitable for mixing the platelet preparation with a solution comprising PAS and PIC.

[0266] Embodiment 34. The kit of any one of Embodiments 31-33, wherein the second container is suitable for subjecting the platelet preparation mixed with the solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

[0267] Embodiment 35. The kit of any one of Embodiments 31-34, wherein the first container is suitable for subjecting the platelet preparation mixed with the solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

[0268] Embodiment 36. The kit of any one of Embodiments 31-35, wherein the second container comprises a compound adsorption device (CAD).

[0269] Embodiment 37. The kit of any one of Embodiments 31-36, wherein the second container is suitable for storing a platelet composition.

[0270] Embodiment 38. The kit of any one of Embodiments 31-37, further comprising a third container, wherein the third container comprises a compound adsorption device (CAD), and wherein the third container is connected to the second container.

[0271] Embodiment 39. The kit of any one of Embodiments 31-38, further comprising at least one storage container, wherein the at least one storage container is suitable for storing a platelet composition, and wherein the at least one storage container is connected to the second container or to the third container, if the third container is present.

[0272] Embodiment 40. The kit of any one of embodiments 31-39, wherein the solution comprising PAS and PIC has a volume of about 100 mL to about 1000 mL.

[0273] Embodiment 41. The kit of any one of embodiments 31-40, wherein the PIC is at a concentration of about 15 μM to about 1500 μM.

[0274] Embodiment 42. The kit of any one of Embodiments 31-41, wherein the PIC is psoralen.

[0275] Embodiment 43. The kit of embodiment 42, wherein the PIC is amitosaline.

[0276] Embodiment 44. The kit of any one of Embodiments 31-43, wherein the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or to a container comprising a platelet preparation.

[0277] Embodiment 45. A kit for preparing a platelet composition, comprising:

[0278] (a) a first container comprising a platelet additive solution (PAS);

[0279] (b) a second container comprising a pathogen inactivating compound (PIC); and

[0280] (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC,

[0281] The first container and the second container are connected to each other, and neither the first container nor the second container is connected to the third container.

[0282] Embodiment 46. The kit of embodiment 45, wherein the second container is suitable for combining PAS and PIC.

[0283] Embodiment 47. The kit of embodiment 45, wherein the first container is suitable for combining PAS and PIC.

[0284] Embodiment 48. The kit of any one of Embodiments 45-47, wherein the second container is suitable for mixing the platelet preparation with PAS and PIC.

[0285] Embodiment 49. The kit of any one of embodiments 45-47, wherein the first container is suitable for mixing the platelet preparation with PAS and PIC.

[0286] Embodiment 50. The kit of any one of embodiments 45-47, wherein the third container is suitable for mixing the platelet preparation with PAS and PIC.

[0287] Embodiment 51. The kit of any one of Embodiments 45-50, wherein the third container is suitable for subjecting the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

[0288] Embodiment 52. The kit of any one of Embodiments 45-50, wherein the second container is suitable for subjecting the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

[0289] Embodiment 53. The kit of any one of Embodiments 45-50, wherein the first container is suitable for subjecting the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

[0290] Embodiment 54. The kit of any one of Embodiments 45-53, wherein the third container comprises a compound adsorption device (CAD).

[0291] Embodiment 55. The kit of any one of Embodiments 45-54, wherein the third container is suitable for storing a platelet composition.

[0292] Embodiment 56. The kit of any one of Embodiments 45-55, further comprising a fourth container, wherein the fourth container comprises a compound adsorption device (CAD), and wherein the fourth container is connected to the third container.

[0293] Embodiment 57. The kit of any one of Embodiments 45-56, further comprising at least one storage container, wherein the at least one storage container is suitable for storing a platelet composition, and wherein the at least one storage container is connected to the third container or to the fourth container, if the fourth container is present.

[0294] Embodiment 58. The kit of any one of Embodiments 45-57, wherein the PIC is psoralen.

[0295] Embodiment 59. The kit of embodiment 58, wherein the PIC is amitosaline.

[0296] Embodiment 60. The kit of any one of Embodiments 45-59, wherein the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or to a container comprising a platelet preparation.

[0297] Embodiment 61. A composition comprising a pathogen inactivating compound (PIC) and a platelet additive solution (PAS), wherein the composition is platelet-free.

[0298] Embodiment 62. The composition of embodiment 61, wherein the concentration of PIC is from about 15 μM to about 1500 μM.

[0299] Embodiment 63. The composition of embodiment 61 or embodiment 62, wherein the PIC is psoralen.

[0300] Embodiment 64. The composition of Embodiment 63, wherein the PIC is amitosaline.

[0301] Embodiment 65. The composition of any one of Embodiments 61-64, wherein the PAS comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

[0302] Embodiment 66. The composition of any one of Embodiments 61-65, wherein the composition is sterile.

[0303] Embodiment 67. A platelet composition prepared by the method of any one of embodiments 1-30.

Claims

1. A method for preparing a platelet composition, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) in a first container; (b) mixing the solution of step (a) with a platelet preparation; as well as (c) subjecting the mixture of step (b) to light sufficient to photochemically inactivate pathogens, if present, thereby producing a platelet composition.

2. The method of claim 1, wherein the mixing of step (b) occurs in the first container.

3. The method of claim 1, wherein the mixing of step (b) occurs in a second container.

4. The method of claim 1 or claim 2, wherein subjecting the mixture to light of step (c) occurs in a first container.

5. The method of any one of claims 1-3, wherein subjecting the mixture to light of step (c) occurs in a second container.

6. The method of any one of claims 1-5, wherein the platelet preparation is prepared by apheresis.

7. The method of claim 6, wherein the method further comprises connecting the first container to an apheresis device prior to step (b).

8. The method of claim 6 or claim 7, wherein the second container is connected to an apheresis device.

9. The method of any one of claims 1-5, wherein the platelet preparation is prepared from one or more whole blood donations by a buffy coat method or a platelet rich plasma (PRP) method.

10. The method of any one of claims 1 to 9, further comprising, after step (c): (d) transferring the platelet composition to a third container.

11. The method of claim 10, wherein the third vessel comprises a compound adsorption device (CAD).

12. The method of claim 10 or claim 11, wherein the third container is suitable for storing a platelet composition.

13. The method of any one of claims 1-12, wherein the solution of step (a) comprises PIC at a concentration of about 15 μM to about 1500 μM.

14. The method of any one of claims 1-13, wherein the PIC is psoralen.

15. The method of claim 14, wherein the PIC is amitosaline.

16. The method of any one of claims 1-15, wherein the platelet preparation comprises plasma, wherein the plasma comprises about 32-47% by volume of the mixture of step (b), and wherein the platelet additive solution comprises the remainder of the volume.

17. The method of claim 16, wherein the ratio of PAS to plasma in the mixture of step (b) is about 65:35 by volume.

18. The method of any one of claims 1 to 17, wherein the mixture of step (b) comprises PIC at a concentration sufficient to result in at least 1 log inactivation of the pathogen, if the pathogen is present.

19. The method of any one of claims 1 to 18, wherein the mixture of step (b) comprises PIC at a concentration sufficient to result in at least 4 log inactivation of the pathogen, if the pathogen is present.

20. The method of any one of claims 1-19, wherein the mixture of step (b) comprises PIC at a concentration of about 5 μM to about 500 μM.

21. The method of claim 20, wherein the mixture of step (b) comprises PIC at a concentration of about 145 μM to about 155 μM.

22. The method of claim 20, wherein the mixture of step (b) comprises PIC at a concentration of about 30 μM to about 90 μM.

23. The method of any one of claims 1-22, wherein the PAS comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

24. The method of any one of claims 1 to 23, further comprising, before step (c): (b1) incubating the mixture of step (b) for a period of 30 minutes to 24 hours.

25. The method of any one of claims 1-24, wherein the platelet composition comprises at least 2 x 10 11 Platelets.

26. The method of any one of claims 1-25, wherein the method is sufficient to inactivate at least 1 log of the pathogen, if the pathogen is present, and wherein the platelet composition after step (c) is suitable for transfusion into a subject without further processing to remove residual PIC or its photoproducts.

27. The method of any one of claims 1-26, wherein the method is sufficient to inactivate at least 1 log of the pathogen, if the pathogen is present, and wherein after step (c) the platelet composition is suitable for transfusion into a subject without transferring the platelet composition to a container comprising a compound adsorption device (CAD).

28. The method of any one of claims 1-27, wherein the method is sufficient to inactivate at least 1 log of the pathogen, if the pathogen is present, and wherein the platelet composition after step (c) comprises 5 μM or less of PIC.

29. The method of any one of claims 1-28, wherein the method is sufficient to inactivate at least 4 logs of the pathogen, if the pathogen is present, wherein the platelet composition after step (c) comprises 2 μM or less of PIC, and wherein the concentration of PIC in the mixture of the platelet preparation and the solution comprising PAS and PIC is about 15 μM to about 150 μM.

30. A method for preparing a platelet composition, comprising: (a) providing a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing the solution of step (a) with a platelet preparation; (c) incubating the mixture of the platelet preparation and the solution comprising PAS and PIC for a period of about 30 minutes to about 24 hours; and (d) subjecting the incubated mixture of step (c) to light sufficient to photochemically inactivate pathogens, if present, thereby producing a platelet composition wherein: (i) The method is sufficient to inactivate at least one log of the pathogen, if present; (ii) the concentration of PIC in the mixture of the platelet preparation and the solution comprising PAS and PIC is from about 15 μM to about 150 μM; and (iii) the platelet composition after subjecting the mixture of the platelet preparation and the solution comprising PAS and PIC to light comprises less than 5 μM PIC.

31. A kit for preparing a platelet composition, comprising: (a) a first container comprising a solution comprising a platelet additive solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing a platelet preparation mixed with a solution comprising PAS and PIC, The first container is not connected to the second container.

32. The kit of claim 31, wherein the first container is suitable for mixing the platelet preparation with a solution comprising PAS and PIC.

33. The kit of claim 31 or claim 32, wherein the second container is suitable for mixing the platelet preparation with a solution comprising PAS and PIC.

34. The kit of any one of claims 31-33, wherein the second container is suitable for subjecting the platelet preparation mixed with the solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

35. The kit of any one of claims 31-34, wherein the first container is suitable for subjecting the platelet preparation mixed with the solution comprising PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

36. The kit of any one of claims 31-35, wherein the second container comprises a compound adsorption device (CAD).

37. The kit of any one of claims 31-36, wherein the second container is suitable for storing a platelet composition.

38. The kit of any one of claims 31-37, further comprising a third container, wherein the third container comprises a compound adsorption device (CAD), and wherein the third container is connected to the second container.

39. The kit of any one of claims 31-38, further comprising at least one storage container, wherein the at least one storage container is suitable for storing a platelet composition, and wherein the at least one storage container is connected to the second container or to the third container, if the third container is present.

40. The kit of any one of claims 31-39, wherein the solution comprising PAS and PIC has a volume of about 100 mL to about 1000 mL.

41. The kit of any one of claims 31-40, wherein the PIC concentration is about 15 μM to about 1500 μM.

42. The kit of any one of claims 31-41, wherein the PIC is psoralen.

43. The kit of claim 42, wherein the PIC is amitosaline.

44. The kit of any one of claims 31-43, wherein the first container, the second container, or both the first container and the second container are adapted to be connected to an apheresis device or to a container comprising a platelet preparation.

45. A kit for preparing a platelet composition, comprising: (a) a first container comprising a platelet additive solution (PAS); (b) a second container comprising a pathogen inactivating compound (PIC); and (c) a third container suitable for containing a platelet preparation mixed with PAS and PIC, The first container and the second container are connected to each other, and neither the first container nor the second container is connected to the third container.

46. ​​The kit of claim 45, wherein the second container is suitable for combining the PAS and the PIC.

47. The kit of claim 45, wherein the first container is suitable for combining PAS and PIC.

48. The kit of any one of claims 45-47, wherein the second container is suitable for mixing the platelet preparation with PAS and PIC.

49. The kit of any one of claims 45-47, wherein the first container is suitable for mixing the platelet preparation with PAS and PIC.

50. The kit of any one of claims 45-47, wherein the third container is suitable for mixing the platelet preparation with PAS and PIC.

51. The kit of any one of claims 45-50, wherein the third container is suitable for subjecting the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

52. The kit of any one of claims 45-50, wherein the second container is suitable for subjecting the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

53. The kit of any one of claims 45-50, wherein the first container is suitable for subjecting the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate pathogens, if present.

54. The kit of any one of claims 45-53, wherein the third container comprises a compound adsorption device (CAD).

55. The kit of any one of claims 45-54, wherein the third container is suitable for storing a platelet composition.

56. The kit of any one of claims 45-55, further comprising a fourth container, wherein the fourth container comprises a compound adsorption device (CAD), and wherein the fourth container is connected to the third container.

57. The kit of any one of claims 45-56, further comprising at least one storage container, wherein the at least one storage container is suitable for storing a platelet composition, and wherein the at least one storage container is connected to the third container or to the fourth container, if the fourth container is present.

58. The kit of any one of claims 45-57, wherein the PIC is psoralen.

59. The kit of claim 58, wherein the PIC is amitosaline.

60. The kit of any one of claims 45-59, wherein the first container, the second container, or both the first container and the second container are adapted to be connected to an apheresis device or to a container comprising a platelet preparation.

61. A composition comprising a pathogen inactivating compound (PIC) and a platelet additive solution (PAS), wherein the composition is platelet-free.

62. The composition of claim 61, wherein the concentration of PIC is about 15 μM to about 1500 μM.

63. The composition of claim 61 or claim 62, wherein the PIC is psoralen.

64. The composition of claim 63, wherein the PIC is amitosaline.

65. The composition of any one of claims 61-64, wherein the PAS comprises one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

66. The composition of any one of claims 61-65, wherein the composition is sterile.

67. A platelet composition prepared by the method of any one of claims 1-30.

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