Blood bag system and process for the inactivation of pathogens in platelet concentrates by use of the blood bag system

Abstract

The present invention relates to a blood bag system, a method for its manufacture, and a process for reducing pathogens and leucocytes in biological fluids in particular in therapeutic quantities of platelet concentrates (PC) contained in the blood bag system, using UV-light and agitation, wherein part of the plasma of the PC is optionally exchanged against a platelet additive solution.

1 . A blood bag system comprising a biological fluid such as a platelet concentrate and further comprising:
 a storage bag ( 4 ) made from a plastic material,   an irradiation bag ( 2 ) made from a flexible plastic material substantially transparent to UV irradiation and having a volume capacity of at least 10 times of the volume of the biological fluid contained in the irradiation bag and,   the storage bag ( 4 ) and the irradiation bag ( 2 ) being one and the same bag or at least two different but interconnectable bags.   
   
   
       2 . The blood bag system according to  claim 1 , wherein the irradiation bag comprises one or more inlet tubes ( 1 ) and/or outlet tubes ( 3 ) and is provided with means for preventing the biological fluid contained in the irradiation bag ( 2 ) and to be treated to enter into and/or to access the inlet and/or outlet tubes to avoid dead areas formed inside the irradiation bag ( 2 ) in or around the tubes. 
   
   
       3 . The blood bag system according to  claim 1 , wherein the inlet tubes ( 1 ) and/or outlet tubes ( 3 ) comprise at least one clamp-off part, plug ( 18 ) or break-off part ( 15 ) as a closing for the tube end extending into the irradiation bag, preferably located at the inner end of the tube, in particular the outlet tube ( 3 ), in which case the closing is openable. 
   
   
       4 . The blood bag system according to  claim 1 , wherein the irradiation bag ( 2 ) comprises a sealing ( 17 ) providing a compartment containing the biological fluid to be treated and a compartment separated therefrom comprising the inner end(s) of the one or more inlet tubes ( 1 ) and/or outlet tubes ( 3 ), the sealing preferably being located at one corner of the bag. 
   
   
       5 . The blood bag system according to  claim 4 , wherein the separated compartment comprises one or more inlet tubes only. 
   
   
       6 . The blood bag system according to  claim 1 , wherein the biological fluid contained in the irradiation bag does not contain a photosensitizer having an absorption maximum in the range of 200 to 270 nm, in particular 200 to 350 nm, and preferably is free of any pathogen inactivating substance added to the biological fluid and free of any photosensitizer. 
   
   
       7 . The blood bag system according to  claim 1 , wherein the biological fluid is a suspended platelet concentrate comprising plasma wherein at least 20 weight % of the plasma contained in the platelet concentrate is exchanged against a platelet storage solution to form a suspended platelet concentrate and the platelet storage solution comprises water and soluble salts. 
   
   
       8 . The blood bag system according to  claim 7 , wherein the greater 50 weight %, preferably greater 70 weight %, of the plasma is exchanged against a platelet storage solution. 
   
   
       9 . The blood bag system according to  claim 7 , wherein the platelet storage solution contains at least one of the following salts: citrate, phosphate and/or acetate. 
   
   
       10 . The blood bag system according to  claim 1 , wherein the biological fluid comprises 0.2 to 2.5×10 9  platelets per ml biological fluid contained in the blood bag system. 
   
   
       11 . The blood bag system according to  claim 1 , wherein
 the irradiation bag ( 2 ) is different from the storage bag ( 4 ), wherein the storage bag ( 4 ) has optionally half or less of the volume capacity of the irradiation bag ( 2 ) and   the blood bag system comprises a tubing ( 3 ) for interconnecting the irradiation bag ( 2 ) and the storage bag ( 4 ), optionally detachable.   
   
   
       12 . The blood bag system according to  claim 11 , wherein the storage bag ( 4 ) has 20% or less of the volume capacity of the irradiation bag ( 2 ). 
   
   
       13 . The blood bag system according to  claim 11 , wherein the irradiation bag ( 2 ) and the storage bag ( 4 ) consist of the same plastic material. 
   
   
       14 . The blood bag system according to  claim 11 , wherein the irradiation bag ( 2 ) and the storage bag ( 4 ) consist of different plastic materials. 
   
   
       15 . The blood bag system according to  claim 1 , wherein at least the irradiation bag ( 2 ) consists of EVA. 
   
   
       16 . The blood bag system according to  claim 1 , wherein the storage bag ( 4 ) is permeable for at least one gas, selected from the group consisting of air, oxygen and carbon dioxide. 
   
   
       17 . The blood bag system according to  claim 1 , wherein the irradiation bag ( 2 ) is made from material that has no adsorption maximum in the range of 200 to 350 nm, preferably 250 to 300 nm. 
   
   
       18 . The blood bag system according to  claim 1 , wherein the irradiation bag ( 2 ) has a flat inside, the inside having boundaries when viewed from the top that have at least 4, preferably 6 or 8 corners or form a circle or oval when filled with the biological fluid. 
   
   
       19 . The blood bag system according to  claim 1 , further comprising a leucocyte filter ( 8 ) optionally as part of the inlet tube ( 3 ) for the irradiation bag ( 2 ). 
   
   
       20 . A method for manufacturing a blood bag system according to  claim 1 , comprising the following steps:
 providing an irradiation bag ( 2 ) made from a flexible plastic material substantially transparent to UV irradiation and comprising at least one inlet tube ( 1 ) preferably located at one corner of the bag ( 2 ),   introducing the biological fluid into the irradiation bag ( 2 ) via the inlet tube so that the irradiation bag ( 2 ) is less then 20 vol % filled, preferably filled from less than 10 vol % to 1 vol %,   sealing the bag thereby creating a first sealed compartment into which the inlet tube ( 1 ) opens and a second sealed compartment comprising the biological fluid.   
   
   
       21 . A process for the inactivation of pathogens and the reduction of leucocytes in platelet concentrates in a blood bag system according to  claim 1 , comprising the following steps:
 obtaining a platelet concentrate from human blood donation by apheresis techniques or by buffy-coat pooling techniques,   inserting the platelet concentrate into the irradiation bag ( 2 ) so that the irradiation bag is less then 20 vol % filled, preferably filled from 10 to 1 vol %,   irradiating the irradiation bag comprising platelet concentrate with an irradiation source comprising UV-C light of a wavelength of 200 to 270 nm while keeping the irradiation bag under agitation and   inserting the irradiated platelet concentrate into the storage bag ( 4 ) for storage or remaining the irradiated platelet concentrate in the irradiation bag for storage in the irradiation bag.   
   
   
       22 . A process according to  claim 21 , comprising the following further step
 exchanging at least 20 weight %, preferably at least 50 weight %, of the plasma contained in the platelet concentrate against a platelet storage solution to form a suspended platelet concentrate, the platelet storage solution comprises water and one or more soluble salts before exposing the platelet concentrate to UV irradiation.   
   
   
       23 . The process according to  claim 21 , wherein the UV-irradiation is generated by a quartz lamp, a LED- and/or flash-light lamp. 
   
   
       24 . The process according to  claim 21 , wherein the irradiation bag is placed upon a stiff sheet, optionally made from glass/quartz material, while irradiated and agitated. 
   
   
       25 . The process according to  claim 21 , wherein the filled irradiation bag has an average thickness of less than 5 mm, preferably less than 2.5 mm, when irradiated. 
   
   
       26 . The process according to  claim 21 , wherein the irradiation bag is agitated to homogeneously mix the fluid content and/or to obtain a fluid profile with wave like surface areas in the irradiation bag comprising a multiplicity of moving or standing troughs and crests, wherein the troughs at their lowest spot preferably have average film thickness of less than 2.5 mm. 
   
   
       27 . The process according to  claim 21 , wherein the light dose for irradiation of the irradiation bag is between 0.01 and 2 J/cm 2 . 
   
   
       28 . The process according to  claim 21 , wherein the platelet concentrate/suspended platelet concentrate is stored at room temperature, preferably for at least 8 days. 
   
   
       29 . The process according to  claim 21 , wherein the stored platelet concentrates/suspended platelet concentrates are stored at room temperature under slight agitation, preferably for at least 8 days. 
   
   
       30 . The process according to  claim 21 , wherein the irradiation bag is agitated while irradiated by means of a steady agitation using an amplitude of from 0.2 to 8 cm in the x and the y direction of the plane, wherein x and y are preferably the same, and a frequency of the amplitude from 10 to 200 Hz. 
   
   
       31 . The process according to  claim 21 , wherein the platelet concentrate contained in the irradiation bag does not contain a photosensitizer having an absorption maximum in the range of in particular 200 to 350 nm, more particularly 200 to 270 nm, and preferably if free of any pathogen inactivating substance added to the biological fluid or any photosensitizer. 
   
   
       32 . The process according to  claim 31 , wherein the irradiation bag is irradiated and agitated while stretched out flat and horizontal on a substantially plane sheet without any clamping of the upper layer of the irradiation bag thus allowing the upper layer to freely move in reaction to the agitation of the bag.