Bag system for the treatment of a biological fluid by electromagnetic irradiation

Abstract

The invention relates to a bag system (1) for treating a biological fluid by electromagnetic irradiation. The bag system comprises at least one element consisting of an irradiation bag (2) intended to contain the biological fluid to be irradiated. The irradiation bag (2) is made of a material permeable to the electromagnetic radiation. The bag system (1) further comprises at least one protective film (26a, 26b) covering the irradiation bag (2). The protective film (26a, 26b) is made of a gas barrier polymeric material with an oxygen permeability less than or equal to 100 cm3 / m2 / 24 at a temperature of 23 °C and a relative humidity of 50%.

Description

[0001] The invention relates to a pouch system for the treatment of a biological fluid by electromagnetic irradiation, as well as an assembly comprising said pouch system and packaging.

[0002] It applies to the medical and biomedical field, in particular to the field of blood transfusion and even more specifically to the field of blood processing.

[0003] In the context of transfusion, blood is first collected from a donor and then separated by centrifugation into different blood products such as red blood cell concentrates, plasma, and platelet concentrates. To improve the quality and safety of these different blood products, they may undergo various treatments such as the removal of leukocytes and / or the reduction of pathogens.

[0004] Document WO 2007 / 076834 describes a process for reducing pathogens such as bacteria, viruses, and / or leukocytes from platelet concentrates. In this process, a bag containing a platelet concentrate is irradiated with UV radiation under agitation. This process has the advantage over other pathogen inactivation processes, such as the commercial processes Intercept (Cerus) and Mirasol (TerumoBCT), of not using a photosensitive agent such as amotosalen or riboflavin.

[0005] In these light-based processes, and especially in the absence of a photosensitive agent, it is important to ensure that the blood product to be treated receives the necessary and sufficient dose to reduce the level of pathogens to an acceptable level, without deteriorating the biological properties of the blood product.

[0006] Document WO 2008 / 034476 describes a pouch system adapted for implementing the UV radiation pathogen reduction process described in document WO 2007 / 076834. The pouch system essentially comprises an irradiation pouch made of ethylene-vinyl acetate copolymer (EVA) connected to a platelet concentrate storage pouch made of plasticized polyvinyl chloride (PVC). The pouch system also includes tubing made of plasticized PVC.

[0007] This document states that the absorption of UV light by EVA is influenced by the degree of polymerization and crosslinking of the EVA.

[0008] Other intrinsic factors influence the UV transmittance of an EVA sheet, such as the relative proportion of ethylene and vinyl acetate repeats, the film thickness, and its surface condition. Extrinsic factors impacting UV transmittance include heat, humidity, the presence of oxygen, and exposure to UV radiation.

[0009] After extensive research, the applicant identified another previously undescribed factor impacting the UV transmittance of an EVA sheet.

[0010] The applicant has indeed highlighted that the UV transmittance of an EVA pouch deteriorates due to the migration of certain plasticizers from the PVC of other elements of the pouch system as well as the migration of certain substances from the packaging in which the pouch system is confined.

[0011] Indeed, pocket systems such as the one described in document WO 2008 / 034476 include elements such as connectors or tubing, made of PVC plasticized with di-2-ethylhexyl phthalate (DEHP, di-2-ethylhexyl phthalate).

[0012] DEHP is also known to be an endocrine disruptor with potential effects on the reproductive, hormonal, and immune systems. It is also a potential carcinogen. Therefore, it is recommended to eliminate DEHP from medical devices such as blood collection bag systems.

[0013] DEHP-free bag systems for blood processing are known. For example, document JP2003-171288A describes a bag system comprising a filter for removing leukocytes from whole blood and a plurality of bags for containing blood components, connected to said filter. At least one of the bags contains a citrate-type plasticizer, the other bags being made of PVC plasticized with a citrate ester or a trimellitate ester.

[0014] Document EP 2 731 425 B1 describes a phthalate-free plasticizer-free bag for storing red blood cell products. The bag is made of a polymer material plasticized with diisononyl ester of 1,2-cyclohexanedicarboxylic acid (DINCH) and contains a specific additive solution.

[0015] The PVC bag systems in these two documents are not suitable for electromagnetic irradiation of blood components and the choice of plasticizer is motivated by the reduction of hemolysis of red blood cells in DEHP-free bags.

[0016] Rather than removing DEHP from medical devices, document FR 2965812 proposes to eliminate the migration of DEHP or other plasticizing compound from a plasticized PVC object such as tubing, by coating the object with a layer of metal oxide such as titanium dioxide.

[0017] Furthermore, document EP 1 972 354 describes a pouch system for the separation and reduction of pathogens from a biological fluid using a photosensitive agent activated by ultraviolet radiation, in which the pouch(es) containing the photosensitive agent are arranged in a removable opaque overwrap. This overwrap prevents premature activation of the photosensitive agent by ambient light.

[0018] Finally, US patent 2019 / 0230919 describes kits for reducing the oxygen level in blood or blood components to improve their preservation. These kits essentially consist of a sealed, oxygen-impermeable outer container; a flexible inner bag for receiving the blood or blood components; and an oxygen absorber placed inside the outer container. The inner bag is made of an oxygen-permeable material such as polyvinylidene fluoride, silicone, or polyurethane. WO patent 2021 / 231650 describes similar kits in which the inner bag is made of polyvinyl chloride plasticized with di-2-ethylhexyl phthalate (DEHP), diisononyl ester of 1,2-cyclohexanedicarboxylic acid (DINCH), or butyryl trihexyl citrate (BTHC).Because of the closed external container enclosing the internal pouch, these kits are not suitable for the treatment of blood or blood components by electromagnetic irradiation.

[0019] In order to preserve the transmittance of an irradiation pocket of a pocket system, the invention proposes, according to a first aspect, a pocket system for the electromagnetic irradiation treatment of a biological fluid, said pocket system comprising at least one element consisting of an irradiation pocket intended to contain the biological fluid to be irradiated, said irradiation pocket being made of a material permeable to said electromagnetic radiation, said system comprising one or more other elements chosen from the group consisting of at least one storage pocket and a tube, at least one of said other elements being made of a polymer material formulated with a plasticizer and at least one protective film forming a medium barrier to the plasticizer and covering said irradiation pocket,said protective film being made of a gas barrier polymer material having an oxygen permeability less than or equal to 100 cm³ / m² / 24h at a temperature of 23°C and a relative humidity of 50%.

[0020] According to a second aspect, the invention relates to an assembly for the treatment by electromagnetic irradiation of a biological fluid comprising a package and a bag system according to the first aspect of the invention, said bag system being confined in a sterile manner in said package.

[0021] According to a third aspect, the invention relates to the use of a film made of a gas barrier polymer material having an oxygen permeability less than or equal to 100 cm 3< / m 2< / 24 h at a temperature of 23°C and a relative humidity of 50% as a barrier means to the releasable plasticizers of polyvinyl chloride.

[0022] Other items and benefits will appear in the description that follows. [ Fig.1 [ ] represents a schematic view of an assembly according to an embodiment of the invention comprising a sterile package in which is arranged a pouch system for the UV irradiation of a blood product. Fig. 2 ] represents the UV transmittance rate of a sheet made of EVA between 0 and 1200 days, below which is placed another sheet made of EVA and above which are superimposed one or two sheets made of PVC laminated by DEHP, DEHT, TOTM or DINCH (side A). Fig.3 ] represents the UV transmittance rate of a sheet made of EVA between 0 and 1200 days, on top of which are superimposed another sheet made of EVA and one or two sheets made of PVC plasticized by DEHP, DEHT, TOTM or DINCH (side B).

[0023] The invention relates to a pocket system and an assembly for the treatment of a biological fluid by electromagnetic irradiation.

[0024] Biological fluid includes whole blood or a blood product obtained by filtration and / or centrifugation of whole blood such as plasma, platelet-rich plasma, red blood cell concentrate or platelet concentrate.

[0025] In order to reduce pathogens such as viruses, bacteria and / or leukocytes in the blood or blood product, it is known to apply electromagnetic radiation to the blood or blood product, with or without a photosensitive agent.

[0026] Electromagnetic radiation refers to non-ionizing radiation with wavelengths ranging from 10 nm to 10 µm, that is, visible, ultraviolet (UV), and / or infrared radiation. Specifically, electromagnetic radiation includes visible radiation with wavelengths ranging from 340 nm to 800 nm and / or UV radiation with wavelengths ranging from 200 to 340 nm. More precisely, UV-C radiation has wavelengths ranging from 200 to 280 nm. Even more specifically, UV-C radiation has a wavelength of approximately 254 nm.

[0027] According to the [ Fig.1 ], the set 20 for magnetic irradiation treatment comprises a package 21 and a bag system 1 sterilely contained in said package 21.

[0028] The packaging 21 is suitable for allowing the sterilization of the bag system 1 in which it is confined.

[0029] In one implementation, the packaging is packaging suitable for sterilization by gases, such as ethylene oxide.

[0030] According to one embodiment, the packaging is made of one or more materials formulated without phthalates or terephthalates. For example, packaging 21 is formed by assembling a porous non-woven sheet and a transparent film sheet. The porous sheet allows the sterilizing gas to pass into the packaging while preventing microbes from entering it. The porous sheet is made, for example, of cellulose non-woven material such as paper or of synthetic non-woven material such as high-density polyethylene fibers (Tyvek®). The transparent film sheet is made, for example, of transparent polymer such as high-density polyethylene, low-density polyethylene, polypropylene, and / or polyester. The porous non-woven sheet and the transparent film sheet are joined, for example, by welding.

[0031] According to the [ Fig.1 The pocket system for the electromagnetic irradiation of a biological fluid comprises at least one element consisting of an irradiation pocket 2 intended to contain the biological fluid to be irradiated. The irradiation pocket is made of a material permeable to said electromagnetic radiation.

[0032] According to one embodiment, irradiation by electromagnetic radiation is irradiation by UV radiation, in particular UV-C radiation, and the irradiation pocket is made of a material permeable to UV radiation, in particular UV-C radiation.

[0033] The biological fluid to be treated is in particular blood or a blood product such as a platelet concentrate.

[0034] For example, irradiation pocket 2 is made of EVA. Alternatively, irradiation pocket 2 is made of a UV-permeable polymer material such as polymethylpentene, polychlorotrifluoroethylene, perfluoroalkoxy, fluorinated ethylene propylene, ethylene tetrafluoroethylene, ethylene chlorotrifluoroethylene, or polyvinylidene fluoride. The irradiation pocket material is formulated without phthalates or terephthalates.

[0035] Phthalate or terephthalate refers to a derivative of phthalic or terephthalic acid, such as an ester of phthalic or terephthalic acid.

[0036] A phthalate- and terephthalate-free formulated material is a material in which no phthalate or terephthalate has been added as a plasticizer in the material composition.

[0037] Phthalate-free or terephthalate-free material may contain residual traces of phthalate or terephthalate, i.e. a content of less than 1000 ppm, linked for example to contamination during the manufacturing process of the material or the bag system or during its packaging.

[0038] In particular, the irradiation pocket 2 is formed from a sheath or by assembling two sheets permeable to UV radiation, the sheath or each sheet having a UV-C transmittance greater than 60%, in particular greater than 65%. Even more particularly, the UV-C transmittance of the sheath or each of the sheets is less than 90%, in particular less than 85%.

[0039] UV transmittance refers to the ratio, expressed as a percentage, of the transmitted radiation intensity to the incident radiation intensity. Transmittance is determined by spectrophotometry.

[0040] According to a particular embodiment, the irradiation pocket 2 is free of photosensitive agent. In other words, the irradiation pocket 2 does not contain a photosensitive agent such as riboflavin, a psoralen derivative, or a phenothiazine derivative.

[0041] According to the [ Fig.1 ], the irradiation pocket 2 includes a first access port 3 in fluidic communication with the internal volume 4 of the irradiation pocket 2. The irradiation pocket 2 further includes a second access port 5 in fluidic communication with the internal volume 4 of the irradiation pocket 2.

[0042] The irradiation bag 2 is in fluidic communication with a first tube 6 via the first access port 3. The first tube 6 is provided at its end with two vents 7a, 7b, each comprising a filter membrane that allows air to pass through and forms a sterile barrier. These vents allow for gas sterilization of the bag system 1.

[0043] The irradiation pocket 2 further includes openings 19a, 19b, 19c, 19d, 19e made in one or more peripheral edges of the irradiation pocket 2 allowing the suspension and / or maintenance of said irradiation pocket 2.

[0044] The bag system 1 further includes a storage bag 8 for collecting and storing the treated blood component. This storage bag 8 is in fluidic communication with the irradiation bag 2 via the second tube 9, which is connected at one end to a second access port 5 of the irradiation bag 2 and at the other end to an access port 10 of the storage bag 8. The storage bag 8 further includes two outlet ports 22, 23, each closed by a breakable cap 24, 25 with fins.

[0045] A removable plug 27 is disposed in the second access port 5 of the irradiation bag 2, closing the fluidic communication between the internal volume 4 of the irradiation bag 2 and the second tube 9 leading to the storage bag 8. The removable plug 27 can slide out of the second access port 5, into the internal volume 4 of the container 2 in order to allow fluidic communication between the irradiation bag 2 and the storage bag 8.

[0046] The bag system 1 further includes a sampling bag 11 in fluidic communication with the storage bag 8 via a third tube 12 connected at one end to a second access port 13 of the storage bag 8 and at its other end to an access port 14 of the sampling bag 11.

[0047] A fourth tube 15 is connected at one of its ends to the third tube 12 via a three-way connector 16. The other end of this fourth tube 15 is provided with two vents 17a, 17b each comprising a filter membrane allowing air to pass through and forming a sterile barrier.

[0048] Each of the tubes 6,9,12,15 is equipped with a clamp 18a,18b,18c,18d which allows the selective control of opening and closing the flow of liquids in each of these tubes.

[0049] The pocket system 1 advantageously includes at least one protective film 26a covering the irradiation pocket. The protective film is a very thin sheet of plastic material. It is made of a polymer material formulated without phthalates or terephthalates. The protective film 26a is placed over the irradiation pocket, completely covering its surface. The protective film 26a is, for example, positioned between the irradiation pocket 2 and the porous sheet, in particular made of lacquered paper, of the packaging 21.

[0050] The protective film serves to protect the irradiation pocket 2 from substances that could impair its transmittance, particularly its UV transmittance, and even more specifically its UV-C transmittance. The irradiation pocket 2 is uncovered by this protective film at the moment of its treatment with electromagnetic radiation.

[0051] This protective film thus forms a barrier against leachable substances from other components of the bag system, which impair the transmittance of the irradiation bag. A leachable substance is defined as a substance that migrates from a component of the bag system or its packaging. Examples of leachable substances include PVC plasticizers such as phthalates or terephthalates, cyclohexanedicarboxylic acid esters, or citrate esters. In other words, the protective film forms a barrier against the plasticizer of a polymer material such as PVC.

[0052] Indeed, in its packaging 21, the pocket system 1 is folded so as to place the storage pocket 8 on the irradiation pocket 2. In this configuration, without protective film, the leachable plasticizers of the pocket system migrate towards the irradiation pocket 2. The presence of these leachable substances on the irradiation pocket deteriorates its optical properties, in particular its UV transmittance, and even more particularly its UV-C transmittance.

[0053] This protective film also shields the irradiation bag from substances in the environment that could impair its transmittance. Phthalates, particularly DEHP, are ubiquitous and potential sources of contamination for the irradiation bag.

[0054] According to one embodiment, a protective film made of a gas-barrier polymer material having an oxygen permeability less than or equal to 100 cm³ / m² / 24 h at a temperature of 23°C and a relative humidity of 50% is used as a barrier medium against leachable plasticizers from polyvinyl chloride, such as DEHP or DEHT. In particular, the protective film material is also a water vapor barrier polymer material having a water vapor permeability less than or equal to 10 g / m² / 24 h at a temperature of 23°C and a relative humidity of 50%.

[0055] Thus, the protective film 26a is made of a gas barrier polymer material having an oxygen permeability less than or equal to 100 cm³ / m² / 24 h, more specifically less than or equal to 90, at a temperature of 23°C and a relative humidity of 50%. The oxygen permeability is measured in accordance with ASTM D 3985.

[0056] In particular, the polymer material of the protective film 26a is a water vapor barrier polymer material having a water vapor permeability less than or equal to 10 g / m² / 24 h, more specifically less than 5 g / m² / 24 h at a temperature of 23°C and a relative humidity of 50%. The water vapor permeability is measured in accordance with ASTM F 1249.

[0057] In particular, the protective film comprises at least one layer made of polyester or polypropylene. For example, the protective film comprises a composite multilayer sheet with one layer made of polyester and one layer made of polypropylene. Alternatively, the protective film comprises a composite multilayer sheet with two layers made of polyester or two layers made of polypropylene.

[0058] Advantageously, the protective film is transparent, allowing the user to see the irradiation pocket 2.

[0059] The thickness of the protective film is between 40 and 70 µm, in particular between 45 and 65 µm.

[0060] In one embodiment, the pocket system comprises two protective films 26a, 26b arranged on either side of the irradiation pocket 2. The irradiation pocket 2 is thus sandwiched between the two protective films 26a, 26b until it is treated with electromagnetic radiation. Alternatively, the protective film is folded over itself to form a sheet in which the irradiation pocket 2 is sandwiched.

[0061] According to another embodiment, the two protective films 26a, 26b together form a sleeve having at least one open end. The open end of the sleeve allows the user to easily slide the sleeve off the irradiation bag 2 just before processing the biological fluid contained in the irradiation bag. The irradiation bag 2 is placed inside this sleeve so as to enclose it. The sleeve surrounds the irradiation bag 2 to protect it from the migration of plasticizers or other leachable substances that could impair the transmittance of the irradiation bag 2.

[0062] For example, the sleeve is made by superimposing the two protective films 26a,26b, and welding together two opposite sides and one transverse side.

[0063] In this embodiment, the irradiation bag 2 is protected from the leachable substances from the bag system 1 and the packaging 21.

[0064] In order to ensure the preservation of the optical properties of the irradiation pocket 2 of the pocket system 1, in addition to the irradiation pocket 2, the other element(s) of the pocket system are made of one or more materials formulated without phthalate or terephthalate.

[0065] According to one embodiment, each of said other elements is made of one or more materials chosen from the group consisting of a material other than plasticized polyvinyl chloride and a polymer material formulated with at least one plasticizer other than a phthalate such as di-2-ethylhexyl phthalate or a terephthalate such as di-2-ethylhexyl terephthalate.

[0066] Indeed, it has been identified by the applicant that phthalate and terephthalate esters such as di-2-ethylhexyl phthalate (DEHP) or di-2-ethylhexyl terephthalate (DEHT) which migrate towards irradiation pocket 2 lower the UV transmittance, more particularly the UV-C transmittance, of irradiation pocket 2.

[0067] Thus, each of the other elements of the pocket system 1 is advantageously made of one or more materials other than polyvinyl chloride plasticized by di-2-ethylhexyl phthalate or di-2-ethylhexyl terephthalate.

[0068] Advantageously and for the same reasons, the packaging in which the pouch system is confined is made of one or more materials formulated without phthalate or terephthalate, in particular without di-2-ethylhexyl phthalate (DEHP) or di-2-ethylhexyl terephthalate (DEHT).

[0069] In a particular embodiment, each of the other elements of the pocket system is made either of polyvinyl chloride plasticized by a plasticizer selected from the group consisting of a cyclohexanedicarboxylic acid ester, a citrate ester, a trimellitate ester or a mixture thereof, or of a material other than plasticized polyvinyl chloride.

[0070] More specifically, each of the other elements of the pocket system is made either of polyvinyl chloride plasticized by a plasticizer selected from the group consisting of 1,2-cyclohexanedicarboxylic acid diisononyl, trihexyl butyl citrate, tri-2-ethylhexyl trimellitate or a mixture thereof, or of a material other than plasticized polyvinyl chloride.

[0071] The other elements of the pocket system include one or more elements selected from the group consisting of a storage pocket 8, a sampling pocket 11, a tubing 6,9,12,15, a connector 16, a clamp 18a,18b, 18c, 18d, a vent 7a, 7b, 17a, 17b and their combinations.

[0072] The rigid elements of the pocket system, for example the clips and vents, are made of a material other than plasticized polyvinyl chloride, such as polycarbonate, polyester, polyethylene and / or polypropylene.

[0073] For example, clamps 18a, 18b, 18c, 18d are made of polycarbonate. Vents 7a, 7b, 17a, 17b are made of polypropylene.

[0074] The flexible elements of the pocket system, other than the irradiation pocket 2, are made of polyvinyl chloride plasticized by at least one plasticizer selected from the group consisting of a cyclohexanedicarboxylic acid ester, a citrate ester, a trimellitate ester and a mixture thereof.

[0075] The storage bag 8 is made of a gas-permeable material to allow the storage of a platelet concentrate for at least 3 to 7 days. For example, the storage bag 8 is made of PVC plasticized with tris(ethylhexyl) trimellitate (or tri-octyl trimellitate, TOTM) or trihexyl butyl citrate (BTHC).

[0076] For example, sampling bag 11 is made of PVC plasticized with diisononyl ester of 1,2-cyclohexanedicarboxylic acid (DINCH).

[0077] For example, tubes 6, 9, 12, 15 and connector 16 are made of PVC plasticized by DINCH.

[0078] The components of the irradiation 2, storage 8 and sampling 11 pockets such as the access ports 3,5,10,13,14, the outlet ports 22,23 and the plugs 24,25,27 are also advantageously made of one or more materials formulated without phthalate or terephthalate.

[0079] In connection with the completion of set 20 of the [ Fig.1 ], we now describe a process for implementing the pocket system 1 and its packaging 21.

[0080] The packaging 21 in which the pocket system 1 is contained is opened before removing the pocket system 1.

[0081] A source bag (not shown) containing a biological fluid, for example a platelet concentrate from apheresis or a mixture of platelet concentrates obtained from leukocyte-platelet layers, is sterilely connected to the bag system 1 via the first tubing 6, using a sterile TSCD-II type connection device (Terumo).

[0082] The biological fluid from the source pocket is then transferred by gravity into the internal volume 4 of the irradiation pocket 2 through the first access port 3.

[0083] After the transfer, the air contained in the internal volume 4 of the irradiation pouch 2 is expelled from the irradiation pouch 2 through the first access port 3 by applying pressure to the irradiation pouch. Once the air has been expelled, the first access port 3 is closed by welding.

[0084] These air purging and welding operations are advantageously carried out using the welding device described in document WO2022 / 029040.

[0085] The first tube 6 is welded and cut in order to separate the source bag initially containing the biological fluid, from the bag system 1.

[0086] Next, the irradiation pocket 2 is removed from the sleeve formed by the two sheets 26a,26b. Alternatively, this sleeve is removed from the irradiation pocket 2 at any other time before the irradiation operation.

[0087] Irradiation bag 2 is irradiated under agitation with UV light in order to inactivate any pathogens present in the biological fluid.

[0088] The removable cap 27 closing the second access port 5 is pushed inside the irradiation bag 2, then the irradiated biological fluid is transferred into the storage bag 8 to be stored for up to 5 to 7 days.

[0089] After the transfer, the second tube 9 is welded and cut using a hand welder in order to separate container 2 from the rest of the bag system 1.

[0090] In one embodiment, a sample of the biological fluid is sent into the sampling bag 11 for analysis. It is separated from the storage bag 8 by welding and cutting the third tube 12, using a hand welder. Examples Example 1: Impact of the packaging and various PVC-coated components of the pocket system on the UV transmittance of an EVA sleeve

[0091] Six test configurations were carried out and analyzed: EVA sheath (control); EVA sheath packaged in a bag made of two transparent composite films of polyester (PET) and polyethylene (PE); EVA sheath packaged in a bag made of two sheets of lacquered paper; BTHC-plasticized PVC storage pouch placed on the EVA sheath, and DEHP-plasticized PVC sampling pouch placed over the storage pouch and the EVA sheath, all packaged in a bag made of a transparent composite film of PET and PE and a sheet of lacquered paper; EVA sheath protected by a composite polymer sleeve of PET and polypropylene (PP), a TOTM-plasticized PVC storage pouch placed on the protected EVA sheath, and a DEHP-plasticized PVC sampling pouch placed over the storage pouch and the protected EVA sheath, all packaged in a bag made of a transparent composite film of PET and PE and a sheet of lacquered paper.BTHC-plasticized PVC storage pouch placed on the EVA sleeve, and DEHP-plasticized PVC sampling pouch placed across the storage pouch and the EVA sleeve, all packaged in a bag made of a transparent composite film of bi-oriented PET and polypropylene (PP) and a paper sheet.

[0092] The EVA sheath has substantially the dimensions of an irradiation bag.

[0093] The sleeve made of PET and PP composite polymer has a thickness of approximately 55 µm, an oxygen permeability of less than 91.0 cm3 / m 2< / 24h h at a temperature of 23 °C and a relative humidity of 50% and a water vapor permeability of less than 5.0 cm 3< / m 2< / 24h h at a temperature of 23 °C and a relative humidity of 50%.

[0094] Transmittance measurements are performed using a spectrophotometer (Perkin Elmer Lamdbda650). [Table 1] UV-C transmittance (%) Average (%) T 0 Average (%) T 1 month Average (%) T 3 months EVA sheath 64,61 65,09 63,76 EVA sheath 64,61 54,90 52,70 PET / PE bag EVA sheath 64,61 59,98 56,95 lacquered paper bag EVA sheath 64,61 61,08 57,17 PVC / DEHP bag PVC / BTHC bag PET / PP bag and lacquered paper EVA sheath 64,61 65,17 64,02 PET / PP sleeve PVC / DEHP bag PVC / BTHC bag PET / PP bag and lacquered paper EVA sheath 64,61 63,75 63,22 PVC / DEHP bag PVC / BTHC bag biooriented PET / PP bag and paper

[0095] These results demonstrate the negative impact of a particular packaging bag, both the transparent film and the lacquered paper sheet, on the UV transmittance of the irradiation pouch. This impact is amplified by the presence of other components of the plasticized PVC pouch system.

[0096] The presence of the protective sleeve ensures that the EVA irradiation pouch is not contaminated by PVC plasticizers or other leachable substances from the packaging, thus maintaining UV transmittance. Example 2: Impact of plasticizer migration from a PVC sheet on the UV transmittance of an EVA sheet.

[0097] Six test configurations were carried out by superimposing rectangular samples of approximately 60 cm² of sheets of different materials: two samples of EVA sheet; two samples of EVA sheet and two samples of PVC sheet plasticized by DEHP; two samples of EVA sheet and two samples of PVC sheet plasticized by BTHC; two samples of EVA sheet and one sample of PVC sheet plasticized by DEHT; two samples of EVA sheet and one sample of PVC sheet plasticized by TOTM; two samples of EVA sheet and one sample of PVC sheet plasticized by DINCH.

[0098] The EVA sheet in direct contact with the sample of plasticized PVC sheet is identified as "side A", the EVA sheet placed under side A is identified as "side B".

[0099] The UV transmittance of EVA sheets was determined at different times between 0 and 3 years. The results are shown on the... figures 2 and 3 . 2.1 Impact of DEHP

[0100] A sharp drop in UV transmittance is observed in the EVA sheet in direct contact with a sample of DEHP-coated PVC sheet (side A). By the 14th day of contact, the transmittance of the EVA sheet is less than 60%. After two years, the UV transmittance of the EVA sheet is less than 10%.

[0101] On side B, the transmittance loss becomes less than 60% after 100 days.

[0102] The EVA sheet slows down but does not prevent the migration of DEHP. 2.2 Impact of BTHC and DINCH

[0103] Under the conditions of the study, contact of the EVA sheet (side A and B) with a sample of PVC sheet plasticized by BTHC or DINCH has no influence on the transmittance of the EVA sheet throughout the 3 years. 2.3 Impact of DEHT

[0104] Direct contact of the DEHT-plasticized PVC sheet sample with the EVA sheet (side A) causes an even greater loss of UV transmittance in the EVA sheet than with the DEHP-plasticized PVC sheet.

[0105] The impact of the DEHT-coated PVC sheet is less pronounced on side B, due to the presence of side A which slows down the migration of DEHT. 2.4 Impact of TOTM

[0106] A decrease in UV transmittance was observed on the EVA sheet (side A) in direct contact with a sample of TOTM-coated PVC sheet. TOTM is known for its minimal migration within a PVC matrix but absorbs UV radiation, particularly UVC. However, this result should be interpreted with caution as it represents the average of three tests: two tests showed a UV transmittance of 55-57% on the EVA side at the end of the study, and one test showed a transmittance of less than 2%. The results for side B were also inconsistent.

[0107] These studies show that DEHT should be avoided in the same way as DEHP in bag systems intended to treat a biological fluid by UV irradiation. Example 3: Impact of PVC plasticizer migration in tubing on the UV transmittance of an EVA sheet.

[0108] Three test configurations were carried out with a rectangular sample of EVA sheath measuring 15 cm x 18 cm alone or by layering it with 60 cm of tubing of different materials, all packaged in a bag made of a transparent composite film of bi-oriented PET and polypropylene and a paper sheet: an EVA sheath sample (control); an EVA sheath sample and a DINCH plasticized PVC tubing sample; an EVA sheath sample and a TOTM plasticized PVC tubing sample.

[0109] As with DINCH-plasticized PVC sheet, contact of DINCH-plasticized PVC tubing with an EVA sheath has no influence on the UV transmittance of the EVA sheath.

[0110] Contact between a PVC tube coated with TOTM and an EVA sheath results in a decrease of approximately 5% in the UV transmittance of the EVA sheath after 90 days. This decrease reaches more than 10% after one year. Example 4: Ability of different materials to protect the UV transmittance of the EVA irradiation pouch

[0111] A single packaging bag made of a transparent composite film of PET and PE and a lacquered paper sheet is sealed to form two separate compartments. Each compartment contains a sample of EVA tubing (15 cm x 15 cm) protected by an open sleeve. In addition, two samples of DEHP-coated PVC (15 cm x 15 cm) are inserted between the bag and the EVA tubing protected by the sleeve in the upper compartment.

[0112] Different materials are being tested to make the protective sleeve: PET copolymer film, PET and PP copolymer film or spun-bonded non-woven PET film. [Tableaux2] UV-C transmittance (%) PVC-DEH P Average (%) T0 Average (%) T 1 month Average (%) 12 months PET copolymer Yes 64,61 ± 0,66 64,68 ± 0,38 62,60 ± 1,16 PET copolymer No 64,61± 0,66 64,83 ± 0,63 63,44 ± 0,54 PET and PP copolymer Yes 64,61± 0,66 64,07 ± 0,58 63,76 ± 0,67 PET and PP copolymer No 64,61± 0,66 65,21 ± 0,41 64,05 ± 0,62 PET non-woven fabric Yes 64,61± 0,66 62,86 ± 0,49 49,42 ± 1,53 PET non-woven fabric No 64,61± 0,66 59,72 ± 0,66 55,64 ± 0,59

[0113] These tests show that the PET copolymer film can protect the irradiation pouch at least in the short term from the diffusion of plasticizers (DEHP) and other contaminating substances from the packaging bag.

[0114] The protective sleeve made of PET and PP copolymer provides stability of UV transmittance over time.

[0115] However, due to its high porosity, the sleeve made of spun-bonded PET non-woven fabric does not maintain the UV transmittance of the EVA sheath.

Claims

1. Bag system (1) for the treatment of a biological fluid by electromagnetic irradiation, said bag system comprising at least one element consisting of an irradiation bag (2) intended to contain the biological fluid to be irradiated, said irradiation bag (2) being made of a material that is permeable to said electromagnetic radiation, said system comprising one or more other elements selected from the group consisting of at least one storage bag (8) and a tubing (9), at least one of said other elements being made of a polymer material formulated with at least one plasticizer, characterized in that it further comprises at least one protective film (26a, 26b) forming a barrier means to said plasticizer and covering said irradiation bag (2), said protective film (26a, 26b) being made of a gas-barrier polymer material having a permeability to oxygen of less than or equal to 100 cm3 / m2 / 24 h at a temperature of 23°C and a relative humidity of 50%.

2. Bag system according to claim 1, characterized in that the polymer material of the protective film (26a, 26b) is a water vapor barrier polymer material with a permeability to water vapor of less than or equal to 10 g / m2 / 24 h at a temperature of 23°C and a relative humidity of 50%.

3. Bag system according to one of claims 1 or 2, characterized in that the protective film (26a, 26b) is transparent.

4. Bag system according to any of claims 1 to 3, characterized in that the protective film (26a, 26b) comprises at least one layer of polyester or polypropylene.

5. Bag system according to any one of claims 1 to 4, characterized in that it comprises two protective films (26a, 26b) arranged on either side of the irradiation bag (2).

6. Bag system according to claim 5, characterized in that the two protective films (26a, 26b) together form a sleeve with at least one open end in which the irradiation bag (2) is arranged.

7. Bag system according to any one of claims 1 to 6, characterized in that the electromagnetic irradiation treatment is a UV radiation treatment and the irradiation bag is made of a material permeable to UV radiation.

8. Bag system according to any one of claims 1 to 7, characterized in that the irradiation bag (2) is free of photosensitive agent.

9. Bag system according to any one of claims 1 to 8, characterized in that each of said other elements is made from a material or materials formulated without phthalate or terephthalate.

10. Bag system according to claim 9, characterized in that said other element(s) of the bag system comprise one or more elements selected from the group consisting of a storage bag (8), a sampling bag (11), tubing (6, 9, 12, 15), a connector (16), a clamp (18a, 18b, 18c, 18d), a vent (7a, 7b, 17a, 17b) and combinations thereof.

11. Bag system according to one of claims 9 or 10, characterized in that each of said other elements of said bag system is made of a material or materials other than polyvinyl chloride plasticized with di-2-ethylhexyl phthalate or di-2-ethylhexyl terephthalate.

12. Bag system according to any one of claims 9 to 11, characterized in that each of said elements of the bag system is made either of polyvinyl chloride plasticized with a plasticizer selected from the group consisting of a cyclohexanedicarboxylic acid ester, a citrate ester, a trimellitate ester or a mixture thereof, or of a material other than plasticized polyvinyl chloride.

13. Assembly (20) for the treatment of a biological fluid by electromagnetic irradiation comprising a package (21) and a bag system (1) according to any one of claims 1 to 12, characterized in that said bag system (1) is sterilely confined in said package (21).

14. Assembly according to claim 13, characterized in that the package (21) is formed of a porous non-woven sheet and of a transparent film sheet.

15. Use of a film (26a,26b) made of a gas-barrier polymer material having a permeability to oxygen of less than or equal to 100 cm3 / m2 / 24 h at a temperature of 23°C and a relative humidity of 50% as a barrier to releasable plasticizers of polyvinyl chloride for a bag system according to any one of claims 1 to 14.

16. Use of a film according to claim 15, characterized in that the film is made of a water vapor-barrier polymer material having a permeability to water vapor of less than or equal to 10 g / m2 / 24 h at a temperature of 23°C and a relative humidity of 50%.

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