A prefilled syringe having a high gas barrier

Abstract

A prefilled syringe comprising a barrel having a first and a second opening, wherein the first opening is a tip, wherein a plunger stopper is placed through the second opening in the barrel thereby forming a syringe volume and a back space, wherein the syringe volume and the back space are fluidly disconnected and wherein the syringe volume is prefilled with a fluid, wherein the tip is fluidly closed by a sealing, and wherein the second opening is fluidly closed by a lid.

Description

[0001] A Prefilled Syringe Having a High Gas Barrier

[0002] Technical Field of the Invention

[0003] The present invention is located in the field of prefilled syringes, in particular of syringes prefilled with material, preferably pharmaceutical solutions, which are sensitive to oxidation.

[0004] Background of the Invention

[0005] Degradative oxidation of pharmaceuticals may lead to reduced API efficacy and / or creation of unwanted, if not toxic, degradation products and / or precipitates. Hence, it is generally necessary to protect oxygen sensitive pharmaceutical solutions from oxygen to increase their shelf life.

[0006] Some pharmaceuticals need to be injected into the body of a patient or into medicinal systems, using syringes. Furthermore, to enhance sterility, syringes are often provided prefilled and sterilized with a pharmaceutical solution. However, also these solutions may be prone to oxidation as set out above.

[0007] In view of a syringe system, oxygen can be introduced from different sources such as oxygen dissolved in the solution during the weighing and mixing process, oxygen present in the primary headspace of the syringe, and oxygen permeating from the environment or from the secondary headspace, for example provided by packing the syringe in an outer packaging such as a blister or overwrapping bag, if any.

[0008] Furthermore, oxygen can migrate through the barrel, the plunger stopper, and / or the tip cap of the syringe. The tip of a syringe usually has only a very small surface in comparison to the volume of the syringe and is thus considered as being not too problematic in view of oxygen permeation. However, the plunger stopper and the barrel have a bigger diameter, hence surface, and are thus more prone to oxygen migration through said surfaces.

[0009] As a solution, barrels made of glass, which has a very high gas barrier, have been proposed. However, such barrels are brittle. Hence, manufacturers replaced them with plastic barrels containing plastic material, e.g., polypropylene or polyolefins made from cyclic olefins. However, such materials are much more oxygen permeable than glass. The prior art provides the solution of improving the gas barrier properties of such plastic material containing barrels by adding barrier layers or coating (e.g., vinyl alcohol layers or metal oxide coatings). Still, the plunger stoppers are usually made from elastomeric material, as they have to ensure that the syringe is liquid-tightly closed, and the plunger is thus movable in the barrel. However, elastomeric materials usually used for the plunger stoppers have poor barrier properties and cannot be easily exchanged.

[0010] Summary of the Invention

[0011] Coatings on the plunger stoppers can decrease the amount of leaching of chemical components from the elastomeric material into the pharmaceutical solution in the syringe. However, it has been found that they cannot satisfyingly improve the oxygen barrier properties of the plunger stopper.

[0012] To address this problem, prefilled syringes containing oxygen sensitive pharmaceutical solutions are typically packed - after terminal sterilization, if any - into barrier blister packs along with an oxygen absorber and a plunger rod, or in a barrier flow wrap, eventually with the plunger rod preassembled to the plunger stopper. In both cases, a secondary packaging is required to ensure the gas barrier, which adds packaging material and, hence, waste. Furthermore, the volume of the secondary headspace contained in the blister pack or flow-wrap eventually is bigger than the volume contained in the back of the syringe barrel, in particular when rigid blister packs are used to protect and hold the various components in predefined positions (i.e. , by shaping the bottom rigid blister part in a way to provide fixation to said various components). This, again, introduces a certain amount of oxygen, which needs to be further reduced. Otherwise, the oxygen absorber that is typically added to the packaging could already be contaminated with oxygen upon packaging, which again reduces the shelf life of the packaged prefilled syringe. Therefore, typically, the packaging process is carried out under nitrogen to prevent contact between the oxygen absorber and oxygen. This, however, adds additional complexity and costs to the production process of the prefilled syringe. The amount of oxygen in the secondary headspace can also further be reduced by flushing the blister pack with nitrogen before it is sealed.

[0013] It is therefore an object of the present invention to provide a prefilled syringe , preferably containing oxygen sensitive pharmaceutical solutions, which has improved oxygen permeability prevention and therefore provides an improved shelf-life. It is another object of the present invention to provide a prefilled syringe containing oxygen sensitive pharmaceutical solutions, which requires reduced packaging and, hence, waste.

[0014] It has now surprisingly been found that above-mentioned objects can be achieved by a prefilled syringe comprising a barrel having a first and a second opening, wherein the first opening is a tip, wherein a plunger stopper is placed through the second opening in the barrel thereby forming a syringe volume and a back space, wherein the syringe volume and the back space are fluidly disconnected and wherein the syringe volume is prefilled with a fluid, wherein the tip is fluidly closed by a sealing, and wherein the second opening is fluidly closed by a lid.

[0015] It has further surprisingly been found that above-mentioned objects can be achieved by a process for manufacturing a prefilled syringe, the process comprising the steps of filling in a filling step a syringe comprising a barrel having a first and a second opening, and a plunger stopper, sealing in a sealing step the second opening of the barrel with a lid.

[0016] It has further surprisingly been found that above-mentioned objects can be achieved by the use of a prefilled syringe according to the present invention for protecting the fluid from oxidative degradation.

[0017] Brief Description of the Drawings

[0018] Figure 1 shows a schematic view of a prefilled syringe according to the present invention.

[0019] Reference signs

[0020] The following reference signs have been used throughout the description and Figure 1.

[0021] 1 Barrel

[0022] 2 First opening (tip) of the barrel

[0023] 3 Plunger stopper

[0024] 4 Syringe volume

[0025] 5 Back space of the syringe

[0026] 6 Sealing

[0027] 7 Lid

[0028] 8 Oxygen Absorber

[0029] Definitions

[0030] The term "sterile" as used denotes the status of an object having a significantly reduced number of bacteria and / or viruses on its surface to reduce the risk of an infection. In particular, the term "sterile" denotes an object or substance, which has a bioburden load, which is the theoretical probability of a single viable microorganism being present on or in the sterilized unit, of lower than 10'6. The bioburden load can be measured i.e., according to ISO 11737-1 :2018.

[0031] The term "sterilization" as used herein denotes a method to destroy all forms of living microorganisms from a substance. As there is always a certain probability of at least one microorganism to survive such procedure, the aim of sterilization is the reduction of initially present microorganisms or other potential pathogens. Generally, sterilization is accepted to be achieved if the bioburden load of the substance of object to be sterilized is lower than 10'6. The bioburden load can be measured i.e., according to ISO 11737-1 :2018. Sterilization can be achieved using several methods. In one sterilization process the object is heated up to at least 105 °C, preferably 121 °C, to achieve a sterile object. Thereby, the object should not be deformed by the elevated temperature. Preferably, the heating step is performed in an autoclave. In another sterilization process, the object is brought into contact with toxic gases such as a mixture of ethylene oxide and carbon dioxide. Filtration methods are also used to sterilize liquids, i.e., by using membrane filters, Seitz filters, and / or candle filters. Finally, sterilization can be achieved by indirect energy import into or onto the object, e.g., by ultrasonic waves, ultraviolet light, as well as by high energy particles (such as electrons, gamma- or X-rays).

[0032] The term "headspace" as used herein denotes a volume filled with gas defined within or around the syringe. Thereby, it is differentiated between the primary headspace and the secondary headspace.

[0033] The primary headspace is the volume of gas stored in a compartment comprising a medicinal product and / or which may enter in contact with the medicinal product during use (i.e., which may be part of the fluid path) . In the case of a single chamber syringe, the primary headspace is enclosed within the barrel, the tip cap and the plunger stopper. After filling, the primary headspace comprises the gases which were present in the primary container at the time of closing, as well as the gases dissolved in the medicinal product.

[0034] The secondary headspace is usually defined as the volume outside the primary container, i.e., defined by a packaging or wrapping. Usually, syringes are provided within a secondary packaging defining the secondary headspace. In the present invention, the second opening is sealed, thereby defining a further volume from the plunger to the second opening of the barrel, which is not filled by the liquid within the prefilled syringe and is not part of the fluid path during the storage, nor during the use of the syringe. It is therefore considered the back space.

[0035] The term "liquid-tight" as used herein denotes a quality of an object to function as a barrier for a liquid, preferably for a water-based liquid.

[0036] The term "fluidly closed" as used herein denotes a former connection, which has been liquid-tightly closed by another entity. The term "barrier layer1' as used herein denotes a material, which can slow down the process of oxygen permeation. Preferably, it comprises, more preferably consists of, a plastic barrier material, most preferably ethylene-vinyl alcohol (EVOH), or a metal oxide material, most preferably a silicon oxide layer or an aluminum oxide layer.

[0037] The term "barrier label layer1' as used herein denotes a label made of a barrier layer such as an EVOH-comprising or SiOx-comprising film (i.e., barrier), that is wrapped around the barrel to provide the barrier function. As long as said label covers the barrel from the stopper parking position to the barrel end, the gas permeability of the prefilled syringe is strongly reduced. For the tip area, the usage of a barrier label layer becomes more difficult. However, preferably, the label should overlap all barrel components to ensure a complete barrier surrounding. Nevertheless, covering the cylindrical part of the barrel can already significantly increase the barrier.

[0038] The term " oxygen-absorber1' as used herein denotes a material, which reacts with oxygen and oxidizes itself, thereby "trapping" at least a part of the present oxygen.

[0039] The term "oxygen depleted gas" denotes a gas, which has a lower concentration of oxygen than air, preferably no or only trace amounts of oxygen. Hence, preferably, the oxygen depleted gas comprises, preferably consists of, a gas selected from nitrogen, carbon dioxide, a noble gas, or mixtures thereof. Most preferably, the oxygen depleted gas comprises, preferably consists of, nitrogen.

[0040] The term "oxygen sensitive material" as used herein denotes a compound, which reacts at room temperature and under standard conditions with oxygen, whereby the structure of the oxygen sensitive material is modified. Preferably, the oxygen sensitive material is pharmaceutically active, and the pharmaceutical effect is removed or changed upon the change of the structure of the oxygen sensitive material.

[0041] Detailed Description of the Invention

[0042] In the following, the present invention will be described in detail. Thus, the prefilled syringe of the present invention, the use of the prefilled syringe of the present invention, and the process for manufacturing the prefilled syringe of the present invention are described in the following.

[0043] Prefilled syringe

[0044] The present invention relates to a prefilled syringe comprising a barrel (1) having a first and a second opening, wherein the first opening is a tip (2), wherein a plunger stopper (3) is placed through the second opening in the barrel (1) thereby forming a syringe volume (4) and a back space (5), wherein the syringe volume (4) and the back space (5) are fluidly disconnected and wherein the syringe volume (4) is prefilled with a fluid, wherein the tip is fluidly closed by a sealing (6), and wherein the second opening is fluidly closed by a lid (7).

[0045] Thereby, the lid (7) defines the back space (8) of the syringe, which is in particular problematic in view of oxygen permeation. In comparison to the packaged prefilled syringes as disclosed in the prior art, the volume of the back space is significantly reduced. In the packaged prefilled syringes of the prior art the whole volume of the secondary packaging (e.g., blister pack, flow wrap) has to be considered as back space . Therefore, the amount of oxygen present in the back space is considerably larger in the prior art solutions. As an effect thereof, in the prefilled syringe according to the present invention, the amount of oxygen, which potentially could permeate the stopper plunger and reach the solution, is significantly reduced. As a second effect, the amount of material used for packaging is considerably reduced.

[0046] The closing of the second opening by the lid (7) is preferably achieved by thermal welding, preferably by thermally welding a plastic and / or metallic film with a sealing layer to the barrel (1), by gluing, or by physical connection processes, preferably form-fitting or force-fitting.

[0047] Preferably, the sealing (6) is a closure, wherein the closure can be a removable cap or a break-off cap or even a combination thereof. Preferably, the closure is selected from the list consisting of traditional push-on "mushroom" rubber stoppers, threaded rubber stoppers, simple threaded caps, preferably made from plastics, more preferably from polyethylene and / or polypropylene, complex rigid housing with elastomeric insert (such as BD, Gerresheimer, etc.), and break-off parts (such as disclosed WO 2007 / 083034).

[0048] In a preferred embodiment of the present invention, an oxygen absorber (8) is positioned in the back space (5). Generally, the presence of an oxygen absorber (8) anywhere in the back space (5) further reduces the amount of oxygen in the back space (5) and, thus, further reduces the amount of oxygen potentially permeating into the solution. This helps to further extend the shelf life of the prefilled syringe.

[0049] Preferably, the oxygen absorber (8) is attached to the lid (7), preferably attached to the lid (7) by means selected from the list consisting of gluing, welding, sealing, trapping in a cage, bonding, mechanical fitting, and mixtures thereof. The advantage of the oxygen-absorber (8) being attached to the lid (7) is that the lid (7) and the oxygen-absorber (8) can be removed at the same time and using the same action. This, on the other hand, reduces manipulation time and facilitates the usage of the syringe when being applied, i.e. , by a nurse to the patient.

[0050] Generally, the present invention does not depend on the material used for the barrel (1). However, preferably, the material of the barrel (1) comprises a component, preferably consists of a component, wherein the component is selected from glass or a polymer, preferably is a polymer. As discussed above, using glass for the barrel has the advantage of a high gas barrier, but the drawback of high brittleness and thus the tendency of breaking when being dropped. Furthermore, glass has a relatively high density, thereby increasing the weight of the syringe, and also more costly to be processed. Thus, in general, polymers are the preferred choice for the barrel , which have a lower density and are less prone to breaking. More preferably, the polymer is selected from a polypropylene, a cyclic olefin polymer, and a cyclic olefin copolymer.

[0051] The barrel (1) preferably comprises at least one layer selected from the list consisting of a barrier layer, an oxygen absorber layer, and a barrier label layer. This further reduces the gas barrier of a barrel made from a polymer.

[0052] In a preferred embodiment of the invention, the barrier label layer comprises, preferably consists of, a plastic barrier material, most preferably ethylene-vinyl alcohol (EVOH), or a metal oxide material, most preferably a silicon oxide layer or an aluminum oxide layer. The advantage of this embodiment is that the migration of additives from the plastic material of the barrel (1) to the solution can be decreased, preferably depleted.

[0053] Preferably, the barrier layer is not positioned on the outer surface of the barrel (1). This has the advantage that the barrier layer is protected by the material of the barrel (1). Furthermore, barrier layers on the outer surface of the barrel (1) provide the risk of oxygen permeating through non-protected parts of the barrel (1), such as the crosssection of the barrel cylinder.

[0054] Hence, preferably the barrier layer is either embedded into the material of the barrel (1) or positioned on the inner surface of the barrel (1).

[0055] Most preferably, the barrier layer is positioned on the inner surface of the barrel (1).

[0056] In another preferred embodiment of the invention, the barrier layer comprises, preferably consists of, a plastic barrier material, most preferably ethylene-vinyl alcohol (EVOH), or a metal oxide material, most preferably a silicon oxide layer or an aluminum oxide layer. Plastic barrier materials can be easier worked into the barrel by for example coextrusion. Metal oxide layer can be easier to be worked onto the barrel, for example by deposition. The advantage of this embodiment is that the migration of additives from the plastic material of the barrel (1) to the solution can be decreased, preferably depleted.

[0057] Preferably, the barrier layer comprises, preferably consists of, a metal oxide material and is positioned on the inner surface of the barrel (1). The advantage of this embodiment is that the metal oxide layer can be added to the barrel in a facilitated process, particularly in comparison with a process in which the layer is added within the material of the barrel. Furthermore, the glass-like surface offers other benefits in terms of compatibility with the packed solution, particularly in view of lower adhesion and migration. Finally, it protects the layer against scratches.

[0058] In another preferred embodiment of the invention, the oxygen absorber layer comprises, preferably consists of, an oxygen scavenger in a polypropylene matrix, a cyclic olefin polymer matrix, or a cyclic olefin copolymer matrix.

[0059] In a preferred embodiment of the invention, the plunger stopper (3) is made from an elastomeric material, preferably an elastomeric material selected from the list consisting of ethylene propylene diene monomer rubber (EPDM), halobutyl rubber (such as chlorobutyl (CIIR) or bromobutyl (BUR) rubbers), polyisoprene, brominated isobutylene paramethyl-styrene terpolymers (BIMSM), thermoplastic elastomer, preferably styrenic-block copolymers (TPE-S), and thermoplastic polyolefins (TPE-O). While the invention does not depend on the material used in the plunger stopper, the technical effect is most prominent with such stoppers, as they provide a low gas barrier and thus are prone to oxygen permeation.

[0060] A stopper with low gas barrier property is actually even favorable, since the oxygen dissolved in the solution would more rapidly diffuse through the stopper towards the backspace in order to reach equilibrium, in particular when the backspace has been flushed with oxygen depleted gas and / or comprises an oxygen absorber which reduces the amount of oxygen in said backspace, hence reduce its concentration in said solution, resulting in a slower oxidative degradation of said solution and increased shelf-life stability.

[0061] In a preferred embodiment of the present invention, the material of the oxygen absorber (8) is selected from the list consisting of metal-based, preferably iron and / or calcium-based, absorbers, and oxidizable polymers.

[0062] Preferably, the lid (7) comprises, preferably consists of, a multilayer film comprising a metallic layer, a metal oxide layer, and an EVOH layer. Preferably, the lid (7) should have at least the same gas barrier properties as the material used for the barrel (1). The multilayer film is preferably produced by lamination, more preferably colamination, or coextrusion. In case the multilayer film comprises a metal oxide layer, a lamination or colamination process is advantageous. However, if the multilayer film does not comprise a metal oxide layer, but rather an EVOH layer, coextrusion is preferred.

[0063] Preferably, the permeability into the back space (5) through the combined surface of the remaining barrel (1) between the plunger stopper (3) and the lid (7) and of the lid (7) is lower than the permeability through the plunger stopper (3).

[0064] Preferably, the multilayer film has an oxygen transmission rate of lower than 10 cc / (m2*day*atm) at 23°C / 90%rH, more preferably lower than 1 cc / (m2*day*atm) at 23°C / 90%rH, and most preferably lower than 0.1 cc / (m2*day*atm) at 23°C / 90%rH.

[0065] Preferably, the multilayer film has a water vapor transmission rate of lower than 10 g / (cm2*day) at 37.8°C / 100%rH, more preferably lower than 1 g / (cm2*day) at 37.8°C / 100%rH, and most preferably lower than 0.1 g / (cm2*day) at 37.8°C / 100%rH.

[0066] Preferably, the multilayer film has a thickness of lower than 250 pm, preferably lower than 150 pm, and most preferably lower than 100 pm.

[0067] Most preferably, the multilayer film is selected from the group of films consisting of V97d (PP / EVOH / PP, 200 pm), having an oxygen transmission rate of lower than or equal to 0.2 cc / (m2*day*bar) at 23°C / 50%rH) and a water vapor transmission rate of lower than or equal to 2.5 g / (m2*day) @ 38°C / 100%rH) and DNP SF-T-170 (PP+SiOx, 170 pm) having an oxygen transmission rate of lower than or equal to

[0068] 1 .5 cc / (m2*day*bar) at 23°C / 50%rH) and a water vapor transmission rate of lower than or equal to 4 g / (m2*day) at 38°C / 100%rH).

[0069] In a preferred embodiment of the present invention, the back space (5) is filled with an oxygen depleted gas. This helps further reducing the amount of oxygen, which could permeate into the solution.

[0070] Usually, the prefilled syringe is prefilled with a fluid. More preferably, the fluid comprises an oxygen sensitive material. Most preferably, the oxygen sensitive material is a pharmaceutically active material.

[0071] Preferably, the prefilled syringe is intended to be used in situation, which could lead to infections of a patient. Hence, such an application requires measures for preventing such infections. Therefore, preferably, the prefilled syringe has been subjected to sterilization. Most preferably, the prefilled syringe is sterile. Process for manufacturing the prefilled syringe

[0072] The present invention further relates to a process for manufacturing a prefilled syringe, the process comprising the steps of: filling in a filling step a syringe comprising a barrel (1) and a plunger stopper (3) wherein the barrel (1) has a first and a second opening, and sealing the first opening, sealing in a sealing step the second opening of the barrel (1) with a lid (7).

[0073] With this process a prefilled syringe can be produced, which has a smaller back space (5) in comparison to the packaged prefilled syringes as disclosed in the prior art. In the packaged prefilled syringes of the prior art the whole volume of the packaging has to be considered as back space (5). Therefore, the amount of oxygen present in the back space is considerably larger in the prior art solutions. As an effect thereof, in the prefilled syringe according to the present invention, the amount of oxygen, wh ich potentially could permeate the stopper plunger and reach the solution, is significantly reduced. As a second effect, the amount of material used for packaging is considerably reduced. It should be understood that the filling step, which comprises the filling of the barrel and the sealing of the first opening, in its most general embodiment does not define the order of these two sub-steps. Hence, the sealing of the first opening can occur before the filling and vice versa.

[0074] In a preferred embodiment of the present invention, in the process the filling step comprises the step of: either sealing in a tip sealing step the first opening, preferably tip (1), preferably with a cap (4), filling in a stopper filling step the barrel (1) through the second opening, with a fluid, inserting in a stopper inserting step a plunger stopper (3) through the second opening of the barrel (1), thereby forming a syringe volume (4) filled with the fluid and a back space (5), or inserting in a stopper inserting step a plunger stopper (3) through the second opening of the barrel (1), thereby forming a syringe volume (5) and a back space (5), filling in a tip filling step the barrel (1) through the first opening with a fluid, sealing in a tip sealing step the first opening, preferably tip (1), preferably with a cap (4).

[0075] Preferably, the tip sealing step includes sealing the first opening, preferably tip (1), using a closure. Preferably, the closure can be a removable cap or a break-off cap or even a combination thereof. Preferably, the closure is selected from the list consisting of traditional push-on "mushroom" rubber stoppers, threaded rubber stoppers, simple threaded caps, preferably made from plastics, more preferably from polyethylene and / or polypropylene, and complex rigid housing with elastomeric insert (such as BD, Gerresheimer, etc.). In case of the first alternative, i.e. , in the alternative, in which the tip sealing step precedes the stopper filling step, the tip sealing step could also be achieved by providing a barrel (1) with a closed tip, which can include break-off parts (such as disclosed WO 2007 / 083034). Hence, the first alternative has the advantage that it provides a possibility for filling a syringe having a tip, which cannot be reversibly opened or closed.

[0076] On the other hand, the second alternative has the advantage that it assures that the prefilled syringe is filled with the least possible gas intake.

[0077] In an even more preferred embodiment of the present invention, the process further comprises, subsequent to the filling step and prior to the sealing step, the step of positioning in an absorber positioning step an oxygen absorber (8) through the second opening of the barrel (1).

[0078] This process allows for the preparation of a prefilled syringe according to the present invention having an oxygen absorber (8) positioned in the back space (5) allowing for further decrease of oxygen being present in the back space (5). Even more preferably, the absorber (8) is attached to the lid (7) prior to the absorber positioning step. This embodiment has the advantage of a facilitated positioning step.

[0079] Preferably, the oxygen absorber (8) is attached to the lid (7) by means selected from the list consisting of gluing, welding, sealing, trapping in a cage, bonding, mechanical fitting, and mixtures thereof. The advantage of this preferred embodiment is that the process has been simplified and thus requires less time resources and costs. Furthermore, in the produced prefilled syringe, lid (7) and the oxygen-absorber (8) can be removed at the same time and using the same action.

[0080] In another preferred embodiment of the present invention, the process further comprises prior to the sealing step the step of purging in a purging step the barrel (1) through the second opening with an oxygen depleted gas, preferably nitrogen. This allows for additional removal of oxygen in the back space (5). For this embodiment having this effect, an oxygen absorber (5) does not necessarily need to be positioned in the back space (5). However, the combination of the absorber positioning step or the combined sealing step and the purging step is especially advantageous, as the oxygen depleting effects of both steps are combined.

[0081] In another preferred embodiment of the present invention, the process further comprises subsequent to the filling step and prior to the sealing step the step of adding in an aqueous solution adding step an aqueous solution in the barrel (1) through the second opening.

[0082] Preferably, the aqueous solution is selected from water and alcohol, preferably ethanol, comprising water. The aqueous solution improves the sterilizing effect in the back space, as wet heat is more sufficient for that purpose than dry heat.

[0083] Preferably, the process according to the present invention comprises as a final process step the step of sterilizing the prefilled syringe.

[0084] Use of the prefilled syringe

[0085] Furthermore, the present invention provides the use of the prefilled syringe according to the present invention for protecting the fluid from oxidative degradation. This effect is in particular achieved by the sealing and thus reducing of the volume of the back space (5). However, further measures can improve this effect, in particular the oxygen absorber (8) positioned in the back space (5) of the prefilled syringe and / or the oxygen depleted gas in the back space (5) of the prefilled syringe.

Claims

Claims1. A prefilled syringe comprising a barrel (1) having a first and a second opening, wherein the first opening is a tip (2), wherein a plunger stopper (3) is placed, through the second opening, into the barrel (1) thereby forming a syringe volume (4) and a back space (5), wherein the syringe volume (4) and the back space (5) are fluidly disconnected and wherein the syringe volume (4) is prefilled with a fluid, wherein the tip is fluidly closed by a sealing (6), and wherein the second opening is fluidly closed by a lid (7)2. The prefilled syringe according to claim 1 , wherein an oxygen absorber (8) is positioned in the back space (5).

3. The prefilled syringe according to claims 1 or 2, wherein the oxygen absorber (8) is attached to the lid (7), preferably attached to the lid (7) by means selected from the list consisting of gluing, welding, sealing, trapping in a cage, bonding, mechanical fitting, and mixtures thereof.

4. The prefilled syringe according to any of the preceding claims, wherein the material of the barrel comprises a component, preferably consists of a component, wherein the component is selected from glass or a polymer, preferably a polymer more preferably a polymer selected from a polypropylene, a cyclic olefin polymer, and a cyclic olefin copolymer.

5. The prefilled syringe according to any of the preceding claims, wherein the barrel (1) comprises at least one layer selected from the list consisting of a barrier layer, an oxygen absorber layer, and a barrier label layer.

6. The prefilled syringe according to claim 5, wherein the barrier layer or the barrier label layer comprises, preferably consists of, a plastic barrier material, most preferably ethylene-vinyl alcohol (EVOH), or a metal oxide material, most preferably a silicon oxide layer or an aluminum oxide layer.

7. The prefilled syringe according to claims 5 or 6, wherein the barrier layer is not positioned on the outer surface of the barrel (1), wherein the barrier layer is preferably either embedded into the material of the barrel (1) or positioned on the inner surface of the barrel (1), wherein the barrier layer is most preferably positioned on the inner surface of the barrel (1).

8. The prefilled syringe according to any of the preceding claims, wherein the plunger stopper (3) is made from an elastomeric material, preferably anelastomeric material selected from the list consisting of ethylene propylene diene monomer rubber (EPDM), halobutyl rubber (such as chlorobutyl (Cl I R) or bromobutyl (BUR) rubbers), polyisoprene, brominated isobutylene paramethylstyrene terpolymers (BIMSM), thermoplastic elastomer, preferably styrenic-block copolymers (TPE-S), and thermoplastic polyolefins (TPE-O).

9. The prefilled syringe according to any of the preceding claims, wherein the material of the oxygen absorber (3) is selected from the list consisting of metalbased, preferably iron and / or calcium-based, absorbers, and oxidizable polymers.

10. The prefilled syringe according to any of the preceding claims, wherein the material of the lid (7) is selected from the list consisting of a multilayer film comprising a metallic layer, a metal oxide layer, and an EVOH layer.

11. A process for manufacturing a prefilled syringe, the process comprising the steps of: filling in a filling step a syringe comprising a barrel (1) and a plunger stopper (3), wherein the barrel (1) has a first and a second opening, and sealing the first opening, sealing in a sealing step the second opening of the barrel (1) with a lid (7).

12. The process according to claim 11 , wherein the filling step comprises the step of: either sealing in a tip sealing step the first opening, preferably tip (1), preferably with a cap (4), filling in a stopper filling step the barrel (1) through the second opening, with a fluid, inserting in a stopper inserting step a plunger stopper (3) through the second opening of the barrel (1), thereby forming a syringe volume (4) filled with the fluid and a back space (5), or inserting in a stopper inserting step a plunger stopper (3) through the second opening of the barrel (1), thereby forming a syringe volume (5) and a back space (5), filling in a tip filling step the barrel (1) through the first opening, with a fluid,sealing in a tip sealing step the first opening, preferably tip (1), preferably with a cap (4).

13. The process according to claims 11 or 12, wherein the process further comprises, subsequent to the filling step and prior to the sealing step, the step of positioning in an absorber positioning step an oxygen absorber (8) through the second opening of the barrel (1).

14. The process according to claim 13, wherein the absorber (8) is attached to the lid (7) prior to the absorber positioning step.

15. Use of a prefilled syringe according to any of the preceding claims 1 to 10 for protecting the fluid from oxidative degradation.

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